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Investigation of apoptotic effects of Cucurbitacin D, I, and E mediated by Bax/Bcl-xL, caspase-3/9, and oxidative stress modulators in HepG2 cell line Drug Dev. Res. (IF 3.8) Pub Date : 2024-03-18 Muhammed Mehdi Üremiş, Yusuf Türköz, Nuray Üremiş
Cucurbitacins, natural compounds highly abundant in the Cucurbitaceae plant family, are characterized by their anticancer, anti-inflammatory, and hepatoprotective properties. These compounds have potential as therapeutic agents in the treatment of liver cancer. This study investigated the association of cucurbitacin D, I, and E (CuD, CuI, and CuE) with the caspase cascade, Bcl-2 family, and oxidative
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Improving therapeutic potential in breast cancer via histone deacetylase inhibitor loaded nanofibrils Drug Dev. Res. (IF 3.8) Pub Date : 2024-03-16 Praveetha Senthilkumar, Bhaskar Gogoi, Swati Smita Dhan, Ramesh Subramani, Charumathi Pushparaj, Ayyavu Mahesh
Epigenetic modifications play a significant role in cancer progression, making them potential targets for therapy. Histone deacetylase inhibitors have shown promise in inhibiting cancer cell growth, including in breast cancer (BC). In this research, we examined the potential of using suberoyl anilide hydroxamic acid (SAHA)‐loaded β‐lg nanofibrils as a drug delivery system for triple‐negative BC cell
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Xanthones with multiple roles against diabetes: their synthesis, structure‐activity relationship, and mechanism studies Drug Dev. Res. (IF 3.8) Pub Date : 2024-03-14 Youhong Ke, Qinfang Xu, Jianling Hu, Jianrun Zhang, Shijian Chen, Zhijun Liu, Shuling Peng, Chao Zhang, Zhenqiang Chen, Heru Chen
A four‐step synthetic process has been developed to prepare 1,3,5,8‐tetrahydroxyxanthone (2a) and its isomer 1,3,7,8‐tetrahydroxyxanthone (2b). 25 more xanthones were also synthesized by a modified scheme. Xanthone 2a was identified as the most active inhibitor against both α‐glucosidase and aldose reductase (ALR2), with IC50 values of 7.8 ± 0.5 μM and 63.2 ± 0.6 nM, respectively, which was far active
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Neutrophil hitchhiking: Riding the drug delivery wave to treat diseases Drug Dev. Res. (IF 3.8) Pub Date : 2024-03-13 Menghui Wang, Zhenhua Jin, Haoyu Huang, Xifu Cheng, Qin Zhang, Ying Tang, Xiaoping Zhu, Zhen Zong, Hui Li, Zhikun Ning
Neutrophils are a crucial component of the innate immune system and play a pivotal role in various physiological processes. From a physical perspective, hitchhiking is considered a phenomenon of efficient transportation. The combination of neutrophils and hitchhikers has given rise to effective delivery systems both in vivo and in vitro, thus neutrophils hitchhiking become a novel approach to disease
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Protective effect of thymoquinone nanoemulsion in reducing the cardiotoxic effect of 5‐fluorouracil in rats Drug Dev. Res. (IF 3.8) Pub Date : 2024-03-09 Bardia Karim, Motahare Arabameri, Fatemeh Alimoradi, Razieh Mansoori, Ali A. Moghadamnia, Sohrab Kazemi, Seyed M. Hosseini
5‐Fluorouracil (5‐FU), which is one of the most widely used chemotherapy drugs, has various side effects on the heart. Thymoquinone (TMQ), the main bioactive component of Nigella sativa, has antioxidant and protective effects against toxicity. In this study, we investigated the protective effect of thymoquinone against cardiotoxicity caused by 5‐FU in vitro and in vivo models. H9C2 cells were exposed
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Hypoxia expedites the progression of papillary thyroid carcinoma by promoting the CPT1A‐mediated fatty acid oxidative pathway Drug Dev. Res. (IF 3.8) Pub Date : 2024-03-07 Zhou Liang, Hongsheng He, Bing Zhang, Zhentian Kai, Liang Zong
Hypoxia has been reported to promote the proliferation and migration of thyroid cancer, while the special mechanism was still unclear. HIF‐1α/carnitine palmitoyl‐transferase 1A (CPT1A) was found to be associated with papillary thyroid carcinoma (PTC) but the biological role of CPT1A in PTC was not explored. The effects of hypoxia and carnitine palmitoyl‐transferase 1A (CPT1A) expression on PTC cells
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Deciphering chemoresistance in osteosarcoma: Unveiling regulatory mechanisms and function through the lens of noncoding RNA Drug Dev. Res. (IF 3.8) Pub Date : 2024-03-06 Hefen Chen, Zhujun Gong, Hong Zhou, Yong Han
Osteosarcoma (OS) is a primary malignant bone tumor and is prevalent in children, adolescents, and elderly individuals. It has the characteristics of high invasion and metastasis. Neoadjuvant chemotherapy combined with surgical resection is the most commonly used treatment for OS. However, the efficacy of OS is considerably diminished by chemotherapy resistance. In recent years, noncoding RNAs (ncRNAs)
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Design, synthesis, in silico, and in vitro evaluation of novel benzyloxybenzene substituted (S)‐α‐amino amide derivatives as cholinesterases and monoaminoxidases inhibitor Drug Dev. Res. (IF 3.8) Pub Date : 2024-03-06 Akın Akıncıoğlu
In this study, a series of novel benzyloxybenzene substituted (S)‐α‐amino acid methyl esters and their amide derivatives were synthesized and evaluated for their inhibitory actions against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), monoamine oxidase A (MAO‐A), and monoamine oxidase B (MAO‐B). The synthetic strategy was based on starting from benzyl bromide (5) and 4‐hydroxybenzaldehyde
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Berberine attenuates inflammation and oxidative stress and modulates lymphocyte E‐NTPDase in acute hyperlipidemia Drug Dev. Res. (IF 3.8) Pub Date : 2024-03-01 Reem S. Alruhaimi, Maisa Siddiq Abduh, Ahmad F. Ahmeda, Albandari Bin‐Ammar, Emadeldin M. Kamel, Emad H. M. Hassanein, Chen Li, Ayman M. Mahmoud
Hyperlipidemia is a common clinically encountered health condition worldwide that promotes the development and progression of cardiovascular diseases, including atherosclerosis. Berberine (BBR) is a natural product with acknowledged anti‐inflammatory, antioxidant, and metabolic effects. This study evaluated the effect of BBR on lipid alterations, oxidative stress, and inflammatory response in rats
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Exploring new quinazolin‐4(3H)‐one derivatives as CDK2 inhibitors: Design, synthesis, and anticancer evaluation Drug Dev. Res. (IF 3.8) Pub Date : 2024-02-29 Basant T. Ibrahim, Heba Abdelrasheed Allam, Nehad M. El‐Dydamony, Marwa A. Fouad, Eman R. Mohammed
In the present work, five series of new 2,3‐disubstituted quinazolin‐4(3H)‐ones 4a–c, 5a–d, 6a–g, 7a,b, and 9a–c were designed, synthesized, and screened in vitro for their cytotoxic activity against 60 cancer cell lines by the National Cancer Institute, USA. Five candidates 4c, 6a, 6b, 6d, and 6g revealed promising cytotoxicity with significant percentage growth inhibition in the range of 81.98%–96
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The current perspective and opportunities of small nucleic acid‐based therapeutics Drug Dev. Res. (IF 3.8) Pub Date : 2024-02-27 Yang Chen, Yang Li, Chao Li, Dandan Zhang, Yuheng Liu, Jingjing Zhang, Shan Guan, Xiaoyan Ding, Qin Xiao
Compared to traditional small molecule and antibody drugs, RNA‐based drugs offer a simple design, short research and development cycles, high specificity, broad treatment fields, and long‐term efficacy. As a result, RNA‐based drugs are extensively used to treat genetic diseases, tumors, viral infections, and other illnesses, suggesting that they have the potential to become the third‐largest drug class
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Network pharmacology analysis and experimental verification of the antitumor effect and molecular mechanism of isocryptomerin on HepG2 cells Drug Dev. Res. (IF 3.8) Pub Date : 2024-02-24 Jing‐Long Cao, Shu‐Mei Li, Yan‐Jun Tang, Wen‐Shuang Hou, An‐Qi Wang, Tian‐Zhu Li, Cheng‐Hao Jin
Isocryptomerin (ISO) is a flavonoid isolated from the natural medicine Selaginellae Herba, which has various pharmacological activities. This study investigated the antitumor effect and underlying molecular mechanism of ISO on hepatocellular carcinoma (HCC) HepG2 cells. The cell viability assay revealed that ISO has a considerable killing effect on HCC cell lines. The apoptosis assay showed that ISO
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BAER‐101, a selective potentiator of α2‐ and α3‐containing GABAA receptors, fully suppresses spontaneous cortical spike‐wave discharges in Genetic Absence Epilepsy Rats from Strasbourg (GAERS) Drug Dev. Res. (IF 3.8) Pub Date : 2024-02-21 Alexandra MacLean, Amy S. Chappell, Jay Kranzler, Alexis Evrard, Hugo Monchal, Corinne Roucard
BAER‐101 (formerly AZD7325) is a selective partial potentiator of α2/3‐containing γ‐amino‐butyric acid A receptors (GABAARs) and produces minimal sedation and dizziness. Antiseizure effects in models of Dravet and Fragile X Syndromes have been published. BAER‐101 has been administered to over 700 healthy human volunteers and patients where it was found to be safe and well tolerated. To test the extent
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Piquing artificial intelligence towards drug discovery: Tools, techniques, and applications Drug Dev. Res. (IF 3.8) Pub Date : 2024-02-20 Peter Chinedu Agu, Chidiebere Nwiboko Obulose
The purpose of this study was to discuss how artificial intelligence (AI) methods have affected the field of drug development. It looks at how AI models and data resources are reshaping the drug development process by offering more affordable and expedient options to conventional approaches. The paper opens with an overview of well‐known information sources for drug development. The discussion then
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Synthesis, characterization, molecular modeling studies, and biological evaluation of metal piroxicam complexes (M = Ni(II), Pt(IV), Pd(II), Ag(I)) as antibacterial and anticancer agents Drug Dev. Res. (IF 3.8) Pub Date : 2024-02-14 Aya M. Soliman, Ahmed M. K. El-sagheir, Momen M. Thabet, Ahmed Faried Abdel Hakiem, Ahmed S. Aboraia
Four piroxicam metal complexes; NiL2, PtL2, PdL2, and AgL were synthesized and characterized by different techniques with enhanced antibacterial and anticancer activity. Regarding in vitro antimicrobial activity, complex NiL2 displayed potent antibacterial effect against Escherichia coli and Pseudomonas aeruginosa that was 1.9-folds higher than piroxicam (minimum inhibitory concentration [MIC] = 31
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Bazedoxifene analogs as potential WDHD1 degraders and antitumor agents: Synthesis, evaluation and molecular dynamics simulation studies Drug Dev. Res. (IF 3.8) Pub Date : 2024-02-05 Leyuan Chen, Gaiting Liu, Fancui Meng, Yu shi, Zhennan Fang, Zhenyu Peng, Manjiang Wang, Wenfeng Gou, Wenbin Hou, Yiliang Li
DNA repair is strongly associated with tumor resistance to radiotherapy and chemotherapy. WD repeat and HMG-box DNA binding protein 1 (WDHD1) is a key adaptor for homologous recombination repair of DNA, and its overexpression is relevant to the poor prognosis of many tumor patients. We previously have identified and validated bazedoxifene (BZA), which had 60% inhibitory rate on WDHD1 in MCF7 cells
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N-Substituted piperazine-coupled imidazo[2,1-b]thiazoles as inhibitors of Mycobacterium tuberculosis: Synthesis, evaluation, and docking studies Drug Dev. Res. (IF 3.8) Pub Date : 2024-01-30 Nagaraju Chirra, Naga Pranathi Abburi, Estharla Madhu Rekha, Ravi kumar Pedapati, Rakesh Kumar Bollikanda, Manikanta Murahari, Dharmarajan Sriram, Balasubramanian Sridhar, Srinivas Kantevari
An innovative series of N-substituted piperazine-linked imidazothiazole derivatives 7(a–x) were synthesized, and their antitubercular effectiveness was evaluated. A three-step reaction sequence involving the condensation of 1,3-dichloroacetone and thiourea, coupling with substituted piperazines to give the intermediates 5(a–d) and cyclization with substituted α-bromoacetophenones produced the desired
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Tri-substituted 1,3,5-triazine-based analogs as effective HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs): A systematic review Drug Dev. Res. (IF 3.8) Pub Date : 2024-02-01 Zebabanu Khalifa, Amit B. Patel
Non-nucleoside reverse transcriptase inhibitors (NNRTIs) have significantly impacted the HIV-1 wild-type due to their high specificity and superior potency. As well as different combinations of NNRTIs have been used on clinically approved combining highly active antiretroviral therapy (HAART) to resist the growth of HIV-1 and decrease the mortality rate of HIV/AIDS. Although the feeble strength against
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2-Thioxo-3,4-dihydropyrimidine and thiourea endowed with sulfonamide moieties as dual EGFRT790M and VEGFR-2 inhibitors: Design, synthesis, docking, and anticancer evaluations Drug Dev. Res. (IF 3.8) Pub Date : 2024-01-27 Mohamed S. A. El-Gaby, Mohamed A. M. Abdel Reheim, Zuhir S. M. Akrim, Bassem H. Naguib, Nashwa M. Saleh, Abu Bakr A. A. M. El-Adasy, Khaled El-Adl, Samy Mohamady
The effectiveness of a new series of thiopyrimidine and thiourea containing sulfonamides moieties was tested on HCT-116, MCF-7, HepG2, and A549. HepG2 cell line was the one that all the new derivatives affected the most. The greatest potent compounds against the four HepG2, HCT116, MCF-7, and A549 cell lines were 8f and 8g with IC50 = 4.13, 6.64, 5.74, 6.85 µM and 4.09, 4.36, 4.22, 7.25 µM correspondingly
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Combined chemotherapy of zoledronic acid and pamidronate in the treatment of bone metastases from nonsmall cell lung cancer and the effects on pain stress and bone metabolic indices Drug Dev. Res. (IF 3.8) Pub Date : 2024-01-24 Kun Huang, Xiao Tang, Fang Tang
We conducted this paper to decipher the efficacy of the combined chemotherapy of zoledronic acid and pamidronate in treating bone metastases from nonsmall cell lung cancer (NSCLC) and the effects on pain stress and bone metabolic indices.
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Dendrobine regulates STAT3 to attenuate mitochondrial dysfunction and senescence in vascular endothelial cells triggered by oxidized low-density lipoprotein Drug Dev. Res. (IF 3.8) Pub Date : 2024-01-27 Jia Xia, Jingyi Chen, Xinyue Xing, Jing Meng, Xiaoying Song, Danfei Lou
Our previous studies have highlighted the potential therapeutic efficacy of dendrobine, an alkaloid, in atherosclerosis (AS), nevertheless, the underlying mechanism remains unclear. This study employs a combination of network pharmacology and in vitro experiments to explore the regulatory pathways involved. Through network pharmacology, the biological function for intersection targets between dendrobine
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FGF12 restrains mitochondria-dependent ferroptosis in doxorubicin-induced cardiomyocytes through the activation of FGFR1/AMPK/NRF2 signaling Drug Dev. Res. (IF 3.8) Pub Date : 2024-01-23 Ge Tian, Jing Li, Wenjie Wang, Lina Zhou
Fibroblast growth factor-12 (FGF12) has been reported to play important role in regulating heart diseases. We aimed to explore the role of FGF12 in doxorubicin (DOX)-induced myocardial injury. DOX-induced mice and DOX-induced HL-1 cells were used as the myocardial injury in vivo and in vitro. Then, FGF12, Anp, Bnp, and Myh7 expression was detected. The pathological injury in myocardium tissue was observed
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Development and evaluation of multi-functionalized sialic acid conjugated asiatic acid nanoconstruct to mitigate cognitive deficits in Alzheimer's disease Drug Dev. Res. (IF 3.8) Pub Date : 2024-01-19 Tripti Halder, Bijit Saha, Namdev Dhas, Sanjeev Acharya, Niyati Acharya
Sialic acid (SA) serves a critical role in neuronal repair and cognitive functions. SA is a nine-carbon carboxylated sugar with a glycoconjugate cap that acts as a ligand and surface decoration with SA facilitates delivery to the target site. The present research aimed to develop SA surface modified AA nanostructured lipid carrier (NLCs) with carbodiimide conjugation method. Sterylamine, poloxamer
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Design and synthesis of vancomycin-functionalized ZnFe2O4 nanoparticles as an effective antibacterial agent against methicillin-resistant Staphylococcus aureus Drug Dev. Res. (IF 3.8) Pub Date : 2024-01-18 Minoo Akbari, Ali Hossein Rezayan, Hossein Rastegar, Mahmoud Alebouyeh, Mohammad Yahyaei
The emergence of antibiotic-resistant bacterial infections is a principal threat to global health. Functionalization of nanomaterial with antibiotics is known as a useful method for increasing the effectiveness of existing antibiotics. In this study, vancomycin-functionalized ZnFe2O4 nanocomposite (ZnFe2O4@Cell@APTES@Van) was synthesized, and its functional groups and particle size were characterized
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Costunolide attenuates high-fat diet-induced inflammation and oxidative stress in non-alcoholic fatty liver disease Drug Dev. Res. (IF 3.8) Pub Date : 2024-01-16 Jiong Wang, Bo Jin, Yanghao Chen, Yi Chen, Wei Zuo, Lijiang Huang, Jianjun Lin, Yongsheng Jiang, Longteng Xie, Xiang Lian, Yi Wang
Non-alcoholic fatty liver disease (NAFLD) is a progressive disease that can further evolve towards liver fibrosis and hepatocellular carcinoma in the end stage. Costunolide (Cos) is a natural sesquiterpene lactone that exhibits both anti-inflammatory and antioxidant properties. However, the therapeutic effect of Cos on NAFLD is not clear. In this study, we explored the potential protective effect and
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Drug upgrade: A complete methodology from old drug to new chemical entities using Nematic Protein Organization Technique Drug Dev. Res. (IF 3.8) Pub Date : 2024-01-16 Judith Eschbach, Alain Wagner, Corinne Beahr, Akkiz Bekel, Anne-Sophie Korganow, Angelique Quartier, Jean-Christophe Peter, Pierre Eftekhari
Drug repurposing is used to propose new therapeutic perspectives. Here, we introduce “Drug Upgrade”, that is, characterizing the mode of action of an old drug to generate new chemical entities and new therapeutics. We proposed a novel methodology covering target identification to pharmacology validation. As an old drug, we chose hydroxychloroquine (HCQ) for its well-documented clinical efficacy in
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Proteolysis-targeting chimeras in antiviral therapy: Leveraging influenza virus and exosome-mediated delivery for targeted protein degradation and therapeutic advancements Drug Dev. Res. (IF 3.8) Pub Date : 2024-01-09 Nobendu Mukerjee, Swastika Maitra, Rohit Sharma
CONFLICT OF INTEREST STATEMENT The authors declare no conflict of interest.
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Mechanism of gambogic acid repressing invasion and metastasis of colorectal cancer by regulating macrophage polarization via tumor cell-derived extracellular vesicle-shuttled miR-21 Drug Dev. Res. (IF 3.8) Pub Date : 2024-01-04 You Li, Wenqi Liao, Wei Huang, Fenglin Liu, Lin Ma, Xiaoping Qian
Colorectal cancer (CRC) is a major cause of mortality and morbidity. Gambogic acid (GA) is a promising antitumor drug for treating CRC. We aimed to elucidate its mechanism in CRC invasion/metastasis via tumor cell-derived extracellular vesicle (EV)-carried miR-21. Nude mice peritoneal carcinomatosis (PC) model was subjected to GA treatment liver collection, followed by observation/counting of metastatic
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AKR1C3 silencing inhibits autophagy-dependent glycolysis in thyroid cancer cells by inactivating ERK signaling Drug Dev. Res. (IF 3.8) Pub Date : 2024-01-04 Ying Gao, Weijie Tao, Shoujun Wang, Ran Duan, Zhendong Zhang
Thyroid cancer is a highly differentiated and poorly malignant tumor. Interfering with glycolysis has become an effective means of controlling cancer progression and autophagy is negatively correlated with glycolysis. Aldo-keto reductase family 1 member C3 (AKR1C3) has been demonstrated to be highly expressed in thyroid cancer tissue and the higher AKR1C3 expression predicted the worse prognosis. We
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CALCRL knockdown suppresses cancer stemness and chemoresistance in acute myeloid leukemia with FLT3-ITD and DNM3TA-R882 double mutations Drug Dev. Res. (IF 3.8) Pub Date : 2023-12-22 Shanhao Tang, Huiling Zhu, Lixia Sheng, Qitian Mu, Yi Wang, Kaihong Xu, Miao Zhou, Zhijuan Xu, An Wu, Guifang Ouyang
Acute myeloid leukemia (AML) patients with FLT3 internal tandem duplication (FLT3-ITD) and DNA methyltransferase 3A (DNMT3A) R882 double mutations had a worse prognosis compared with AML with FLT3-ITD or DNMT3A R882 single mutation. This study was designed to explore the specific role of Calcitonin Receptor Like (CALCRL) in AML with FLT3-ITD and DNMT3A R882 double mutations. MOLM13 cells were transduced
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Everolimus inhibits hepatoblastoma by inducing autophagy-dependent ferroptosis Drug Dev. Res. (IF 3.8) Pub Date : 2023-12-22 Haijin Huang, Jinlong Yan, Xianyun Xu, Yanping Feng, Haijin Liu, Jianping Liu, Mingfeng Xie, Leifeng Chen, Deng Xiang, Wei Peng, Linshan Zeng, Yong Zeng, Feng Chen, Shouhua Zhang, Qian Liu
Everolimus, a known inhibitor of the mammalian target of rapamycin (mTOR), has shown uncertain efficacy in treating hepatoblastoma. This study delves into the potential anti-hepatoblastoma properties of everolimus and its intricate relationship with autophagy and ferroptosis, both in vitro and in vivo. In vivo, tumor tissue from hepatoblastoma patient and human hepatoblastoma cell line HuH-6 were xenografted
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Comprehensive characterization and preclinical assessment of an imidazopyridine-based anticancer lead molecule Drug Dev. Res. (IF 3.8) Pub Date : 2023-12-12 Ratik Ramesh Bulbule, Tarang Jadav, Niraj Rajput, Rudradip Das, Deep Rohan Chatterjee, Amit Shard, Pinaki Sengupta
Imidazopyridine scaffold holds significant pharmacological importance in the treatment of cancer. An in-house synthesized imidazopyridine-based molecule was found to have promising anticancer activity against breast cancer, lung cancer, and colon cancer. The molecule is an inhibitor of pyruvate kinase M2, the enzyme that elevates tumor growth, metastasis and chemoresistance by directly controlling
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Exploring the potential of radiolabeled duramycin as an infection imaging probe Drug Dev. Res. (IF 3.8) Pub Date : 2023-12-11 Anuj Kumar, Jyotsna Bhatt Mitra, Elina Khatoon, Aparna Pramanik, Rohit K. Sharma, Ashok Chandak, Sutapa Rakshit, Archana Mukherjee
The continuous pursuit of designing an ideal infection imaging agent is a crucial and ongoing endeavor in the field of biomedical research. Duramycin, an antimicrobial peptide exerts its antimicrobial action on bacteria by specific recognition of phosphatidylethanolamine (PE) moiety present on most bacterial membranes, particularly Escherichia coli (E. coli). E. coli membranes contain more than 60%
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Covalent inhibitors: An ambitious approach for the discovery of newer oncotherapeutics Drug Dev. Res. (IF 3.8) Pub Date : 2023-12-06 Rameshwar S. Cheke, Prashant S. Kharkar
Covalent inhibitors have been used to treat several diseases for over a century. However, strategic approaches for the rational design of covalent drugs have taken a definitive shape in recent times. Since the first appearance of covalent inhibitors in the late 18th century, the field has grown tremendously and around 30% of marketed drugs are covalent inhibitors especially, for oncology indications
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68Ga-labeled, imatinib encapsulated, theranostic liposomes: Formulation, characterization, and in vitro evaluation of anticancer activity Drug Dev. Res. (IF 3.8) Pub Date : 2023-11-27 Merve Karpuz, Emre Ozgenc, Ezgi Oner, Evren Atlihan-Gundogdu, Zeynep Burak
Cancer is still a global health problem. Among cancer types, breast cancer is the most frequently diagnosed one, and it causes a high mortality rate if not diagnosed in the early stages. In our study, imatinib encapsulated, nanosized, neutral/cationic liposome formulations were prepared as theranostic agents for breast cancer. After the characterization studies in which all liposomes exhibited proper
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Novel sulfonamide-phosphonate conjugates as carbonic anhydrase isozymes inhibitors Drug Dev. Res. (IF 3.8) Pub Date : 2023-11-23 Mohamed S. Bekheit, Eman Sabry, Hanan A. Mohamed, Ewies F. Ewies, Benson M. Kariuki, Marwa A. Fouad, Daniela Vullo, Claudiu T. Supuran
The three-components one-pot Kabachnik-Fields reaction of sulfapyridine, diethyl phosphite, and aldehyde under thermal catalysis reaction condition in the presence of bismuth (III) triflate as a catalyst afford the corresponding sulfonamide-phosphonates (3a−3p) in good to excellent yields (78%−91%). The structures of the new synthesized compounds were elucidated and confirmed by variable spectroscopic
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Discovery of N-(phenylsulfonyl)thiazole-2-carboxamides as potent α-glucosidase inhibitors Drug Dev. Res. (IF 3.8) Pub Date : 2023-11-20 Jun Liu, Jia-Hao Li, Si-Yu Zhao, Yi-Qun Chang, Qiu-Xian Chen, Wen-Fu Wu, Shu-Meng Jiao, Haichuan Xiao, Qiang Zhang, Jian-Fu Zhao, Jun Xu, Ping-Hua Sun
In a search for novel nonsugar α-glucosidase inhibitors for diabetes treatment, a series of N-(phenylsulfonyl)thiazole-2-carboxamide derivatives were designed and synthesized, the α-glucosidase inhibitory activities were then evaluated. Several compounds with promising α-glucosidase inhibitory effects were identified. Among these, compound W24 which shows low cytotoxicity and good α-glucosidase inhibitory
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Anti-allodynic and anti-hyperalgesic activity of (±)-licarin A in neuropathic rats via NO-cyclic-GMP-ATP-sensitive K+ channel pathway Drug Dev. Res. (IF 3.8) Pub Date : 2023-11-20 Liliana Hernández-Vázquez, Brian Colín-Martínez, María Guadalupe Lara-Ruíz, Beatriz Cordova-Alonso, Estefanía González-Morales, Beatriz Godínez-Chaparro
The study aimed to examine the effect of intraperitoneal and intrathecal (±)-licarin A in neuropathic pain induced by L5 and L6 spinal nerve ligation (SNL) in male Wistar rats and the possible involvement of the NO-cGMP-ATP-sensitive K+ channel pathway. Neuropathic pain signs (allodynia and hyperalgesia) were evaluated on postoperative Day 14 using von Frey filaments. Single intraperitoneal (0.01,
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Design, synthesis of novel chromene-based scaffolds targeting hepatocellular carcinoma: Cell cycle arrest, cytotoxic effect against resistant cancer cells, apoptosis induction, and c-Src inhibition Drug Dev. Res. (IF 3.8) Pub Date : 2023-11-16 Eman K. A. Abdelall, Heba A. H. Elshemy, Madlen B. Labib, Fatma E. A. Mohamed
New chromene derivatives were synthesized based on 4-(3,4-dimethoxy)-4H-chromene scaffold. All target compounds exhibited cytotoxic activity against HepG2 cells (IC50 = 2.40–141.22 μM). Chromens 5 and 9 showed superior cytotoxicity over staurosporine (IC50 = 18.27 μM) and vinblastine (IC50 = 5.20 μM). c-Src kinase inhibition assay of compounds 5 and 9 displayed the dominant c-Src inhibitory activity
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Investigation of the activity of a novel tropolone in osteosarcoma Drug Dev. Res. (IF 3.8) Pub Date : 2023-11-14 Staci L. Haney, Dan Feng, Sai Sundeep Kollala, Yashpal S. Chhonker, Michelle L. Varney, Jacob T. Williams, James B. Ford, Daryl J. Murry, Sarah A. Holstein
Osteosarcoma (OS) is a primary malignant bone tumor characterized by frequent metastasis, rapid disease progression, and a high rate of mortality. Treatment options for OS have remained largely unchanged for decades, consisting primarily of cytotoxic chemotherapy and surgery, thus necessitating the urgent need for novel therapies. Tropolones are naturally occurring seven-membered non-benzenoid aromatic
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Heat-shock protein A12A attenuates oxygen-glucose deprivation/reoxygenation-induced human brain microvascular endothelial cell dysfunction via PGC-1α/SIRT3 pathway Drug Dev. Res. (IF 3.8) Pub Date : 2023-11-09 Jun Li, Shouyin Shen, Haiyan Shen
Ischemic stroke is a life-threatening brain disease with the leading cause of disability and mortality worldwide. Heat-shock protein A12A (HSPA12A) is recognized as a neuroprotective target for treating ischemic stroke; however, its regulatory mechanism has been not fully elucidated yet. Human brain microvascular endothelial cells (hBMECs) were induced by oxygen-glucose deprivation/reoxygenation (OGD/R)
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Function of proprotein convertase subtilisin/kexin type 9 and its role in central nervous system diseases: An update on clinical evidence Drug Dev. Res. (IF 3.8) Pub Date : 2023-11-09 Xiao-Bin Zhu, Yao-Yao Xu, Liu-Cheng Li, Jia-Bin Sun, Yu-Zhen Wang, Jie Chen, Chen Wang, Su Zhang, Liang-Yan Jin
Proprotein convertase subtilisin/kexin type 9 (PCSK9) has attracted lots of attention in preventing the clearance of plasma low-density lipoprotein cholesterol (LDL-C). PCSK9 inhibitors are developed to primarily reduce the cardiovascular risk by lowering LDL-C level. Recently, a number of pleiotropic extrahepatic functions of PCSK9 beyond the regulation of cholesterol metabolism, particularly its
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Medicinal polypharmacology: Exploration and exploitation of the polypharmacolome in modern drug development Drug Dev. Res. (IF 3.8) Pub Date : 2023-11-03 Sven Marcel Stefan, Muhammad Rafehi
At the core of complex and multifactorial human diseases, such as cancer, metabolic syndrome, or neurodegeneration, are multiple players that cross-talk in robust biological networks which are intrinsically resilient to alterations. These multifactorial diseases are characterized by sophisticated feedback mechanisms which manifest cellular imbalance and resistance to drug therapy. By adhering to the
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Nitroimidazole derivatives potentiated against tumor hypoxia: Design, synthesis, antitumor activity, molecular docking study, and QSAR study Drug Dev. Res. (IF 3.8) Pub Date : 2023-11-01 Aya M. Almatary, Walaa M. El Husseiny, Khalid B. Selim, Hassan M. H. Eisa
A hypoxic environment occurs predominantly in tumors. During the growth phase of a tumor, it grows until it exceeds its blood supply, leaving regions of the tumor in which the oxygen pressure is dramatically low. They are virtually absent in normal tissues, thus creating perfect conditions for selective bioreductive therapy of tumors. To this aim, a novel series of cytotoxic radiosensitizer agents
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Design, synthesis, and in-silico study of novel triarylethylene analogs with dual anti-estrogenic and serotonergic activity Drug Dev. Res. (IF 3.8) Pub Date : 2023-10-25 Tammy Mostafa, Miriam Albeir, Jannette Wober, Ashraf Abadi, Ismail Salama, Nermin S. Ahmed
Estrogen receptor is an important target in breast cancer. Serotonin receptors (5-HT2A and 5-HT2C, in particular) were investigated for a potential role in development and progression of breast cancer. Ligands that interact with estrogenic receptors influence the emotional state of females. Thus, designing selective estrogen receptor modulator (SERM) analogs with potential serotonergic activity is
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AS602801 treatment suppresses breast cancer metastasis to the brain by interfering with gap-junction communication by regulating Cx43 expression Drug Dev. Res. (IF 3.8) Pub Date : 2023-10-19 Zhigang Yang, Liguo Yang, Jun Zhang, Chenzeyue Qian, Yi Zhao
AS602801 has been reported as a potential drug candidate against brain metastasis by suppressing the gap-junction communication between lung cancer stem cells and astrocytes. In this study, we aimed to study the molecular mechanism underlying the role of AS602801 in the treatment of brain metastasis in breast cancer. We utilized female athymic BALB/c nude mice and MDA-MB-231/BT-474BR cells to establish
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Indole-based aryl sulfides target the cell wall of Staphylococcus aureus without detectable resistance Drug Dev. Res. (IF 3.8) Pub Date : 2023-10-15 Aditya G. Lavekar, Ritesh Thakare, Saima, Danish Equbal, Sidharth Chopra, Arun K. Sinha
Sulfur-containing classes of the scaffold “Arylthioindoles” have been evaluated for antibacterial activity; they demonstrated excellent potency against methicillin-resistant Staphylococcus aureus (MRSA) as well as against vancomycin-resistant strains and a panel of clinical isolates of resistant strains. In this study, we have elucidated the mechanism of action of lead compounds, wherein they target
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A growth-based assay using fluorescent protein emission to screen for S-adenosylmethionine synthetase inhibitors Drug Dev. Res. (IF 3.8) Pub Date : 2023-10-11 Ronald E. Viola, Gwenn G. Parungao, Robert M. Blumenthal
The use of cell growth-based assays to identify inhibitory compounds is straightforward and inexpensive, but is also inherently insensitive and somewhat nonspecific. To overcome these limitations and develop a sensitive, specific cell-based assay, two different approaches were combined. To address the sensitivity limitation, different fluorescent proteins have been introduced into a bacterial expression
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Artificial intelligence utility for drug development: ChatGPT and beyond Drug Dev. Res. (IF 3.8) Pub Date : 2023-10-10 David Gurwitz, Noam Shomron
1 INTRODUCTION Generative pretrained transformer (GPT) tools, most notably ChatGPT, are making headlines as the next revolution in artificial intelligence (AI). It affects diverse research fields, from biology and medicine to exact sciences, economics, engineering, and other knowledge-based and technology-driven fields. Novel AI applications, along with challenges, are foreseen in the fields of biomedical
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(E)-SIS3 suppressed osteosarcoma progression via promoting cell apoptosis, arresting cell cycle, and regulating the tumor immune microenvironment Drug Dev. Res. (IF 3.8) Pub Date : 2023-10-02 Zhen Huang, Chunlin Zhang, Kunpeng Zhu, Jianping Hu, Enjie Xu, Xiaolong Ma, Yongjie Wang, Yurun Zhu, Jiazhuang Zhu
Osteosarcoma is a prevalent malignant bone tumor with a poor prognosis. Mothers against decapentaplegic homolog 3 (Smad3) present as a therapeutic target in antitumor treatment, whereas its functions in the osteosarcoma have not been well explored. In the current study, we aimed to investigate the effects of Smad3 in the progression of osteosarcoma. The tumor immune single-cell hub 2 website was used
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Fluoxetine enhances the antitumor effect of olfactory ensheathing cell-thymidine kinase/ganciclovir gene therapy in human glioblastoma multiforme cells through upregulation of Connexin43 levels Drug Dev. Res. (IF 3.8) Pub Date : 2023-09-28 Saereh Hosseindoost, Ahmad R. Dehpour, Samaneh Dehghan, Seyed A. H. Javadi, Babak Arjmand, Ali Fallah, Mahmoudreza Hadjighassem
Glioblastoma multiforme (GBM) is the most invasive form of primary brain astrocytoma, resulting in poor clinical outcomes. Herpes simplex virus thymidine kinase/ganciclovir (HSV-TK/GCV) gene therapy is considered a promising strategy for GBM treatment. Since Connexin43 (Cx43) expression is reduced in GBM cells, increasing Cx43 levels could enhance the effectiveness of gene therapy. The present study
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A new triazolyl-indolo-quinoxaline induces apoptosis in gastric cancer cells by abrogating the STAT3/5 pathway through upregulation of PTPεC Drug Dev. Res. (IF 3.8) Pub Date : 2023-09-27 Rajaghatta N. Suresh, Young Y. Jung, Chakrabhavi D. Mohan, Shalini V. Gowda, Kachigere B. Harsha, Kempegowda Mantelingu, Gautam Sethi, Kwang S. Ahn, Kanchugarakoppal S. Rangappa
Signal transducer and activator of transcription 3 (STAT3) and STAT5 are the transcription factors that have been studied extensively in relevance to the development of cancers in humans. Suppression of either STAT3 or STAT5-mediated signaling events has been demonstrated to be effective in inducing cytotoxicity in cancer cells. Herein, new hybrids of triazolyl-indolo-quinoxaline are synthesized and
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Pyridazine derivatives as selective COX-2 inhibitors: A review on recent updates Drug Dev. Res. (IF 3.8) Pub Date : 2023-09-26 Sara Y. Ewieda, Eman M. Ahmed, Rasha A. Hassan, Marwa S. A. Hassan
Selective cyclooxygenase (COX)-2 inhibitors have several advantages over nonselective COX inhibitors (nonsteroidal anti-inflammatory drugs [NSAIDs]), including the absence of adverse effects (renal and hepatic disorders) associated with the long-term use of standard NSAIDs, as well as an improved gastrointestinal profile. The pyridazine nucleus is regarded as a promising scaffold for the development
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Discovery of novel pyrido[3,2-d]pyrimidine derivatives as selective and potent PI3Kδ inhibitors Drug Dev. Res. (IF 3.8) Pub Date : 2023-09-21 Huanrong Bai, Jiajia Sun, Hao Lei, San-Qi Zhang, Bo Yuan, Mengyan Ma, Minhang Xin
The δ isoform of class I PI3K (PI3Kδ) has been shown as a promising target for the treatment of hematologic malignancies and immune diseases. Herein, a series of pyrido[3,2-d]pyrimidine derivatives were designed, synthesized and evaluated for the preliminary bioactivity. Compared with idelalisib, compound S5 exhibited excellent enzyme activity against PI3Kδ (IC50 = 2.82 nM) and strong antiproliferation
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Cover Image, Volume 84, Issue 6 Drug Dev. Res. (IF 3.8) Pub Date : 2023-09-11 Lindsay H. Burns, Zhe Pei, Hoau-Yan Wang
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Artificial intelligence revolutionizing drug development: Exploring opportunities and challenges Drug Dev. Res. (IF 3.8) Pub Date : 2023-09-15 Prafulla C. Tiwari, Rishi Pal, Manju J. Chaudhary, Rajendra Nath
By harnessing artificial intelligence (AI) algorithms and machine learning techniques, the entire drug discovery process stands to undergo a profound transformation, offering a myriad of advantages. Foremost among these is the ability of AI to conduct swift and efficient screenings of expansive compound libraries, significantly augmenting the identification of potential drug candidates. Moreover, AI
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Carbamate as a potential anti-Alzheimer's pharmacophore: A review Drug Dev. Res. (IF 3.8) Pub Date : 2023-09-11 Yash Pal Singh, Navneet Kumar, Brijesh Singh Chauhan, Prabha Garg
Alzheimer's disease (AD) is a progressive age-related neurodegenerative brain disorder, which leads to loss of memory and other cognitive dysfunction. The underlying mechanisms of AD pathogenesis are very complex and still not fully explored. Cholinergic neuronal loss, accumulation of amyloid plaque, metal ions dyshomeostasis, tau hyperphosphorylation, oxidative stress, neuroinflammation, and mitochondrial
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Virucidal activity of trehalose 6-monolaurate against dengue virus in vitro Drug Dev. Res. (IF 3.8) Pub Date : 2023-09-09 Jeng-Wei Lu, Chin-Kai Huang, Yen-Chen Chen, Guan-Chiun Lee, Yi-Jung Ho
Dengue fever is an acute febrile disease caused by dengue virus (DENV) infection. Over the past 60 years, DENV has spread throughout tropical regions and currently affects more than 50% of the world's population; however, there are as of yet no effective anti-DENV drugs for clinical treatment. A number of research teams have investigated derivatives of glycolipids as possible agents for the inhibition
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Tryptamine: A privileged scaffold for the management of Alzheimer's disease Drug Dev. Res. (IF 3.8) Pub Date : 2023-09-07 Yash P. Singh, Harish Kumar
Alzheimer's disease (AD) is a chronic and irreversible neurodegenerative disease associated with aging. It is characterized by the progressive loss of memory and other cognitive functions. Although the exact etiology of AD is not well explored, several factors, such as the deposition of amyloid-β (Aβ) plaques, hyperphosphorylation of tau protein, presence of low levels of acetylcholine, and generation
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Design, synthesis, and antitumor screening of new thiazole, thiazolopyrimidine, and thiazolotriazine derivatives as potent inhibitors of VEGFR-2 Drug Dev. Res. (IF 3.8) Pub Date : 2023-09-03 Alaa A. Abd Elhameed, Ahmed R. Ali, Hazem A. Ghabbour, Said M. Bayomi, Nadia S. El-Gohary
New thiazole, thiazolopyrimidine, and thiazolotriazine derivatives 3–12 and 14a–f were synthesized. The newly synthesized analogs were tested for in vitro antitumor activity against HepG2, HCT-116, MCF-7, HeP-2, and Hela cancer cells. Results indicated that compound 5 displayed the highest potency toward the tested cancer cells. Compound 11b possessed enhanced effectiveness over MCF-7, HepG2, HCT-116