In an effort to develop potent anti-influenza drugs that inhibit the activity of influenza virus RNA-dependent RNA polymerase (IAV RdRp), a database of nucleoside triphosphates with ~800 molecules were docked with the homology model of IAV RdRp from A/PR/8/34/H1N1 strain. Out of top 12 molecules that bind with higher affinities to the catalytic site of IAV RdRp above and below the PB1 priming loop

Nigella glandulifera Freyn et Sint (N. glandulifera) is frequently added to naan (a kind of crusty pancake and a favorite food of the Uyghur and Kazak people) as a spice. The water decoction of N. glandulifera was used as traditional Uighur medicine to treat tinnitus, amnesia, amenorrhea, hypogalactia, heat stranguria, urethral calculus, alopecia and hair-blacking, edema, and bronchial asthma. This

The 7-azaindole scaffold attracts attention due to its value in the design of inhibitors of diseases related protein kinases. However, this scaffold has not been evaluated against Haploid germ cell-specific nuclear protein kinase (Haspin). Herein, we report the synthesis of a select set of 7-azaindole derivatives and their evaluation against Haspin. The compounds were also evaluated against CDK9/Cyclin

Inflammation is an important, normal, and complex host defense response to injury, autoimmune responses or infectious agents. However, chronic inflammation is associated with diseases like rheumatoid arthritis, cancers, cardiovascular diseases, diabetes, and obesity, and over 60% of deaths worldwide. Interleukine-6 is one of the key proinflammatory cytokines involved in inflammation processes and therefore

A hybrid pharmacophore approach was applied to design and synthesize a series of benzo[b]thiophene-diaryl urea derivatives 17a–g with potential anticancer effect. In vitro antiproliferative activities of all target compounds were evaluated against HT-29 and A549 cancer cell lines. Three compounds 17b, 17d, and 17f exhibited antiproliferative activities on both cell lines comparable to that of the positive

The diaryl ureas are very important fragments in medicinal chemistry. By means of computer-aided design, 1-aryl-3-[4-(pyridin-2-ylmethoxy)phenyl]urea derivatives were designed and synthesized, and evaluated for their antiproliferative activity against A549, HCT-116, PC-3 cancer cell lines, and HL7702 human normal liver cell lines in vitro by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium

This communication describes a variety of nucleophilic ring openings of N-arylated oxathiazinane heterocycles. We find that this reaction is compatible with phenoxides, naphthoxides, and thiolates and allows for the rapid assembly of N-aryl-amino ethers and N-aryl-amino thioethers. Fourteen examples are shown and a mechanistic pathway is hypothesized.

Eighteen novel N-2,4-dimethoxyphenyl dithiolopyrrolone derivatives inhibiting bacterial RNA polymerase (RNAP) were synthesized based on dithiolopyrrolone scaffold. Some compounds displayed potent antimicrobial activity against Gram-positive bacteria of Staphylococcus aureus and Streptococcus pneumoniae, but not the Gram-negative bacteria of Escherichia coli and Pseudomonas aeruginosa. Moreover, the

The role of mast cells can be protective or harmful; depending upon the physiological/pathological condition in which they get activated. The latter role is due to mast cell degranulation and release of an array of incendiary mediators. Mast cells have a well-established role in diseases like allergy, eczema, anaphylactic shock, mastocytosis, and other miscellaneous mast cell diseases. Previously,

Infectious diseases such as tuberculosis and leishmaniasis are leading causes of human death. One of the major factors contributing to the poor control of these diseases is primarily the reduced effectiveness of the existing chemotherapies as result of the increasing rise of multidrug-resistant strains of their causative agents. This leads to the imperative need to develop new and effective drugs.

This article reports the diastereoselective synthesis of some novel naphthalimido and bis-naphthalimido β-lactam derivatives and a preliminary evaluation of their anticancer properties. The reactions were completely diastereoselective, leading exclusively to the formation of cis-β-lactams 11a–l and trans-bis-β-lactams 16a–g. All of these compounds were obtained in good to excellent yields and their

Gibberellic acid (GA3) is a tetracyclic diterpene compound which displays interesting bioactivities. Recently, its potential use for preparing antitumor drug leads has been highlighted, and various modification methods of GA3 have been reported. Aiming at investigating GA3 derivatives with potential antitumor activities, ring distortion of GA3 under different conditions was carried out, and this was

In this study, we report the synthesis and biological evaluation of a variety of α- and β-hydroxy substituted amino acid derivatives as potential amino acid subunits in inhibitors of GABA uptake transporters (GATs). In order to ensure that the test compounds adopt a binding pose similar to that presumed for related larger GAT inhibitors, lipophilic residues were introduced either at the amino nitrogen

The skin is an important barrier against environmental factors. Foregoing studies has shown that human KLK7 is a protease which promoted epidermal shedding, affected the epidermal barrier and increased the risk of atopic dermatitis. In this study, the structure and activity relationship of 40 human KLK7 inhibitors was explored by three-dimensional quantitative structure–activity relationship (3D-QSAR)

Nowadays, the emergence of superbugs is one of the most serious public health problems. Strains of Staphylococcus aureus and Klebsiella pneumoniae, resistant to many antimicrobials available in clinical practice, have become increasingly common. The development of new drugs for the treatment of infections caused by these pathogens is necessary and urgent. A series of 11 analogs of marine 3-alkylpyridine

In targeted therapy of breast cancer, human epidermal growth factor receptor 2 HER2 (PDB ID: 3PP0) is being considered as a promising route to design novel anti-breast cancer drugs. In this work, we report two of novel N-substituted pyrrolidine at C-8 position of quinolone derivatives 18 and 19, their synthesis under microwave technique, spectral methods, molecular docking study and anti-HIV activities

P-glycoprotein (P-gp) induction and/or activation have been proposed as therapeutic strategies in intoxication scenarios, by reducing the intestinal absorption of xenobiotics, including drugs. Oxygenated xanthones (OXs) have been described as P-gp modulators and, therefore, the main goals of this study were to: (a) investigate the potential modulatory effect of six OXs on P-gp expression and activity

Lapachol (1) is a well-studied natural product isolated from plants of the Bignoniaceae family and demonstrates diverse biological effects. Historically, chemical transformation of the lapachol scaffold has yielded new derivatives with impressive biological activity and rich chemical diversity. β-lapachone (2), α-lapachone (3), and 2-acetylfuronaphthoquinone (4) are examples of analogs derived from

In this study, pillar[5]arene containing ten terminal alkynyl-functional group was prepared and carried out an optimization procedure for target molecule with using 5-hydroxyquinoline molecule known with biological activity. The novel molecule was named as iso-QP[5] and characterized by FT-IR, melting point, NMR, elemental analysis, and mass spectroscopy. The aim was to evaluate the anticancer effects

Background Alzheimer’s disease (AD) is characterized by cognitive impairment and loss of immediate memory resulting from neuronal death in different brain areas, mainly those producing acetylcholine. Acetylcholinesterase inhibitors improve cognitive function, delay mental deterioration, and reduce other symptoms. Despite being the cornerstone for treating mild–moderate AD, these compounds are only

A new series of 1-(4-methyl-2-aryl-1,3-thiazol-5-yl)-2-(4-aryl-1,2,3-triazol-1-yl)ethanol (6a-t) have been synthesized by a click reaction of 2-azido-1-(4-methyl-2-phenylthiazol-5-yl)ethanone (3a-e) with substituted ethynylbenzene (4a-c) followed by reduction with sodiumboro hydride. The newly synthesized 1-(4-methyl-2-aryl-1,3-thiazol-5-yl)-2-(4-aryl-1,2,3-triazol-1-yl)ethanol derivatives were screened

The successful use of PARP1 inhibitors like olaparib (Loparza®) in the treatment of BRCA1/2-deficient breast cancer has provided clinical proof-of-concept for applying personalized medicine based on synthetic lethality to the treatment of cancer. Unfortunately, all marketed PARP1 inhibitors act by competing with the cofactor NAD+ and resistance is already developing to this anticancer mechanism. Allosteric

Multitarget molecules are considered as an effective way for the treatment of AD, instead of the classic one-drug-one-target strategy because of the multifactorial nature of AD. A variety of studies indicate that several enzymes inhibitors can be useful in the treatment of AD, including acetylcholinesterase (AchE), butyrylcholinesterase (BuChE) and monoamine oxidase (MAO). Various substituted quinoxaline-hydrazone

Symmetrical α,αʹ-bis(arylidene)ketones were prepared by acid-catalyzed aldol condensations between aliphatic ketones (e.g., cyclopentanone, 4-alkylcyclohexanones, tetrahydropyran-4-one, and tetrahydrothiopyran-4-one) and two equivalents of an aromatic hydroxyaldehyde (e.g., 4-hydroxybenzaldehyde, 3,4-dihydroxybenzaldehyde, vanillin, isovanillin, and 3-fluoro-4-hydroxybenzaldehyde). Most of the compounds

In this paper, 21 naphthalene-chalcone derivatives were synthesized and their biological effects were evaluated. The results showed that compounds 2a–2u displayed clear antidepressant activity at 30 mg/kg in the forced swimming test. Compounds 2h, 2o, 2t, and 2u exhibited a good antidepressant effect in the forced swimming test and tail suspension test at 30 mg/kg. Compounds 2h, 2o, 2t, and 2u but

Selective cyclooxygenase-2 (COX-2) inhibitors have exhibited notable medicinal importance. In recent years, the discovery of new anti-inflammatory agents as selective COX-2 inhibitors has acquired more attention. This is due to the fact that currently available COX-2 inhibitors are linked with adverse effects. Various new organic scaffolds are being explored as new COX-2 inhibitors. In this review

Molecular hybridization has become a new promising way to treat multifactorial diseases with a single compound that acts on multiple targets. The combination of several functional pharmacophore groups in one molecule can lead to a stronger therapeutic effect due to the ability to bind to several targets and possible synergistic interactions. The concept of multifunctional agents is being actively developed

A series of sulphonyl acetamide analogues were generated on the quinazoline ring through a multistep reaction starting from 2-mercapto-3H-quinazolin-4-one. The library of synthesised analogues was screened for in vitro cytotoxic activity against various human cancer cell lines such as HCT-1 and HT-15 (colon), MCF-7(Breast), PC-3 (Prostrate), SF268 (CNS) using MTT method. From the bioassay results,

Neprilysin (NEP, EC: 3.4.24.11) is an enzymatic membrane protein considered the prototype of the M13 zinc metallopeptidase family. Inhibitors of this enzyme constitute therapeutic targets for cardiovascular diseases. In spite of the existing alternatives for the treatment of these pathologies, the quality of life and the prognosis of the patients remain precarious, so the discovery of new drugs is

The coupling of acetylated piperazinylamide spacered triterpenoic oleanolic acid and ursolic acid with meta or para substituted carboxylated malachite green analogs gave conjugates 10, 11, 15, and 16 that were cytotoxic for several human tumor cell lines. Especially, an oleanolic acid-derived compound 10 was cytotoxic for MCF-7 human breast carcinoma cells (EC50 = 0.7 μM). These derivatives represent

Based on our previous work, a series of indazolyl-substituted piperidin-4-yl-aminopyrimidines, which were firstly used as anti-HIV agents, were evaluated for their anticancer potency in five cancer cell lines. Notably, they exhibited excellent activities with IC50 values ranging from 2.29 to 22.89 μM in H1975 cells, among which 6c–e displayed lower cytotoxicity to normal lung cells than gefitinib.

Lung cancer is the primary reason of cancer death worldwide, with an annual incidence of ~1.3 million cases. Therefore, finding better and more effective methods to treat lung cancer has become very pressing. PDB-1 is a new C-27-carboxylated-lupane-triterpenoid derivative isolated from Potentilla discolor Bunge and is a type of compound that is rarely found in natural sources. This research investigated

Activation of the transcription factor Nrf2 via the Keap1-Nrf2-ARE signaling system regulates the transcription and subsequent expression of cellular cytoprotective proteins and plays a crucial role in preventing pathological conditions exacerbated by the overproduction of oxidative stress. In addition to electrophilic modulators, direct non-covalent inhibitors that interrupt the Keap1-Nrf2 protein-protein

A new series of phthalimide-benzamide-1,2,3-triazole hybrids 8a–k as α-glucosidase inhibitors was designed and synthesized. The biological evaluation of compounds 8a–k against yeast α-glucosidase demonstrated that all they have excellent inhibitory activity in comparison with standard inhibitor acarbose. Among them, the most potent compound was compound 8d with inhibitory activity 18.5-fold more than

A need exists to develop safe and efficacious medications to treat major diseases such as cancer and infectious diseases. In response to this need, we synthesized a novel enaminone, which structurally belongs to the trithiocarbonate class engrafted by an enaminone group. The anticancer and antimicrobial activities were evaluated by utilizing three different types of human cancer (MDA-MB-231, LoVo,

Patients with advanced-stage cervical cancer have a high rate of morbidity and mortality, predominantly due to the metastasis of cervical cancer cells. Therefore, the development of novel agents to prevent metastasis is required for improved cervical cancer therapeutics. SNX-2112, a potent and selective Hsp90 inhibitor, is an anticancer candidate in clinical trials for the treatment of some solid tumors

This research reported the design and synthesis of some influential new pyrrolone derivatives bearing a pyrazole scaffold with the evaluation of their antiviral activity against Newcastle disease virus (NDV) in specific pathogen free (SPF) chicken embryos and immune boosting properties of these substances in SPF chicks. The building block synthon was the pyrazolyl acid hydrazide, derived from 2(3H)-furanone

New hexahydro-2H-chromenes were synthesized by reactions of monoterpenoid (1R,2R,6S)-3-methyl-6-(prop-1-en-2-yl)cyclohex-3-ene-1,2-diol with aliphatic ketones in the presence of montmorillonite clay H+-K10. The compounds formed and isolated as a pair of diastereoisomers were evaluated for their analgesic activity in vivo. It was found that the analgesic activity of (4aR,8R,8aR)-4,7-dimethyl-3,4,4a

A new series of tetrahydroquinoline-isoxazoline hybrid derivatives (3a–p) were efficiently synthesized involving 1,3-dipolar cycloaddition reaction according to click chemistry approach, from the corresponding N-allyl-4-(2-oxopyrrolinidyl-1)-tetrahydroquinolines preformed, with moderate to good yields (63–77%). To establish new candidates with anticancer activity, the antiproliferative effect of these

Maytenus is a genus in the plant family Celastraceae, the species of which are primarily distributed in China, Brazil, Uruguay, Paraguay, and northern Argentina. These plants have long been used as a resource for the development of medicines. The latest advances in the pharmacology and phytochemistry of Maytenus are reviewed in this paper. Studies have discovered that Maytenus spieces have efficacy

Chronic inflammation mediated by several markers promotes cancer progression. Leukotriene A4 hydrolase (LTA4H), an inflammatory marker, is highly expressed in colorectal cancer. Therefore, inhibition of LTA4H could reduce the incidence and progression of this cancer type. Several studies supported the valuable effects of naturally occurring diterpenes against several diseases. In this study, a new

Chemical investigation of pharmacologically active compounds from the Echinoidea sea urchin Stomopneustes variolaris resulted in the separation of an unreported cembrane type of diterpenoid, which was characterised as 4-hydroxy-1-(16-methoxyprop-16-en-15-yl)-8-methyl-21,22-dioxatricyclo[11.3.1.15,8]octadecane-3,19-dione by spectroscopic experiments. The compound exhibited greater inhibitory potential

Traditional edible natural products enclose a wealth of anticoagulants that can be prospected for new selective factor Xa inhibitors. Unlike multitargeted anticoagulants, selective factor Xa inhibitors effectively block coagulation cascade with a broader therapeutic window. In the present study, an in-house database comprises 3D structures of 1571 compounds from 26 natural products previously reported

Abstract The aim of the research was to study the wide range of anticonvulsant effects of new 3- and 4-benzoylpyridines oxime derivatives in comparison with the reference drug valproic acid, it included assessment of motor and EEG convulsive state manifestations and epileptic status. To identify the most effective compound we studied the anticonvulsant effects in the models of generalized convulsions

Abstract A simple and environment friendly one-pot synthesis of ethyl 3,5-dicyano-6-oxo-2,4-diarylpiperidine-3-carboxylate derivatives from aryl aldehydes, ethyl cyanoacetate, and ammonium acetate was developed in aqueous medium without using a catalyst. The significant features of this method are easy, inexpensive experimental procedures with short reaction time and high yield. The use of water as

Abstract Bruton’s tyrosine kinase (BTK) is critical for B-cell receptor signaling and related to many types of human cancers. However, the drug resistance and off-target effect of present traditional BTK inhibitors occurred over time. As a new strategy for drug development, the proteolysis targeting chimera (PROTAC) has been proved to target varieties of proteins. Here SPB5208 (4-(2-(2-(2-(2-(3-(4-amino-3-(4-phenoxy

Abstract Kinase inhibitor selectivity is a major concern for the design of small-molecule compounds. As a member of serine/threonine protein kinase family, glycogen synthase kinase 3β (GSK3β) is involved in diverse biological processes and abnormal dysregulation of its activity has been associated with several pathologies, including type II diabetes, Alzheimer’s disease, bipolar disorders, and cancers

Abstract The present study aimed at the development of fluorescent inhibitors addressing the GABA transporters mGAT1–mGAT4 as potential tool compounds in fluorescence based biological assays. The design of these fluorescent GAT inhibitors followed the structural motifs common for many GAT1–GAT4 inhibitors publicly known except that the lipophilic domain present in this compounds was replaced by a BODIPY

Abstract The orphan nuclear receptors estrogen-related receptors (ERRs) bind to the estrogen-related receptor response element (ERRE) to regulate transcriptional programs in cellular metabolism and cancer cell growth. In this study, we evaluated the potential for a pyrrole-imidazole polyamide to block ERRα binding to ERREs to inhibit gene expression. We demonstrated that the ERRE-targeted polyamide

Abstract Valosine containing protein (VCP/p97), which involves in several important cellular functions and plays an important role in ubiquitin-mediated misfolding protein degradation, has been found to be a novel target for the treatment of a range of cancers, such as lung cancer and breast cancer. In this study, the atom-based three-dimensional quantitative structure–activity relationship (3D-QSAR)

Abstract Acteoside (ACT) is one of the most major components isolated from Cistanches Herba, a traditional Chinese medicine. However, its extensive pharmacological effects and multitarget features cause lacking of a systematic overview of its molecular mechanisms. In this study, we aimed to predict the potential targets and pharmacological mechanisms of ACT via network pharmacology strategy and provide

Abstract In the search for new therapeutic alternatives for Chagas disease, a series of six aryloxy -naphthoquinone derivatives were synthesized and evaluated in vitro against Trypanosoma cruzi epimastigotes of the Tulahuén 2, INC-5, and NINOA strains. The compounds 3d and 4a showed better or similar trypanosomicidal activity than the reference drug nifurtimox. In addition, 3d and 4a also elicited

Abstract A series of novel thiosemicarbazone analogs (4a–t, 6a–j) were synthesized and evaluated for their cytotoxic activities. The obtained results showed that thiochromanone-based thiosemicarbazones substituted primarily at the C-8 position exhibited higher cytotoxicity than the corresponding 1,1-dioxo-thiochromanone-, benzothiazepine-, and 1,1-dioxo-benzothiazepine-based analogs. Significantly

Abstract In this study, the main aim was synthesis of dimeric compounds, which contain lithocholic acid and a triazole structure to investigate the selective cellular and molecular antiproliferative and proapoptotic potential of these products in healthy embryonic fibroblast (MEF), cervix cancer (HeLa), and breast cancer (MCF-7) cells. Four ester (5a–d) and five dimeric (6a–d, 7) out of nine novel

Abstract A series of new 3-(5-methyl-1-aryl-1H-1,2,3-triazol-4-yl)-1-phenyl-1H-pyrazole-4-carbaldehydes 4(a–g) and their benzimidazole derivatives 6(a–g) were synthesized under both conventional and microwave irradiation methods. However, we successfully achieved good yields in shorter reaction times under microwave irradiation. All the synthesized scaffolds were characterized by 1H NMR, 13C NMR, IR

Abstract A series of 2-amino-4-aryl-5-oxo-4,5-dihydropyrano[3,2-c]chromene-3-carbonitrile (4a–m) were synthesized via a one-pot three component condensation reaction between 4-hydroxy-2H-chromen-2-one, various aryl aldehydes and malononitrile in the presence of piperidine as a catalyst in ethanol under microwave irradiation conditions, with good to excellent yields. The structure elucidations of all

We have discovered a new class of pyrido[b]bindole derivatives that show potent and broad spectrum anticancer activity with IC50 values down to submicromolar levels. Structure-activity relationship data acquired with the compounds as antiproliferative agents against several cancer cell lines, i.e. human HCT116 colon cancer cell line, and HPAC, Mia-PaCa2 and Panc-1 pancreatic cancer cell lines, were

A series of isoxazole and triazole derivatives, with interesting bioactive scaffolds, were examined for their in vitro antibacterial, antifungal, and antiprotozoal activities. These compounds exhibited antitrypanosomal activity comparable to difluoromethylornithine (DMFO), a drug used in the treatment of human African trypanosomiasis. Isoxazole analogues 1, 3 and 4, and triazole derivatives 16, 17

Piliostigma thonningii (Schumach.) Milne-Redhead. (Leguminosae) is used for various medicinal purposes in African countries. Phytochemical investigation of P. thonningii yielded two compounds newly isolated from natural sources, 2β-methoxyclovan-9α-ol (1), and methyl-ent-3β-hydroxylabd-8(17)-en-15-oate (2), along with 14 known compounds (3-16). Compounds 1 and 4 (alepterolic acid) showed potential

A set of psychoactive drugs has been analyzed with the use of quantitative structure-activity/property relationships methods. The purpose of this study was to demonstrate both the common and differentiating characteristics of the above-mentioned chemical compounds, physicochemical as well as pharmacological based on the quantum chemical calculations and selected biological activity data and chromatographic