Hepatitis B Virus (HBV) remains a critical global health issue, with substantial morbidity and mortality. Current therapies, including interferons and nucleoside analogs, often fail to achieve complete cure or functional eradication. This review explores recent advances in anti-HBV agents, focusing on their innovative mechanisms of action. HBV entry inhibitors target the sodium taurocholate cotransporting

Protein Arginine Methyltransferase 6 (PRMT6) is a Type I PRMT enzyme that plays a role in the epigenetic regulation of gene expression by methylating histone and non-histone proteins. It is also involved in various cellular processes, including alternative splicing, DNA repair, and cell signaling. Furthermore, PRMT6 exerts multiple effects on cellular processes such as growth, migration, invasion,

As a defense mechanism against deleterious stimuli, inflammation plays a vital role in the development of many disorders, including atherosclerosis, inflammatory bowel disease, experimental autoimmune encephalomyelitis, septic and non-septic shock, and non-alcoholic fatty liver disease (NAFLD). Despite the serious adverse effects of extended usage, traditional anti-inflammatory medications, such as

Indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) play a pivotal role in regulating kynurenine catabolism pathway and immunosuppressive environment, which are promising drug targets for cancer immunotherapy. In this work, a variety of isoquinoline derivatives were designed, synthesized and evaluated for the inhibitory activity against IDO1 and TDO. The enzymatic assay and structure-activity

Methicillin-resistant (MRSA) has emerged as a major pathogen causing infections in hospitals and the community, and there is an urgent need for the development of novel antibacterials to combat MRSA infections. Herein, a series of amphiphilic honokiol derivatives containing an oxazolethione moiety were prepared and evaluated for their antibacterial and hemolytic activities. The screened optimal derivative

Ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) is the dominant hydrolase of 2′,3′-cyclic GMP-AMP (cGAMP). Inhibition of ENPP1 contributes to increased cGAMP concentration and stimulator of interferon gene (STING) activation, with the potential to boost immune response against cancer. ENPP1 is a promising therapeutic target in tumor immunotherapy. To date, orally bioavailable ENPP1 inhibitors

A growing body of evidence points to the existence of a crosstalk between the endovanilloid (EV)- and the endocannabinoid (EC) systems, leading to the concept of a single system based on a shared set of endogenous ligands and regulation mechanisms. The EV/EC system encompasses the ion channel TRPV1, the G protein coupled receptors CB1 and CB2, their endogenous ligands and the enzymes for biosynthesis

Pulmonary arterial hypertension (PAH) is a severe pulmonary vascular disorder marked by vascular remodeling, which is linked to the malignant phenotypes of pulmonary vascular cells. The prevailing therapeutic approaches for PAH tend to neglect the potential role of vascular remodeling, leading to the clinical prognosis remains poor. Previously, we first demonstrated that heat shock protein (Hsp110)

In recent years, the number of cancers has soared, becoming one of the leading causes of human death. At the same time, marine anticancer substances have been the focus of marine drug research. Marine alkaloids derived from marine invertebrates like sponges are an important class of secondary metabolites, which have good bioactivities of blocking the cancer cell cycle, inducing autophagy and apoptosis

Photoswitchable molecules exhibit light-dependent biological activity which allow us to control the therapeutic effect of drugs with high precision. Such molecules could solve some of the limitations of anticancer drugs by providing a localised effect in the tumour. Histone deacetylase inhibitors (HDACis) constitute a promising drug class for oncology whose application is often limited by a lack of

Synergetic inhibition of FMS-like tyrosine kinase 3 (FLT3) and histone deacetylase (HDAC) by small molecule chimera presents a promising therapeutic approach for acute myeloid leukemia (AML) with FLT3 mutations. In this study, we first observed that the combined use of FLT3 inhibitor gilteritinib and HDAC inhibitor vorinostat increased the survival rate of leukemia xenograft mouse model. Then, we employed

Idiopathic pulmonary fibrosis (IPF) is a progressive respiratory disease with no known cause. It is characterized by widespread inflammation and structural abnormalities in the alveoli of the lungs, ultimately leading to the development of pulmonary fibrosis. Triptolide (TP), an epoxy-diterpene lactone compound known for its potent anti-inflammatory and antifibrotic effects, was limited clinical use

Boronated carbohydrate derivatives have good potential for targeting malignant cells in Boron Neutron Capture Therapy (BNCT) due to their preferential glucose uptake. In particular, with the introduction of the ammonium trifluoroborate moiety, boronated sugars can function as both BNCT agents and Positron Emission Tomography (PET) tracers. Their F radiolabeling allows real-time tracking of biodistribution

Drug candidates with poor solubility have been recognized as the cause of many drug development failures, owing to the fact that low solubility is unfavorable for physicochemical, pharmacokinetic (PK) and pharmacodynamic (PD) properties. Given the imperative role of solubility during drug development, we herein summarize various strategies for solubility optimizations from a medicinal chemistry perspective

This article profiles 13 newly approved nitrogen-containing heterocyclic drugs by the U.S. Food and Drug Administration (FDA) in 2023. These drugs target a variety of therapeutic areas including proteinuria in patients with IgA nephropathy, migraine in adults, Rett syndrome, PI3Kδ syndrome, vasomotor symptoms, alopecia areata, acute myeloid leukemia, postpartum depression, myelofibrosis, and various

Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) is a promising target for the diagnosis and treatment of various diseases, especially neurodegenerative disorders. Developing PET imaging probes targeting RIPK1 is beneficial for visualizing the connections between RIPK1 and diseases, as well as for related drug development. In this study, we report the design and synthesis of a series

Boron neutron capture therapy (BNCT) is a highly targeted, selective and effective technique to cure various types of cancers, with less harm to the healthy cells. In principle, BNCT treatment needs to distribute the boron (B) atoms inside the tumor tissues, selectively and homogeneously, as well as to initiate a nuclear fission reaction by capturing sufficient neutrons which releases high linear energy

This review comprehensively summarizes recent advances in the field of hydrazinecarboxamide (semicarbazide) derivatives, highlighting their significant therapeutic potential and a broad spectrum of biological activities. As a promising and privileged scaffold in medicinal chemistry, hydrazinecarboxamides have emerged as a versatile class of compounds with significant bioactive properties. Based on

Nitrobenzothiazinones (BTZs) are undergoing late-stage development as a novel class of potent antitubercular drug candidates with two compounds in clinical phases. BTZs inhibit decaprenylphosphoryl-β--ribose oxidase 1 (DprE1), a key enzyme in cell wall biosynthesis of mycobacteria. Their mechanism of action involves an -reduction of the nitro moiety to a reactive nitroso intermediate capable of covalent

Various therapeutic targets and approaches are commonly employed in the management of Type 2 Diabetes. These encompass diverse groups of drugs that target different mechanisms involved in glucose regulation. Inhibition of the DPP-4 enzyme has been proven an excellent target for antidiabetic drug design. Our previous work on discovering multitarget antidiabetic drugs led to the identification of a gallic

Cancer is a major societal, public health, and economic burden in the 21st century, with 9.7 million deaths in 2022 (9.96 million in 2020) and 20 million new cancer cases (19.6 million in 2020). Considering the increasing number of cancer cases and deaths, heterocyclic compounds always paved the gold mine for the development of potential anticancer drugs as these compounds have unique flexibility and

is a genus of marine bacteria and a promising source of natural products with antibacterial, antifungal, and antifouling bioactivities To accelerate the exploration of new compounds from this genus, we applied the gene-first approach to study 632 public genomes. We identified 3968 biosynthetic gene clusters (BGCs) involved in the biosynthesis of secondary metabolites and classified them into 995 gene

In this work, a series of nineteen novel pyrano[2,3-c]pyrazole-4-aminoquinoline hybrids were synthesized as potent antimalarial agents by covalently linking the scaffolds of 4-aminoquinoline and pyrano[2,3-c]pyrazoles an ethyl linker and characterized using Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance spectroscopy (NMR). Molecular docking was used to test each hybrid's

G-quadruplexes (G4s) are non-canonical nucleic acids secondary structures that involve in the regulation of some key biological processes, such as replication, transcription, and translation. G4s have been extensively described in the genomes of human and related diseases. In recent years, G4s were identified in several livestock viruses, including those of the emerging epidemics, like Nipah virus

Death-associated protein kinase 1 (DAPK1) is a phosphotransferase in the serine/threonine kinase family. Inhibiting DAPK1 is expected to be beneficial in treating Alzheimer's disease and protecting neuronal cells during cerebral ischemia. In this study, we demonstrated that the natural chalcone isoliquiritigenin inhibits DAPK1 in an ATP-competitive manner, and we synthesized halogen derivatives to

The growing prevalence of MDR and XDR bacterial pathogens is posing a critical threat to global health. Traditional antibiotic development paths have encountered significant challenges and are drying up thus necessitating innovative approaches. Drug repurposing, which involves identifying new therapeutic applications for existing drugs, offers a promising alternative to combat resistant pathogens.

Alzheimer's disease (AD) is the most common form of dementia among the elderly, accounting for 60 %–70 % of cases. At present, the pathogenesis of this condition remains unclear, but the hydrolysis of acetylcholine (ACh) is thought to play a role. Acetylcholinesterase (AChE) can break down ACh transmission from the presynaptic membrane and stop neurotransmitters' excitatory effect on the postsynaptic

A large scale of pandemic coronavirus disease (COVID-19) in the past five years motivates a great deal of endeavors donating to the exploration on therapeutic drugs against COVID-19 as well as other diseases caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Herein is an overview on the organic small molecules that are potentially employed to treat COVID-19 and other SARS-CoV-2-related

Nitrobenzothiazinones (BTZs) represent a novel type of antitubercular agents targeting DprE1. Two clinical candidates BTZ043 and PBTZ169, as well as many other BTZs showed potent anti-TB activity, but they are all highly lipophilic and their poor aqueous solubility is still a serious issue need to be addressed. Here, we designed and synthesized a series of new BTZ derivatives, wherein a hydrophilic

Nuclear factor erythroid 2-related factor 2 (NRF2) is a crucial transcription factor involved in oxidative stress response, which controls the expression of various cytoprotective genes. Recent research has indicated that constitutively activated NRF2 can enhance patients' resistance to chemotherapy drugs, resulting in unfavorable prognosis. Therefore, the development of NRF2 inhibitors has emerged

Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) regulates programmed cell death and inflammation, contributing to a wide range of human pathologies, including inflammatory disorders, neurodegenerative conditions, and cancer. Despite this, no RIPK1 positron emission tomography (PET) ligand with significant specificity has been reported to date. In this work, we designed and synthesized

Targeting cancer-specific vulnerabilities through synthetic lethality (SL) is an emerging paradigm in precision oncology. A SL strategy based on PARP inhibitors has demonstrated clinical efficacy. Advances in DNA damage response (DDR) uncover novel SL gene pairs. Beyond BRCA-PARP, emerging SL targets like ATR, ATM, DNA-PK, CHK1, WEE1, CDK12, RAD51, and RAD52 show clinical promise. Selective and bioavailable

Natural product evodiamine () and its synthetic derivatives represent an attractive dual Topo 1/2 inhibitors with broad-spectrum antitumor efficacy. However, the clinical applications of these compounds have been impeded by their poor aqueous solubility. Herein, a series of water-soluble 10-substituted-(14)-phenylevodiamine derivatives were designed and synthesized. The most potent compound featuring

In this work, we describe an improved series of -phenylpyrrolamide inhibitors that exhibit potent activity against DNA gyrase and are highly effective against high-priority gram-positive bacteria. The most potent compounds show low nanomolar IC values against DNA gyrase, and in addition, compound also inhibits topoisomerase IV in the nanomolar concentration range, making it a promising candidate for

In this study, a series of novel thieno [3, 2-]pyridinone derivatives were designed and synthesized using a scaffold hopping strategy. Six compounds showed potent anti-mycobacterial activity (minimum inhibitory concentration (MIC) ≤ 1 μg/mL) against (Mtb) UAlRa. Compound displayed good activity against Mtb UAlRv (MIC = 0.5–1 μg/mL). Compounds and also showed activity against Mtb UAlRa in macrophages

Currently, as the largest family of E3 ubiquitin ligases, Skp1-Cullin 1-F-box (SCF) E3 ligase complexes have attracted extensive attention. Among SCF complexes, Skp2, β-TrCP, and FBXW7 have undergone extensive research on their structures and functions. Previous studies suggest Skp2, β-TrCP, and FBXW7 are overexpressed in numerous cancers. Thus, the SCF E3 ligase complex has become a significant target

Leucine-rich repeat kinase 2 (LRRK2) has been reported to be associated with familial and idiopathic Parkinson's disease (PD) risk and is a promising target for drug discovery against PD. To identify novel and effective LRRK2 inhibitors, an ensemble virtual screening strategy by combining fingerprint similarity, complex-based pharmacophore and structure-based molecular docking was proposed and applied

Chikungunya virus (CHIKV) is responsible for the most endemic alphavirus infections called Chikungunya. The endemicity of Chikungunya has increased over the past two decades, and it is a pathogen with pandemic potential. There is currently no approved direct-acting antiviral to treat the disease. As part of our antiviral drug discovery program focused on alphaviruses and the non-structural protein

Alzheimer's disease (AD, also known as dementia) has become a serious global health problem along with population aging, and neuroinflammation is the underlying cause of cognitive impairment in the brain. Nowadays, the development of multitarget anti-AD drugs is considered to be one effective approach. Imidazolylacetophenone oxime ethers or esters () were multifunctional agents with neuroinflammation

Tumor proliferation and metastasis are intricately linked to blood vessel formation, with vascular endothelial growth factor (VEGF) playing a pivotal role in orchestrating angiogenesis throughout tumor progression. Pseudolaric acid B (PAB) has emerged as a potent inhibitor of tumor cell proliferation, migration, and angiogenesis. In efforts to enhance its efficacy, 37 derivatives of PAB were synthesized

Pyridazinone derivatives have been extensively used as anticancer agents. IMB5036 is a structure specific pyridazinone compound with potential antitumor activity via targeting KSRP protein which controls gene expression at multiple levels. In this study, fifteen IMB5036 analogues were synthesized and preliminary structure-activity relationships were explored. Among them, compounds and exhibited remarkably

The rational installation of pharmacophores targeting HSP90 and LSD1 axes has achieved significant anti-cancer capacity in prostate and colorectal cancer. Among the series of hybrids, inhibitor exhibited remarkable anti-proliferative activity against prostate cancer cell lines PC-3 and DU145, with GI values of 0.24 and 0.30 μM, respectively. It demonstrated notable efficacy in combinatorial attack

To achieve malaria eradication, new preventative agents that act differently to front-line treatment drugs are needed. To identify potential chemoprevention starting points we screened a sub-set of the CSIRO Australia Compound Collection for compounds with slow-action activity against . This work identified ,-dialkyl-5-alkylsulfonyl-1,3,4-oxadiazol-2-amines as a new antiplasmodial chemotype (e.g.,

The calcium release activated calcium (CRAC) channel is highly expressed in T lymphocytes and plays a critical role in regulating T cell proliferation and functions including activation of the transcription factor nuclear factor of activated T cells (NFAT), cytokine production and cytotoxicity. The CRAC channel consists of the Orai pore subunit and STIM (stromal interacting molecule) endoplasmic reticulum

The correction of protein folding is fundamental for cellular functionality and its failure can lead to severe diseases. In this context, molecular chaperones are crucial players involved in the tricky process of assisting in protein folding, stabilization, and degradation. Chaperones, such as heat shock proteins (HSP) 90, 70, and 60, operate within complex systems, interacting with co-chaperones both

The technique of antimicrobial therapy action is to stop or slow the growth of bacteria that can kill people, animals, and crops. The most widely used antibacterial agents are antibiotics. Even though these antimicrobial medications are quite effective, there are still certain barriers or challenges in using them effectively. To solve these issues, new antimicrobial drug molecules that don't have side

Beta-amyloid (Aβ), the most pivotal pathological hallmark for Alzheimer's disease (AD) diagnosis and drug evaluation, was recognized by , a high-affinity fluorescent probe developed by rational molecular design. With a TICT mechanism, exhibited remarkable affinity with Aβ aggregates (K = 81.54 nM for oligomers; K = 66.70 nM for fibril) and substantial fluorescence enhancement (F/F = 44), enabling real-time

Herein, we designed and synthesized a series of novel 2-methylthieno []pyrimidine analogues as tubulin inhibitors with antiproliferative activities at low nanomolar levels. Among them, compound displayed the most potent anti-proliferative activity against six cancer cell lines with an average IC of ∼6.23 nM, better than that of colchicine (IC = 9.26 nM). exerted its anti-cancer activity by suppressing

Fibroblast activation protein-α (FAP) has emerged as a promising target in the field of radiopharmaceuticals due to its selective expression in cancer-associated fibroblasts (CAFs) and other pathological conditions involving fibrosis and inflammation. Recent advancements have focused on developing FAP-specific radioligands for diagnostic imaging and targeted radionuclide therapy. This perspective summarized

Enhancing the efficacy of subunit vaccines relies significantly on the utilization of potent adjuvants, particularly those capable of triggering multiple immune pathways. To achieve synergistic immune augmentation by Toll-like receptor 4 agonist (TLR4a) and nucleotide-binding oligomerization-domain-containing protein 2 agonist (NOD2a), in this work, we conjugated RC529 (TLR4a) and MDP (NOD2a) to give

Gastrointestinal (GI) cancers, encompassing a range of malignancies within the digestive tract, present significant challenges in both diagnosis and treatment, reflecting a dire need for innovative therapeutic strategies. This article delves into the profound influence of non-histone methylation on the pathogenesis and evolution of gastrointestinal (GI) cancers. Non-histone proteins, undergoing methylation

Glioma, a common primary brain tumor, is highly infiltrative and invasive, often leading to drug resistance and recurrence. Therefore, the development of novel therapeutic agents is urgently needed. Pseudellone C is a novel marine triindole alkaloid. Screening of its antiproliferative activity against 55 cell lines revealed its anti-CNS cancer potential. A total of 42 derivatives of Pseudellone C were

Ischemic stroke (IS) is a disease of high death and disability worldwide with few medications in clinical treatment. Neuroinflammation and oxidative stress are considered as crucial factors in the progression of IS. In our previous studies, -salicyloyl tryptamine derivative (NST) exhibited promising anti-inflammatory properties and is considered a potential clinical therapy for IS but had limited antioxidant

The diabetes treatment landscape is rapidly evolving towards intelligent and precise therapeutic interventions. Among these advancements, glucose-sensitive microneedle patches (GSMPs), which can automatically adjust the transdermal release rate of insulin based on glucose concentrations, are emerging as a promising strategy. In this work, a new classification method has been proposed for GSMPs, categorizing

The ample peptide field is the best source for discovering clinically available novel antimicrobial peptides (AMPs) to address emerging drug resistance. However, discovering novel AMPs is complex and expensive, representing a major challenge. Recent advances in artificial intelligence (AI) have significantly improved the efficiency of identifying antimicrobial peptides from large libraries, whereas

Tuberculosis (TB), an infectious disease induced by , is one of the primary public health threats all over the world. Since the prevalence of first-line anti-TB agents, the morbidity and mortality issues of TB descended obviously. Nevertheless, the emergences of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains, the double prevalence of HIV-TB co-infection, and the insufficiency

The transcriptional repressor B cell lymphoma 6 (BCL6) plays a critical role in driving tumorigenesis of diffuse large B-cell lymphoma (DLBCL). However, the therapeutic potential of inhibiting or degrading BCL6 for DLBCL has not been thoroughly understood. Herein, we reported the discovery of a series of novel BCL6-targeting PROTACs based on our previously reported -phenyl-4-pyrimidinamine BCL6 inhibitors

New antibacterial compounds are urgently needed, especially for infections caused by the top-priority Gram-negative bacteria that are increasingly difficult to treat. Lipid A is a key component of the Gram-negative outer membrane and the LpxH enzyme plays an important role in its biosynthesis, making it a promising antibacterial target. Inspired by previously reported -methyl-sulfonamidobenzamide-based

PI3K inhibitors have emerged as promising therapeutic agents due to their critical role in various cellular processes, particularly in cancer, where the PI3K pathway is frequently dysregulated. This review explores the evolutionary path of PI3K inhibitors from laboratory discovery to clinical application. The journey begins with early laboratory investigations into PI3K signaling and inhibitor development

Antimicrobial resistance has emerged as a significant threat to global public health. To develop novel, high efficiency antibacterial alternatives to combat multidrug-resistant bacteria, A total of thirty-two novel amphiphilic benzopyran derivatives by mimicking the structure and function of antimicrobial peptides were designed and synthesized. Among them, the most promising compounds and displayed