Letters in Drug Design & Discovery - Volume 21, Issue 16, 2024

Discovering new drugs is time-consuming and expensive and involves many different tools from various domains. Numerous omic technologies, such as genomics, transcriptomics, proteomics, and metabolomics, have been created to speed up the process. Leveraging genetic and genomic insights, these methodologies play a pivotal role. Genetic insights aid in target identification, prioritization, and the prediction of drug out Read More

Generally, heterocyclic compounds are included in a large class of pharmacologically active compounds. The indole scaffold in this category is widely distributed in nature and present in many active compounds, especially anti-cancer agents. Due to its unique physicochemical and biological properties, the indole platform has been considered a favorable scaffold in anti-cancer drug design and development. Various indole co Read More

Alzheimer's disease (AD), a central cause of dementia, is characterized by the accumulation of amyloid β-peptide (Aβ) peptides in the brain. P-glycoprotein (P-gp), a highly expressed protein in the BBB, plays a fundamental role in transporting Aβ from the brain to the blood and protecting the blood-brain barrier (BBB). The dysfunction or decreased abundance of this transporting protein is associated with the accumulation Read More

IntroductionThe High-density lipoprotein (HDL) receptor, Scavenger receptor class B, type I (SRBI) plays a crucial role in lipoprotein metabolism, cholesterol homeostasis, and atherosclerosis. In the present study, a quantitative structure-activity relationship study (QSAR) investigation was conducted on a data set of 31 novel indolinyl thiazole-based inhibitors of SR-BI mediated lipid uptake.MethodsTo build the QSAR model, Read More

BackgroundThis study aimed to design and synthesize a series of novel C8-Formononetin derivatives and evaluate their in vitro anti-tumor activity. The experimental results showed that these derivatives exhibited varying degrees of anti-tumor effects on HeLa, A549, and HepG2 cells, and compound 8, in particular, showed excellent inhibitory activity against HepG2 cell growth, which surpassed that of 5-FU.MethodsImporta Read More

BackgroundPDE5 inhibitors have had a surge in popularity over the last decade owing to their efficacy in the treatment of erectile dysfunction, coronary vasculopathy, and pulmonary arterial hypertension. These inhibitors exhibit competitive binding with phosphodiesterase type 5 and inhibit the hydrolysis of cyclic guanosine monophosphate, hence elevating the levels of cGMP in smooth muscle cells and prolonging the durati Read More

BackgroundA series of 2-arylbenzimidazole derivatives were designed and developed as antidiabetic drugs using 2D and 3D QSAR, molecular docking and ADME studies.MethodsAll molecular modeling studies were performed using Molecular Design Suite V-Life MDS software. New chemical entities (NCEs) were designed based on the results of 2D and 3D QSAR studies. Docking studies were performed with the desig Read More

BackgroundMcl-1 is a kind of antiapoptotic protein and its overexpression is closely related to the occurrence of cancer. Aryl sulfonamide derivatives are expected to become new anticancer agents due to their high inhibitory activity on the Mcl-1 protein.ObjectiveThe study aimed to establish the QSAR model with good prediction ability and elaborate the influence of structure and chirality on the inhibitory activity.Met Read More

IntroductionInhibitors of topoisomerases, essential regulators of cancer development, are promising as cancer treatments. These enzymes regulate DNA topology and eliminate topological constraints during various biological processes, including replication, transcription, and recombination. Nature has continually offered scientists pathways to explore the development of new drugs. Indeed, since ancient times Read More

ObjectiveHypertension is one of the main causes of chronic kidney disease. Astragalus membranaceus (AM), an important traditional Chinese medicine for treating hypertensive nephropathy, has a complex composition that makes it challenging to explore its mechanism of action and limits its clinical application. This study aims to investigate the underlying mechanism of AM in treating hypertensive nephropathy.MethodsWe Read More

BackgroundPrevalence of microbial resistance due to Metallo-β-lactamase (MBL) enzyme pose a serious threat to human life. MBLs depend on active site zinc for their hydrolytic activity; hence, the investigation of zinc chelators emerged as an attractive strategy for the development of potent MBL inhibitors.MethodsTo prove that such chelators selectively target MBLs, in the present investigation, novel cephalosporins ba Read More

BackgroundCandida albicans is the yeast that causes the fungal infection known as candidiasis. One of the standard methods for treating candida is the application of fluconazole. The low solubility of fluconazole in aqueous media is a big problem in the use of this agent. Novel drug delivery systems, such as microemulsions, could be applied to solve this problem. The main aim of this study was to perform statistical optimizati Read More

BackgroundHedyotis diffusa Willd (HDW) is an herb that has been used empirically for treating cancer, and its antileukemic effect has been confirmed by laboratory evidence. This study aimed to explore the underlying mechanism by which HDW and its active compound exert effects on acute myeloid leukemia (AML) through in silico analyses combined with experimental validation.MethodsThe targets of the compounds Read More

BackgroundThe histone deacetylase family of proteins, which includes the sirtuins, participates in a wide range of cellular processes, and is intimately involved in neurodegenerative illnesses. The research on sirtuins has garnered a lot of interest. However, there are currently no effective therapeutic drugs.MethodsIn order to explore the potential inhibitors of SIRTs, we first screened four potential lead compounds of SIRT2 i Read More

BackgroundAlthough indazole derivatives are rare and may not be available easily in nature, there are many reports demonstrating their pharmaceutical and other applications.ObjectiveThis study aimed to synthesize new indazole derivatives and evaluate their anti-proliferative activity to produce new anti-cancer agents.MethodsCompounds 3a-c were synthesized through the reaction. The 2-aryllidenecyclohexane-1,3-di Read More

BackgroundMetastatic Castration-resistant Prostate Cancer (mCRPC) represents a critical challenge in current prostate cancer treatment. Benzimidazole Derivative XY123 has emerged as a novel inhibitor for its treatment.ObjectiveThis study aims to establish a robust Quantitative Structure-Activity Relationship (QSAR) model for predicting the activity of Benzimidazole Derivative XY123 derivatives, aiding the develo Read More

BackgroundThirteen derivatives were designed and synthesized based on the excellent lead compound Matrine.ObjectiveThis study aimed to discover novel anticancer agents with superior anticancer activity and to support the discovery of new drugs.MethodsThe in vitro antiproliferative activity of all derivatives against four human cancer cells, A549, HGC-27, HCT-116, and HeLa, was determined by MTT. The best active c Read More

BackgroundInvestigating the structural attributes of the murine beta3-adrenergic receptor (β3-AR) is imperative for comprehending metabolic regulation, given its close resemblance to the human β3-AR. This receptor holds promise as a target for novel drug development against obesity and diabetes. Despite its potential, the absence of knowledge regarding the structure of murine β3-AR hampers a comprehensive under Read More