Letters in Drug Design & Discovery - Volume 20, Issue 12, 2023

Ferroptosis is an identified form of regulated cell death different from cell necrosis, autophagy, and apoptosis, characterized by iron-dependent accumulation of lipid reactive oxygen species. The processes of ferroptosis are mainly related to iron metabolism disorder, inactivation of glutathione peroxidase 4 (GPX4), and coenzyme Q10-dependent pathway. Inducing ferroptosis is considered a promising strategy to figh Read More

Background: Curcumin is a polyphenol compound extracted from plant turmeric with high pharmacological activities. The clinical application of curcumin is limited due to the shortcomings of poor water solubility, instability, and low bioavailability. Objective: Modifying the 4', 4''-bit of curcumin is an effective strategy to improve the pharmacological activity of curcumin. Conclusion: In this review, we focused on the strategy of sy Read More

Introduction: Tuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb), has its natural history tracing back to 70,000 years. Latent M.tb infection is the reservoir of the TB epidemic. M.tb is becoming more prevalent and acquiring multidrug resistance among the first-line antibiotics. Methods: Methylation is one of the main mechanisms through which bacteria develop resistance, hence targeting methyltransferases pr Read More

Background: Torpedo californica acetylcholinesterase (TcAChE) is an important drug development target for Alzheimer's disease (AD) therapeutics. The current in silico study aims to recognise indene methylene-derived compounds acting against TcAChE to gain insight into the molecular interactions. Objective: The current study focused on identifying novel inhibitors for Torpedo californica acetylcholinesterase (TcAChE) by Read More

Background: The research based on natural product herbicides has been increasingly attractive in the field of agriculture. 4-hydroxyphenylpyruvate dioxygenase (HPPD) is one of the most promising compounds in the field of herbicide innovation. Objective: This paper aims to study the relationship between the activity and structure of quinazoline- 2,4-dione derivatives, and to design novel HPPD inhibitors. Methods: A set Read More

Background: Miltefosine (MIL), hexadecyl phosphocholine, is the only oral medicine used to treat leishmaniasis. This drug has a major limitation and is expensive and potentially teratogenic. Objective: This study aimed to evaluate the toxic effect of MIL and its niosomal form on human umbilical vein endothelial cells (HUVECs), the expression genes, and the profile associated with apoptosis in the mitochondrial permeabilization re Read More

Background: Alzheimer's disease (AD) is one of the major causes of morbidity, affecting more than 36 million population worldwide. Current anti-AD treatments result in limited therapeutic outcomes owing to the complexity of the disease. Some natural promising herbal drugs and phytoconstituents utilized as an alternative treatment for AD have been reported by several researchers for their neuroprotective action Read More

Objective: The aim of this study was to determine the vasorelaxant effect of semisynthetic derivatives of ursolic acid, establish the mode of action, and determine the antihypertensive effect of the most active compound. Methods: Isolated aorta rat rings (ex vivo assay), with and without endothelium, were used to determine the vasorelaxant effect of seven semisynthetic derivatives of ursolic acid (UA-01 to UA-07). Then, Read More

Background: The epidermal growth factor receptor of the tyrosine kinase family has been largely targeted in mutations associated with non-small cell lung cancer. EGFR inhibitors have been produced that bind allosterically to the C797S mutant EGFR enzyme. Objective: Here, the Waterswap tool has been used for the interpretation and visualization of trajectories of mutant EGFR-ligand complexes. Virtual screening of the gen Read More

Background: Predicting protein-peptide binding affinity is one of the leading research subjects in peptide drug design and repositioning. In previous studies, models constructed by researchers just used features of peptide structures. These features had limited information and could not describe the proteinpeptide interaction mode. This made models and predicted results lack interpretability in pharmacy and biology, which led to Read More

Isoxazole derivatives are one of the heterocyclic structures that have various biological activities. Objective: This study aimed to design and synthesize novel isoxazole derivatives and evaluate their cytotoxic, cyclooxygenase (COX) inhibitory, and antimicrobial activities. Methods: Coupling reactions of aniline derivatives and isoxazole carboxylic acid have been established to synthesize chloro-fluorophenyl-isoxazole carboxa Read More

Background: Buruli ulcer (BU), caused by Mycobacterium ulcerans is a neglected tropical disease characterized by necrotic skin lesions. Antibiotic therapy and excision of the lesions are the treatments for this chronic disease. During the management of the disease, the emergence of drug resistance in these bacilli is a major challenge. Therefore, there is a need to identify new drug targets against this important pathogen. Read More

Aims: Synthesis of 4-fluorobenzohydrazide Schiff bases and 1,3,4-oxadiazole analogs has a DPPH radical scavenging potential. Background: Synthetic antioxidants are widely used because they are effective and cheaper than natural antioxidants. Based on the literature survey, this present study is mainly focused on the study of the free radical scavenging activity of the Schiff base and oxadiazole motifs. Methods: In Read More

Background: Cancer still remains a disease of concern with various side effects of synthetic chemotherapeutic agents. Hence, there is a continued need to develop safer therapies with fewer side effects. Erythroxylum species is a widely available source of various phytoconstituents, especially terpenoids. Objective: To carry out the docking studies of a few terpenoids on validated targets like EGFR, VEGFR, CDK, and tubulin prote Read More

Background: Prediction of toxicity of imidazo[4,5-b]pyridine derivatives is carried out using GA-MLR and BPANN methods. Objective: A quantitative structure-property relationship (QSPR) was determined based on methods, including genetic algorithm-multiple linear regression (GA-MLR) and backpropagation artificial neural network (BP-ANN). These methods were employed for modeling and predicting the anticancer potency Read More

Background: Targeting intracellular signaling molecules in nervous tissue progenitors is a promising basis for the development of novel neurodegenerative disease therapy approaches. Naphthoquinone shikonin from the root of Lithospermum erythrorhizon is known to have inhibitory effects on NF-ΚB and STAT3. Objective: This study aimed to explore the influence of shikonin on the functioning of progenitors of nervou Read More

Background: Flavones are potential anticancer agents that act by different mechanisms and have multiple targets to exert anticancer effects. Nitrogen-containing heterocyclic rings have remarkable chemical characteristics as well as a wide range of biological activities. Substitution of the N-heterocyclic ring on the flavon structure may potentiate its anticancer effect. Objective: A series of flavon derivatives with an N-heter Read More

Background: Breast cancer is one of the most common malignant tumors. Signal transduction and activators of transcription 3 (STAT3) have been demonstrated to play important roles in breast cancer. However, no direct inhibitor of STAT3 has been approved by the FDA for clinical use. Objective: LL1 is a newly designed STAT3 inhibitor that we identified. In this study, we investigated the cytotoxic effect of LL1 on breast c Read More