Letters in Drug Design & Discovery - Volume 16, Issue 2, 2019

Background: With the approval of gefitinib, erlotinib, afatinib, and osimertinib for clinical use, targeting Epidermal Growth Factor Receptor (EGFR) has been intensively pursued. Similar to most therapies, challenges related to the treatment resistance against these drugs have emerged over time, so new EGFR Tyrosine Kinase Inhibitors (TKIs) need to be developed. This study aimed to investigate the potential use of a series of Read More

Background: The synthesis of 2-[3/4-((6-substituted-1-oxo-2,3-dihydro-1H-inden-2- ylidene)methyl)phenoxy]-N-(heteroaryl)acetamide derivatives and the investigation of their anticancer activity were studied. Methods: 2-(3/4-Hydroxybenzylidene)-6-substituted-2,3-dihydro-1H-inden-1-ones were reacted with suitable 2-chloroacetamides to give 2-[3/4-((6-substituted-1-oxo-2,3-dihydro-1H-inden-2-ylidene) methyl)phenoxy]-N-( Read More

Background: We report here an efficient synthesis of new Mannich products 4(a-m) in excellent yields via multi-component reaction for the condensation of 5-bromothiophene- 2-carboxaldehyde (5-BT-2C), 2,4-dihydroxybenzophenone (2,4-DHBP) and primary/secondary amine derivative using Ethyl Ammonium Nitrate (EAN) as ionic liquid, which is reusable and plays an important role as a catalyst under 800C. Methods: All Read More

Background: The impact of the ubiquitous dietary phenolic compound p-coumaric acid on human breast cancer cells was assessed, through a multidisciplinary approach: Combined biological assays for cytotoxicity evaluation and biochemical profiling by Raman microspectroscopic analysis in cells. Methods: Para-coumaric acid was shown to exert in vitro chemoprotective and antitumor activities, depending on the concentra Read More

Background: Aurora kinases perform important roles in mammals, mainly in cell cycle. Overexpression of these enzymes is related to tumor development and is indicative of worsening of clinical conditions. Aurora kinases are promising targets in the search for new anticancer drugs, in particular, Aurora B. Methods: This work was designed to study and understand the interactions between human Aurora B and several in Read More

Background: Acquired Immunodeficiency Syndrome (AIDS) caused by Human Immunodeficiency Virus (HIV) has seriously threatened human health, so development of new, selective and safe non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) remains a high priority for medical research. Diaryltriazine (DATA) have been identified as a new class of potent nonnucleoside HIV-1 Reverse Transcriptase (RT) inhibitors. Read More

Background: 2,4-disubstituted-1,3-thiazole derivatives (2a–j), (3a–f) and (4a–f) were synthesized, characterized and screened for their potential as antimicrobial agents. In the preliminary screening against a panel of bacterial strains, nine compounds showed moderate to potent antibacterial activity (IC50 = 13.7-90.8 μg/ml). Methods: In the antifungal screening, compound (4c) displayed potent antifungal activity (IC50 = 26.5 Read More

Abstract: Background: Chlamydiae are widespread Gram-negative bacteria that cause a number of human diseases. Chlamydia trachomatis is the most prevalent sexually transmitted bacterial pathogen. Methods: Fourteen novel phenazine derivatives were efficiently synthesized via Buchwald-Hartwig cross coupling reaction and Suzuki reaction from 4-bromo-1-methoxyphenazine. All the derivatives displayed antichlamydial acti Read More

Background: Cancer caused nearly 8.8 million deaths in 2015. Limited efficacy, selectivity, drug resistance and toxicity are major complications associated with chemotherapy, potentiating the discovery of anticancer agents. Methods: A new series of N-(7-hydroxy-4-methyl-2-oxoquinolin-1(2H)-yl)acetamide/benzamide analogues (5a-j) was prepared from the precursor, 7-hydroxy-4-methyl-2H-chromen-2-one (3), as antica Read More

Background: Polymorphonuclear neutrophils (PMNs) play a crucial role in the innate immune system's response to microbial pathogens through the release of reactive nitrogen species, including Nitric Oxide (NO). Methods: In neutrophils, NO is produced by the inducible Nitric Oxide Synthase (iNOS), which is regulated by various signaling pathways and transcription factors. N-nitrosodimethylamine (NDMA), a potential human c Read More

Background: In attempts to discover new antiangiogenic entities, a novel series of thioethers derived from 6-thioxo-6,7-dihydro-1H-pyrazolo[3,4-d]pyrimidine-4(5H)ones was considered and designed. Methods: Virtual screening was carried out through docking of the compounds into the vascular endothelial growth factor and matrix metalloproteinase-9 binding sites. Molecular docking studies were performed using Lamar Read More

Background: A new series of 1,2,3-triazol-nitrostyrene derivatives was designed, synthesized, and evaluated for cytotoxic activity against Hep-2 and L929 cell lines. Methods: The synthetic procedure started from the functionalization of 4-hydroxybenzaldehyde with propargyl bromide and a subsequent click reaction to give 1,2,3-triazole derivatives. Then, the reaction of the mentioned derivatives with nitromethane led to the Read More

Background: For the development of suitable lead molecules to different diseases is a highly challenging task for medicinal chemists. Nowadays, hybrid pharmacophore concept has developed as a useful structural modification tool in the drug design of new drug candidates for different diseases. Hybrid pharmacophore approach consists of combination of two or more pharmacophoric moieties from different biologically Read More