Letters in Drug Design & Discovery - Volume 14, Issue 3, 2017

Background: Glucokinase activators (GKAs) represent a promising opportunity for the treatment of type 2 diabetes due to the fact that glucokinase (GK) is a key regulator of glucose homeostasis. Method: Based on structure-based design strategies, a series of novel orotic acid amide derivatives have been synthesized. Lead optimization led to the discovery of several active compounds via in vitro enzyme assays. Compared to the Read More

Introduction: After using insecticides over many years, the resistance and environmental issues have become great challenges to crop protection. Modern agriculture calls for new insecticidal candidates. Phthalic diamide insecticide containing adjacent two amide group were favored for its new mode of action. Most chemical optimizations of phthalic diamide insecticide focused on amide groups. Modifications on phenyl part inclu Read More

Background: ALK was a receptor tyrosine kinase (RTK) belonging to the insulin receptor superfamily. Many ALK fusion partner genes have been identified in NSCLC, such as NPM, EML4, TFG, KLC1, KIF5B and PTPN3. There had been many reports of potent ALK inhibitors discovered by innovative pharmaceutical companies. Methods: A series of 2,4-diarylaminopyrimidine-containing ALK inhibitors were synthesized by Ki Read More

Background: Metabolic syndrome (MetS) has been recognized as a leading cause of various health complications, affecting many organs including the kidneys. The aim of the current study was to investigate the effect of pentoxifylline (PTX) on the renal dysfunction which is associated with MetS. Methods: MetS was induced in male Wistar rats by adding 10% fructose to their drinking water, as well as placing the animals on a Read More

Background: Tuberculosis is the leading cause of death, especially among the developing countries. Emerging cases of bacilli drug resistance and its co-infection with HIV have led to an increasing occurrence of treatment failure, which drive the need of new and safe drug, having potent anti-TB activity including the drug resistant strains. Method: In the present study, fifteen novel tetrahydroquinoline based propanehydrazides Read More

Background: A 3D-QSAR model of KATP channel activation by benzopyran derivatives has been developed using molecular field alignment method. The model based on pED50 values required for myorelaxant activity by 4, 6 disubstituted benzopyrans has been explored. Discussion: The results are critically discussed based on molecular field of the structures and their alignment with the most potent compound of the series, i.e. Read More

Background: Biotransformed bufadienolides are new kind of cytotoxic products with novel structures. Method: Herein, 3D-QSAR analyses were performed on bufadienolides using CoMFA and CoMSIA to learn the structure-activity relationship and the mechanism of action of these compounds. The cross-validated q2value of CoMFA is 0.648 and q2value of CoMSIA is 0.635. The non-crossvalidated r2 value of CoMFA i Read More

Background: 21 novel 1-alkoxy-1H-benzo[d]-1,2,3-triazole compounds were designed, prepared and evaluated for their antidepressant and anticonvulsant effects in mice. Method: Compound 19 significantly decreased immobility time in the FST without altering the locomotor activity in the open field test, and exhibited higher levels of efficacy than the reference standard fluoxetine. Compound 19 significantly increased 5 Read More

Background: A series of novel 2,6-dichloro-4-(trifluoromethyl)phenyl)-3-(trifluoromethyl) - 1H-pyrazole-4-carboxamide derivatives were designed and synthesized. Method: All the title compounds were confirmed by 1H NMR and MS. Results: The primarily nematicidal activity results indicated that some of them exhibited moderate control efficacy against the tomato root-knot nematode disease caused by Meloidogyne incognita.

Background: Decreased efficiency of artemisinin combination therapy (ACT) and the declining efficacy of affordable drugs for malaria is a major concern with half of the world population living in countries endemic to the disease; hence the development of the next generation anti-malarial drugs is the need of the hour. Objective: The present study is the first attempt to characterize the three dimensional structure of Plasmo Read More

Background: Escherichia coli has an adaptive metabolism and many strains are resistant to classical antibacterial agents, and due to this resistance, it can cause severe clinical infections. In addition, few novel antibacterial agents have been developed in recent years, which corroborate with antimicrobial resistance. For this reason, innovative antimicrobials with novel targets and modes of action are needed. Read More

Backkground: Primaquine thiazolidinone derivatives are proposed as promising antimalarial candidates to be tested as primaquine substitutes. Method: Molecular docking and dynamics simulations were applied in the analogues-NQO2 complexes to understand their interactions, and the toxic potential of these derivatives in a set of 16 target proteins was also studied. Results: The results of our study suggest that the inter Read More

In antiretroviral therapy Integrase Inhibitors (INIs) have become a key component since the approval of raltegravir in 2007 followed by the recent approval of elvitegravir in 2012. The next generation compound dolutegravir has obtained the approval from USFDA in August 2013. Dolutegravir possesses distinct characteristics like prolonged half-life, once-daily dosing without the need for any booster along with no significant eff Read More