Letters in Drug Design & Discovery - Volume 15, Issue 10, 2018

Background: A number of novel fluorinated 4,5-dihydropyrazolo [4,3-f][1,2,3] triazolo diazepines (9-11) have been accomplished starting from 1-phenyl-3-trifluoromethyl pyrazole-5-one (3) in a multistep synthesis. Thus obtained compound 9 was converted into corresponding 5-aryl / alkyl fluorinated 4,5-dihydropyrazolo [4,3-f][1,2,3]triazolo diazepinones 10a-j and also 3,5-diaryl / dialkyl fluorinated 4,5-dihydropyrazolo [4,3-f Read More

Background: PI3K/Akt/mTOR was an important signal transduction pathway, activated in tumor cells. The dual inhibitors of mTORC1 and mTORC2 could suppress the tumor growth and angiogenesis by inhibiting the abnormal signal pathway. To deeply understand the structure-activity relationship of urea-morpholinopyrimidine analogues as inhibitors of mTOR, molecular modeling studies include Three-Dimensional Qua Read More

Background: Novel bis(1,4-dihydropyridine) derivatives linked to arene core via ester 5- 7 as well as ether linkages 10-12 were prepared, and their structures were confirmed by several spectral tools. They were evaluated as anticancer agents on A549 and MCF7 cell lines by SRB assay and as antibacterial agents on two gram-positive and two gram-negative bacterial strains by disc diffusion method. Methods: SRB assay shows t Read More

Background: Chronic Myelogenous Leukemia (CML) is a kind of blood and bone marrow cancer. Tyrosine Kinase Inhibitors (TKIs) play an important role in the treatment of Chronic Myelogenous Leukemia (CML). Objective: The aims of this study are to demonstrate the different binding mode of Benzothiazole- Based analogues with T315I mutant Bcr-Abl and wild-type Bcr-Abl. Methods: In this paper, Self-Organizing Molecular Field Read More

Background: Despite availability of variety of antibacterial agents, re-emergance of pathogenic bacteria is still a serious medical concern. Identification of new, safer, and selective antibacterial agents is the key interest in the medicinal chemistry research. Methods: A library of synthetic arylidene nicotinic and isonicotinic hydrazones (1-63) were investigated for antimicrobial activities. Results: A number of derivatives sho Read More

Background: Going through several difficulties in crystallizing GPCRs, deeper understanding of these proteins could be understood through homology modeling and mutational studies. Due to the unavailability of experimentally solved structures, in silico models could gain insights. CCR5 is a pharmaceutically significant GPCR and it has been well-characterized even before its xtal structure. Mutagenesis studies were carrie Read More

Background: Lack of specificity and occurence of resistance to current antibacterial and antifungal agents are major shortcomings for the treatment of microbial diseases. Finding novel antimicrobial agents is therefore highly needed to develop more potent drugs. Within this framework, several indole derivatives were designed and reported in the literature. Methods: In vitro antibacterial and antifungal activiti Read More

Background: Tuberculosis (TB), a contagious airborne disease caused by pathogen Mycobacterium tuberculosis (M. tb) is the second leading cause of death world-wide among the transferable diseases. It is therefore necessary to devote continuing effort for the identification and development of New Chemical Entities (NCEs) as potential antimicrobial agents to address this serious health problem. Methods: A series of new compou Read More

Background: The past decade has witnessed a significant increase in the prevalence of resistance to antibacterial and antifungal agents. To overcome this problem it is desirable to devote continuing effort in evaluating new series of chemical entities for the identification of new antimicrobial agents. Methods: The alkynyl substituted 2-amino-1,4-dihydropyrimidine framework has been explored for the identificatio Read More

Background: Free radicals are unstable molecules with one or more unpaired electrons that can associate and oxidize the biological macromolecules causing damage. The human organism is endowed with antioxidant defenses; however, an imbalance between these defenses and the oxidative stress, derived from excess of free radicals, can trigger the development of diseases. The fighting against free radical Read More

Purpose: The aim of this study was to synthesize a series of symmetrical 2,6- diarylidenecyclohexanones (1-6) and their 6-amino-1,3-dimethyluracil monoadducts (7-10) to evaluate their cytotoxicity in a panel of cell lines. Secondly, to evaluate the effect of the most potent compound on the cell cycle of HeLa cells. Methods: The 2,6-diarylidenecyclohexanones (1-6) were synthesized by the Claisen-Schmidt condensation using cycl Read More