Rational design, synthesis, anti-HIV-1 RT and antimicrobial activity of novel 3-(6-methoxy-3,4-dihydroquinolin-1(2H)-yl)-1-(piperazin-1-yl)propa n -1-one derivatives

• Published in: Bioorganic chemistry Vol. 67; pp. 75 - 83
• Main Authors: Chandera, Subhash, Wangb, Ping, Ashoka, Penta, Yangb, Liu-Meng, Zhengb, Yong-Tang, Murugesana, Sankaranarayanan
• Format: Journal Article
• Language: English
• Published: 01.08.2016
• Subjects: Aspergillus niger; Bacillus cereus; Candida albicans; Escherichia coli; Human immunodeficiency virus; Human immunodeficiency virus 1; Lentivirus; Pseudomonas putida; Staphylococcus aureus
• ISSN: 0045-2068
• DOI: 10.1016/j.bioorg.2016.05.009

In the present study, fifteen novel 3-(6-methoxy-3,4-dihydroquinolin-1(2H)-yl)-1-(piperazin-1-yl)propa n -1-one (6a-o) derivatives were designed as inhibitor of HIV-1 RT using ligand based drug design approach and in-silico evaluated for drug-likeness properties. Designed compounds were synthesized, characterized and in-vitro evaluated for RT inhibitory activity against wild HIV-1 RT strain. Among the tested compounds, four compounds (6a, 6b, 6j and 6o) exhibited significant inhibition of HIV-1 RT (IC sub(50) [el] 10 mu g/ml). All synthesized compounds were also evaluated for anti-HIV-1 activity as well as cytotoxicity on T lymphocytes, in which compounds 6b and 6l exhibited significant anti-HIV activity (EC sub(50) values 4.72 and 5.45 mu g/ml respectively) with good safety index. Four compounds (6a, 6b, 6j and 6o) found significantly active against HIV-1 RT in the in-vitro assay were in-silico evaluated against two mutant RT strains as well as one wild strain. Further, titled compounds were evaluated for in-vitro antibacterial (Escherichia coli, Pseudomonas putida, Staphylococcus aureus and Bacillus cereus) and antifungal (Candida albicans and Aspergillus niger) activities.