Novel tetrazoloquinoline-rhodanine conjugates: Highly efficient synthesis and biological evaluation

Dnyaneshwar D Subhedar; Mubarak H Shaikh; Laxman Nawale; Amar Yeware; Dhiman Sarkar; Firoz A Kalam Khan; Jaiprakash N Sangshetti; Bapurao B Shingate

doi:10.1016/j.bmcl.2016.03.045

Novel tetrazoloquinoline-rhodanine conjugates: Highly efficient synthesis and biological evaluation

Bioorg Med Chem Lett. 2016 May 1;26(9):2278-83. doi: 10.1016/j.bmcl.2016.03.045. Epub 2016 Mar 15.

Authors

Dnyaneshwar D Subhedar¹, Mubarak H Shaikh¹, Laxman Nawale², Amar Yeware², Dhiman Sarkar², Firoz A Kalam Khan³, Jaiprakash N Sangshetti³, Bapurao B Shingate⁴

Affiliations

¹ Department of Chemistry, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad 431 004, India.
² Combichem Bioresource Center, Organic Chemistry Division, CSIR-National Chemical Laboratory, Pune 411 008, India.
³ Department of Pharmaceutical Chemistry, Y. B. Chavan College of Pharmacy, Rafiq Zakaria Campus, Aurangabad 431 001, India.
⁴ Department of Chemistry, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad 431 004, India. Electronic address: bapushingate@gmail.com.

PMID: 27013391
DOI: 10.1016/j.bmcl.2016.03.045

Abstract

In search of new active molecules against Mycobacterium tuberculosis (MTB) H37Ra and Mycobacterium bovis BCG, a small focused library of rhodanine incorporated tetrazoloquinoline has been efficiently synthesized by using [HDBU][HSO4] acidic ionic liquid. The compound 3c found to be promising inhibitor of MTB H37Ra and M. bovis BCG characterized by lower MIC values 4.5 and 2.0 μg/mL, respectively. The active compounds were further tested for cytotoxicity against HeLa, THP-1, A549 and PANC-1 cell lines using MTT assay and showed no significant cytotoxic activity at the maximum concentration evaluated. Again, the synthesized compounds were found to have potential antifungal activity. Furthermore, to rationalize the observed biological activity data, the molecular docking study also been carried out against a potential target Zmp1 enzyme of MTB H37Ra, which revealed a significant correlation between the binding score and biological activity for these compounds. The results of in vitro and in silico study suggest that these compounds possess ideal structural requirement for the further development of novel therapeutic agents.

Keywords: Antifungal; Antitubercular; Cytotoxicity; Docking study; Rhodanine derivatives.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Quinolines / chemical synthesis*
Quinolines / chemistry
Quinolines / pharmacology*
Rhodanine / chemistry*

Substances

Quinolines
Rhodanine