A click chemistry approach for the synthesis of mono and bis aryloxy linked coumarinyl triazoles as anti-tubercular agents

Ashish Anand; Reshma J Naik; Hrishikesh M Revankar; Manohar V Kulkarni; Sheshagiri R Dixit; Shrinivas D Joshi

doi:10.1016/j.ejmech.2015.10.019

A click chemistry approach for the synthesis of mono and bis aryloxy linked coumarinyl triazoles as anti-tubercular agents

Eur J Med Chem. 2015 Nov 13:105:194-207. doi: 10.1016/j.ejmech.2015.10.019. Epub 2015 Oct 22.

Authors

Ashish Anand¹, Reshma J Naik¹, Hrishikesh M Revankar¹, Manohar V Kulkarni², Sheshagiri R Dixit³, Shrinivas D Joshi³

Affiliations

¹ Department of Studies in Chemistry, Karnatak University, Pavate Nagar, Dharwad 580003, Karnataka, India.
² Department of Studies in Chemistry, Karnatak University, Pavate Nagar, Dharwad 580003, Karnataka, India. Electronic address: manohar274@gmail.com.
³ Novel Drug Design and Discovery Laboratory, Department of Pharmaceutical Chemistry, S. E. T's College of Pharmacy, Sangolli Rayanna Nagar, Dharwad 580002, Karnataka, India.

PMID: 26491982
DOI: 10.1016/j.ejmech.2015.10.019

Abstract

A series of mono and bis-triazole coumarin hybrids 6a-u and 9a-f respectively have been synthesized using 4-(azidomethyl)-2H-chromen-2-ones 5a-i and aryl propargyl ethers 2a-c/8 employing Click chemistry modified protocol for Azide-Alkyne cycloadditions(CuAAC). Anti-tubercular screening showed moderate activity for mono aryloxy compounds 6a-u with MIC 50-100 μg/mL, whereas the bis compounds 9a-f were more effective with MICs between 0.2 and 12.5 μg/mL. Molecular modeling and 3D-QSAR measurements using CoMFA and Topomer CoMFA further supported the observed results. The bis compound 9b showed excellent activity with MIC value as low as 0.2 μg/mL.

Keywords: 1,2,3 triazoles; 2H-chromen-2-one; 3D-QSAR; Anti-tubercular; Click reaction; Molecular docking; Surflex-dock.

Publication types

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

MeSH terms

Antitubercular Agents / chemical synthesis*
Antitubercular Agents / chemistry
Antitubercular Agents / pharmacology*
Click Chemistry*
Coumarins / chemical synthesis
Coumarins / chemistry*
Coumarins / pharmacology*
Dose-Response Relationship, Drug
Microbial Sensitivity Tests
Molecular Structure
Mycobacterium tuberculosis / drug effects*
Quantitative Structure-Activity Relationship
Triazoles / chemical synthesis
Triazoles / chemistry*
Triazoles / pharmacology*

Substances

Antitubercular Agents
Coumarins
Triazoles