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

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. Showing click chemistry approach for the synthesis of mono and bis coumarinyl triazoles. [Display omitted] •Synthesis and characterization of mono and bis coumarinyl triazoles.•Formation of 1,4 isomer under Cu(I) Click conditions.•Anti-tubercular results for the bis triazoles were good-excellent.•Docking & 3D-QSAR shows bis triazoles is effective than mono-triazoles.