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.
Department of Studies in Chemistry, Karnatak University, Pavate Nagar, Dharwad 580003, Karnataka, India.
Ashish
A
Anand
Department of Studies in Chemistry, Karnatak University, Pavate Nagar, Dharwad 580003, Karnataka, India.
Reshma J
RJ
Naik
Department of Studies in Chemistry, Karnatak University, Pavate Nagar, Dharwad 580003, Karnataka, India.
Hrishikesh M
HM
Revankar
Department of Studies in Chemistry, Karnatak University, Pavate Nagar, Dharwad 580003, Karnataka, India. Electronic address: manohar274@gmail.com.
Manohar V
MV
Kulkarni
Novel Drug Design and Discovery Laboratory, Department of Pharmaceutical Chemistry, S. E. T's College of Pharmacy, Sangolli Rayanna Nagar, Dharwad 580002, Karnataka, India.
Sheshagiri R
SR
Dixit
Novel Drug Design and Discovery Laboratory, Department of Pharmaceutical Chemistry, S. E. T's College of Pharmacy, Sangolli Rayanna Nagar, Dharwad 580002, Karnataka, India.
Shrinivas D
SD
Joshi
D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D057930:Click Chemistry; D003374:Coumarins / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D021281:Quantitative Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
D000995:Antitubercular Agents; D003374:Coumarins; D014230:Triazoles
1,2,3 triazoles; 2H-chromen-2-one; 3D-QSAR; Anti-tubercular; Click reaction; Molecular docking; Surflex-dock