Design, synthesis and biological evaluation of novel triazole, urea and thiourea derivatives of quinoline against Mycobacterium tuberculosis.
A new series of 20 quinoline derivatives possessing triazolo, ureido and thioureido substituents have been synthesized and their antimycobacterial properties have been evaluated. Compounds 10, 22 and 24 inhibited Mycobacterium tuberculosis H37Rv up to 96%, 98% and 94% respectively, at a fixed concentration of 6.25 microg/mL. Minimum inhibitory concentration of 3.125 microg/mL was obtained for compound 10 and 24, while for compound 22 it was 6.25 microg/mL. Molecular docking calculations suggest critical hydrogen bonding and electrostatic interactions between polar functional groups (such as quinoline-nitrogen, urea-carbonyl and hydroxyl) of anti-mycobacterial (anti-TB) compounds and amino acids (Arg186 and Glu61) of ATP-synthase of M. tuberculosis, could be the probable reason for observed anti-mycobacterial action.
Upadhayaya
Ram Shankar
RS
Institute of Molecular Medicine, Pune, India.
Kulkarni
Girish M
GM
Vasireddy
Nageswara Rao
NR
Vandavasi
Jaya Kishore
JK
Dixit
Shailesh S
SS
Sharma
Vivek
V
Chattopadhyaya
Jyoti
J
D025181:ATP Synthetase Complexes / Q000378:metabolism*; D000818:Animals; D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D008264:Macrophages / Q000166:cytology; D008958:Models, Molecular; D015394:Molecular Structure; D051189:Murinae; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000502:physiology; D011485:Protein Binding; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013890:Thiourea / Q000031:analogs & derivatives; D014230:Triazoles / Q000737:chemistry; D014376:Tuberculosis / Q000188:drug therapy; D014508:Urea / Q000031:analogs & derivatives
D000995:Antitubercular Agents; D001426:Bacterial Proteins; D011804:Quinolines; D014230:Triazoles; D014508:Urea; D025181:ATP Synthetase Complexes; D013890:Thiourea