title: Design, synthesis and biological evaluation of novel triazole, urea and thiourea derivatives of quinoline against Mycobacterium tuberculosis.
abstract: 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.
authors.affiliation: Institute of Molecular Medicine, Pune, India.
authors.forename: Ram Shankar
authors.initials: RS
authors.lastname: Upadhayaya
authors.forename: Girish M
authors.initials: GM
authors.lastname: Kulkarni
authors.forename: Nageswara Rao
authors.initials: NR
authors.lastname: Vasireddy
authors.forename: Jaya Kishore
authors.initials: JK
authors.lastname: Vandavasi
authors.forename: Shailesh S
authors.initials: SS
authors.lastname: Dixit
authors.forename: Vivek
authors.initials: V
authors.lastname: Sharma
authors.forename: Jyoti
authors.initials: J
authors.lastname: Chattopadhyaya
mesh_terms: 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
chemical_list: D000995:Antitubercular Agents; D001426:Bacterial Proteins; D011804:Quinolines; D014230:Triazoles; D014508:Urea; D025181:ATP Synthetase Complexes; D013890:Thiourea