title: Novel quinolone substituted thiazolidin-4-ones as anti-inflammatory, anticancer agents: design, synthesis and biological screening.
abstract: Nuclear factor-kappaB (NF-κB) has been reported to regulate various genes involved in cancer and inflammation. Accordingly, drugs suppressing or inhibiting NF-κB may possess both anti-inflammatory and anticancer properties. A library of quinolone substituted thiazolidin-4-ones was docked into the active site of NF-κB and the top-ranked 31 compounds were synthesized and evaluated for anti-inflammatory and anticancer activity. The best-ranked compound 6b showed highest anti-inflammatory activity in carrageenan-induced paw edema model. In vitro anticancer studies revealed 1a and 16a as most active compounds against BT-549, HeLa, COLO-205 and ACHN human cancer cell lines. Compounds 1a and 16a exhibited NF-κB dependent anticancer properties and apoptosis mediated cell death. In vivo Ehrlich ascites carcinoma study further confirmed the antitumor activity of 1a and 16a.
authors.affiliation: Department of Pharmaceutical Chemistry, Manipal College of Pharmaceutical Sciences, Karnataka, Manipal 576104, India.
authors.forename: Sharad Kumar
authors.initials: SK
authors.lastname: Suthar
authors.forename: Varun
authors.initials: V
authors.lastname: Jaiswal
authors.forename: Sandeep
authors.initials: S
authors.lastname: Lohan
authors.forename: Sumit
authors.initials: S
authors.lastname: Bansal
authors.forename: Anil
authors.initials: A
authors.lastname: Chaudhary
authors.forename: Amit
authors.initials: A
authors.lastname: Tiwari
authors.forename: Angel Treasa
authors.initials: AT
authors.lastname: Alex
authors.forename: Alex
authors.initials: A
authors.lastname: Joesph
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002286:Carcinoma, Ehrlich Tumor / Q000517:prevention & control; D002351:Carrageenan; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D008956:Models, Chemical; D008958:Models, Molecular; D015394:Molecular Structure; D016328:NF-kappa B / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D015363:Quinolones / Q000737:chemistry*; D051381:Rats; D053778:Thiazolidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D016328:NF-kappa B; D015363:Quinolones; D053778:Thiazolidines; D002351:Carrageenan