title: Synthesis and Anti-cancer Activity of Novel Thiazolidinone Analogs of 6-Aminoflavone.
abstract: Novel heterocyclic analogs were synthesized by combining a flavone nucleus and thiazolidinone ring in an effort to potentiate the existing anti-cancer activity of flavone. The syntheses of 6-aminoflavone, 6-amino-3-methoxyflavone, 6-amino-3-methoxy-3',4'-dimethxyflavone and their corresponding thiazolidinone analogs were performed. Fifteen novel analogs were synthesized and evaluated for their anti-cancer activity using cell-based assay techniques and in vivo testing. As expected, the analogs improved cytotoxicity and were shown to increase the life span of cancer-bearing mice. Cytotoxicity was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assays in HeLa, MDA-MB-435, and Vero cell lines. In vivo evaluation of anti-cancer activity performed in albino mice bearing Dalton's ascites carcinoma showed that the new analogs enhanced life span and prevented increases in body weight owing to tumor volumes. Moreover, cell-cycle analysis and Hoechst staining analysis proved the apoptotic potential of these analogs. Preliminary pharmacokinetic evaluation was carried out on the synthesized compounds to determine the lipophilicity and pKa. Lipophilicity was determined using high-performance liquid chromatography and the results showed a direct correlation between the observed anti-cancer activity and log P value, while pKa values indicated the ionizing range which is a prediction tool for solubility and permeability.
authors.affiliation: Department of Pharmaceutical Chemistry, Manipal College of Pharmaceutical Sciences, Manipal University.
authors.forename: Sudheer
authors.initials: S
authors.lastname: Moorkoth
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002522:Chlorocebus aethiops; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D013329:Structure-Activity Relationship; D013830:Thiadiazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D014709:Vero Cells
chemical_list: D000970:Antineoplastic Agents; D005419:Flavonoids; D013830:Thiadiazoles; C413760:aminoflavone