title: Anticancer activity of 5-benzylidene-2-phenylimino-1, 3-thiazolidin-4-one (BPT) analogs.
abstract: We recently identified two compounds of 5-benzylidene-2-phenylimino-1,3-thiazolidin-4-one (BPT) analog, 5-(4-methylbenzylidene)-2-phenylamino-1,3-thiazolidin-4-one (MMPT) and 5-(2,4-dihydroxybenzylidene)-2-phenylimino-1,3-thiazolidin-4-one (DBPT), that can effectively induce apoptosis in cancer cells but not in normal cells, independently of P-glycoprotein status. To further investigate the antitumor activity of BPT analogs, we obtained 18 commercially available analogs of BPT and synthesized 7 analogs in our lab, and analyzed their antitumor activity in various cancer cells, including paclitaxel- and vinorelbine-sensitive and -resistant human lung cancer cells. Two of the compounds were more potent than MMPT or DBPT in induction of apoptosis in certain cancer cell lines and remained tumor selective. Seven compounds did not induce any cytotoxic effects in any of the cell lines tested at the highest concentration tested (31 microM). The other compounds induced cytotoxic effects in some cancer cells but not in others or were less potent than MMPT and DBPT. Cell uptake studies showed that analogs that effectively induced cell killing in paclitaxel- and vinorelbine-resistant cells could be taken up easily by those cells despite their high levels of P-glycoprotein expression. These data further demonstrate that thiazolidinone analogs are not P-glycoprotein substrates and could be useful for treatment of P-glycoprotein overexpressing refractory cancers.
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Unit 445, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA.
authors.forename: S
authors.initials: S
authors.lastname: Wu
authors.forename: W
authors.initials: W
authors.lastname: Guo
authors.forename: F
authors.initials: F
authors.lastname: Teraishi
authors.forename: J
authors.initials: J
authors.lastname: Pang
authors.forename: K
authors.initials: K
authors.lastname: Kaluarachchi
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.forename: J
authors.initials: J
authors.lastname: Davis
authors.forename: F
authors.initials: F
authors.lastname: Dong
authors.forename: B
authors.initials: B
authors.lastname: Yan
authors.forename: B
authors.initials: B
authors.lastname: Fang
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017239:Paclitaxel; D013329:Structure-Activity Relationship; D053778:Thiazolidines / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D014747:Vinblastine / Q000031:analogs & derivatives; D000077235:Vinorelbine
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D053778:Thiazolidines; D014747:Vinblastine; D017239:Paclitaxel; D000077235:Vinorelbine