Novel amidino substituted 2-phenylbenzothiazoles: synthesis, antitumor evaluation in vitro and acute toxicity testing in vivo.
The efficient synthesis of new bis-substituted nitro-amidino, amino-amidino (10a, 10b-13a, 13b) and previously prepared diamidino 2-phenyl-benzothiazoles (9a, 9b) is described. The compounds 11a and 11b were prepared by recently developed methodology of the key precursors in zwitterionic form 8a and 8b with 4-nitrobenzoylchloride in a very good yield (70%). All compounds except diamidino-substituted 2-phenylbenzothiazole 9a show exceptionally prominent tumor cell-growth inhibitory activity and cytotoxicity, whereby the special selectivity of amino-amidine 2-phenylbenzothiazole 12a towards MCF-7 and H 460 cells makes this compound a prospective lead compound that should be further evaluated in animal models. All in vivo tested compounds (12a, 12b, 13a and 13b) are absorbed from mice gastrointestinal system. LD(50) are between 67.33 and 696.2mg/kg body weight (OECD/EPA toxicity categories 2-3).
Racané
Livio
L
Department of Applied Chemistry, Faculty of Textile Technology, University of Zagreb, baruna Filipovića 10000 Zagreb, Croatia.
Kralj
Marijeta
M
Suman
Lidija
L
Stojković
Ranko
R
Tralić-Kulenović
Vesna
V
Karminski-Zamola
Grace
G
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D007928:Lethal Dose 50; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000188:drug therapy; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity
D000970:Antineoplastic Agents; D013844:Thiazoles; C070845:2-phenylbenzothiazole