Synthesis and antitumor activity of optically active thiourea and their 2-aminobenzothiazole derivatives: a novel class of anticancer agents.
A novel series of optically active 2-aminobenzothiazole derivatives were synthesized by reaction of optically active amine (I) with thiophosgene to obtain optically active isothiocyanates (IIa-h) which on condensation with 4-fluoro-3-chloro aniline (III) yielded various optically active thioureas (IVa-h). Further oxidative cyclisation in the presence of bromine and chloroform yielded title compounds (Va-h). The structures of these compounds were established by IR, (1)H NMR, (13)C NMR, Mass and HRMS. The compounds (IVa-h and Va-h) were evaluated for in vitro cytotoxicity against mouse Ehrlich Ascites Carcinoma (EAC) and two human cancer cell lines (MCF-7 and HeLa). In preliminary MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] cytotoxicity studies the optically active thiourea derivatives (IVe, IVf and IVh) were found most effective. In EAC cells the IC(50) values for IVe, IVf, IVh and Vg were found in the range of 10-24 microM, whereas in MCF-7 and HeLa cells the IC(50) values were observed in the range of 15-30 microM and 33-48 microM, respectively. In alkaline comet assay the compounds (IVe and IVf) showed dose-dependent DNA damaging activity.
Manjula
S N
SN
Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Madhav Nagar, Manipal, Karnataka, India.
Malleshappa Noolvi
N
N
Vipan Parihar
K
K
Manohara Reddy
S A
SA
Ramani
Vijay
V
Gadad
Andanappa K
AK
Singh
Gurdial
G
Gopalan Kutty
N
N
Mallikarjuna Rao
C
C
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D052160:Benzothiazoles / Q000737:chemistry*; D002286:Carcinoma, Ehrlich Tumor / Q000473:pathology; D045744:Cell Line, Tumor; D004249:DNA Damage / Q000187:drug effects; D015195:Drug Design; D006801:Humans; D051379:Mice; D055620:Optical Phenomena; D013890:Thiourea / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013997:Time Factors
D000970:Antineoplastic Agents; D052160:Benzothiazoles; C523775:aminobenzothiazole compound; D013890:Thiourea