Synthesis and antitumor activity of optically active thiourea and their 2-aminobenzothiazole derivatives: A novel class of anticancer agents

• Published in: European journal of medicinal chemistry Vol. 44; no. 7; pp. 2923 - 2929
• Main Authors: Manjula, S.N., Malleshappa Noolvi, N., Vipan Parihar, K., Manohara Reddy, S.A., Ramani, Vijay, Gadad, Andanappa K., Singh, Gurdial, Gopalan Kutty, N., Mallikarjuna Rao, C.
• Format: Journal Article
• Language: English
• Published: ISSY-LES-MOULINEAUX Elsevier Masson SAS 01.07.2009; Elsevier
• Subjects: 2-Aminobenzothiazoles; Animals; Antineoplastic agents; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Benzothiazoles - chemistry; Biological and medical sciences; Carcinoma, Ehrlich Tumor - pathology; Cell Line, Tumor; Chemistry, Medicinal; Comet assay; DNA damage; DNA Damage - drug effects; Drug Design; General aspects; Humans; Life Sciences & Biomedicine; MCF-7; Medical sciences; Mice; MTT assay; Optical Phenomena; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Science & Technology; Thiourea; Thiourea - chemical synthesis; Thiourea - chemistry; Thiourea - pharmacology; Time Factors; Thiourea; 2-Aminobenzothiazoles; MTT assay; DNA damage; MCF-7; Comet assay; APOPTOSIS; CELLS; DNA-DAMAGE; INHIBITORY-ACTIVITY; POTENT; BIOLOGICAL EVALUATION; BENZOTHIAZOLES; Antineoplastic agent; Cytotoxicity; Uterine cervix; Thioureas; Structure activity relation; Enantiomer; Bicyclic compound; Cleavage; Aromatic compound; Mammary gland; Mechanism of action; Chemical synthesis; Tumor cell; Human; Sulfur nitrogen heterocycle; Mutagenicity testing; Rodentia; Benzothiazole derivatives; In vitro; Hela cell line; Vertebrata; Mammalia; Cell line; Mouse; DNA; Lesion
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2008.12.002

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, 1H NMR, 13C 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 μM, whereas in MCF-7 and HeLa cells the IC 50 values were observed in the range of 15–30 μM and 33–48 μM, respectively. In alkaline comet assay the compounds ( IVe and IVf) showed dose-dependent DNA damaging activity. [Display omitted] A series of novel optically active thiourea and their 2-aminobenzothiazole derivatives had been synthesised and evaluated for in vitro cytotoxicity against EAC, MCF-7, HeLa cells.