Synthesis and cytotoxic evaluation of thiourea and N-bis-benzothiazole derivatives: A novel class of cytotoxic agents

• Published in: Bioorganic & medicinal chemistry letters Vol. 22; no. 1; pp. 453 - 455
• Main Authors: Kumbhare, Ravindra M., Dadmal, Tulshiram, Kosurkar, Umesh, Sridhar, V., Rao, J. Venkateswara
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 01.01.2012; Elsevier
• Subjects: 1,3-Di-n-butylimidazolium tribromide[bbim][Br3]; Animals; Antineoplastic Agents - pharmacology; Benzothiazoles - chemical synthesis; Benzothiazoles - chemistry; Benzothiazolyl thiocarbamide; Biological and medical sciences; Catalysis; Cell Line, Tumor; chemistry; Chemistry, Pharmaceutical - methods; Chemoselective oxidative cyclization; Cytotoxic activity; cytotoxicity; Drug Design; Humans; Inhibitory Concentration 50; Medical sciences; melanoma; Melanoma, Experimental - metabolism; Mice; Models, Chemical; Molecular Structure; N-Bis-benzothiazole; Pharmacology. Drug treatments; thiourea; Thiourea - chemistry; U937 Cells; Benzothiazolyl thiocarbamide; Chemoselective oxidative cyclization; N-Bis-benzothiazole; 1,3-Di-n-butylimidazolium tribromide[bbim][Br3]; Cytotoxic activity; Antineoplastic agent; Evaluation; Organic cation; Chemoselectivity; Cytotoxicity; Metabolism; Benzothiazole derivatives; Thioureas; Biological activity; 1,3-Di-n-butylimidazolium; Cyclization; tribromide[bbim][Br; Oxidation; Pharmacokinetics; Chemical synthesis; ]
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2011.10.106

Benzothiazolyl thiocarbamides has been achieved using a catalytic amount of 4-dimethylaminopyridine (DMAP) followed by its chemoselective oxidative cyclization with 1,3-di-n-butylimidazolium tribromide[bbim][Br3] to afford the N-bis-benzothiazole derivatives. All the synthesized compounds were evaluated for cytotoxic activity against two human monocytic cell lines (U 937, THP-1) and a mouse melanoma cell line (B16-F10). Based on their IC50 values, the majority of the benzothiazolyl thiocarbamides and N-bis-benzothiazoles had significant antiproliferative activity on U 937 and B16-F10 cells, the compounds 3b, 3e, 3f, 3k, 6c and 6h were found to be the most active. The present findings indicate clearly that the compound 3e exhibited more antiproliferative activity on U 937 cells than the standard molecule, etoposide. Nevertheless, these compounds have shown comparatively less cytotoxicity towards THP-1 cells.