Synthesis, crystal structure and antiproliferative evaluation of some new substituted benzothiazoles and styrylbenzothiazoles

• Published in: Farmaco (Società chimica italiana : 1989) Vol. 59; no. 4; pp. 297 - 305
• Main Authors: Ćaleta, I., Grdiša, M., Mrvoš-Sermek, D., Cetina, M., Tralić-Kulenović, V., Pavelić, K., Karminski-Zamola, G.
• Format: Journal Article
• Language: English
• Published: France Elsevier SAS 01-04-2004
• Subjects: Amidinobenzothiazoles; Amidinostyrylbenzothiazoles; Antitumor activity; Benzothiazoles; Cell Division - drug effects; Cell Division - physiology; Cell Line; Cell Line, Tumor; Cell lines; Crystallization; Crystallography, X-Ray - methods; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical - methods; Fibroblasts - cytology; Fibroblasts - drug effects; Growth Inhibitors - chemical synthesis; Growth Inhibitors - chemistry; Growth Inhibitors - pharmacology; HeLa Cells; Humans; Thiazoles - chemical synthesis; Thiazoles - chemistry; Thiazoles - pharmacology; X-ray crystal structure analysis; Antitumor activity; Amidinostyrylbenzothiazoles; X-ray crystal structure analysis; Amidinobenzothiazoles; Cell lines
• ISSN: 0014-827X; 1879-0569
• DOI: 10.1016/j.farmac.2004.01.008

The multistep synthesis of a series of new substituted-benzothiazoles as hydrochloride or quaternary salts is described. 6-Amidino substituted 2-aminobenzothiazoles (
5,
6), N-methyl-2-(4-cyanostyryl)benzothiazolium iodide (
8), cyano-substituted-2-styrylbenzothiazoles (
9-11) and amidino and bis-amidino-substituted 2-styrylbenzothiazoles (
12-17) were prepared. The crystal structure of amidino derivative (
6) was determined by single crystal X-ray analysis. All new prepared compounds were tested on the cytostatic activities against malignant cell lines: (SW620, colon carcinoma; Hep2, laryngeal carcinoma; HBL, melanoma; HeLa, cervical carcinoma and WI38, human normal fibroblasts). The compounds exerted a different inhibitory effect, depended on concentration and type of the cells. The best inhibitory effect was achieved with compounds (
12-15), with slight differences among them. All of them inhibited the growth of examined tumor cell lines and also normal fibroblasts. Other examined compounds exhibited a moderate inhibitory effect, depending on type of the cells. Majority of them inhibited the growth of HeLa cells and WI38.