SYNTHESIS AND ANTITUMOR ACTIVITY OF NOVEL 2-THIOXO-4-THIAZOLIDINONES WITH BENZOTHIAZOLE MOIETIES

Abstract

Following the reaction of benzothiazol-2-yl-hydrazine or (2-oxo-benzothiazol-3yl)-acetic acid hydrazide with thiocarbonyl-bis-thioglycolic acid, 3-(benzothiazol-2ylamino)-2-thioxothiazolidin-4-one (1) and 2-(2-oxobenzothiazol-3-yl)-N-(4-oxo-2thioxothiazolidin-3-yl)-acetamide (2) were synthesized, as starting compounds for obtaining new 5-arylidenederivatives (3-6) in Knoevenagel condensation with aromatic aldehydes and isatines. The synthesized compounds showed antitumor activity on renal cancer, non-small cell lung cancer and ovarian cancer cell lines. The most efficient anticancer agent, 2-{2-[3-(benzothiazol-2-ylamino)-4-oxo-2-thioxo-thiazolidin-5ylidenemethyl]-4-chloro-phenoxy}-N-(4-methoxyphenyl)-acetamide 3d was found to be active with average values of -5.38 and -4.45 for logGI50 and logTGI, respectively. Rezumat Prin reacţia de condensare intre acidul tiocarbonil-bis-tioglicolic cu benzotiazol-2il-hidrazina sau cu hidrazida acidului 2-oxo-benzotiazol-3-il-acetic, s-au obţinut 3(benzotiazol-2-il-amino)-2-tioxo-tiazolidin-4-ona (1) si 2-(2-oxobenzotiazol-3-il)-N-(4-oxo-2tioxotiazolidin-3-il)-acetamida (2), intermediari necesari sintezei unor noi 5-ariliden-derivaţi (3-6), printr-o reacţie de condensare Knoevenagel cu aldehide aromatice si isatine. Compusii sintetizaţi prezinta activitate antitumorala asupra unor linii celulare canceroase renale, pulmonare si ovariene. Cel mai eficient efect anticanceros a fost evidenţiat la compusul 2-{2[3-(benzotiazol-2-il-amino)-4-oxo-2-tioxo-tiazolidin-5-ilidenemetil]-4-cloro-fenoxi}-N-(4metoxifenil)-acetamida (3d) ce prezinta valori de -5,38, respectiv de -4,45 pentru log GI50 si log TGI.