Synthesis and Biological Activity of 2‐Benzo[b]thienyl and 2‐Bithienyl Amidino‐Substituted Benzothiazole and Benzimidazole Derivatives

Racané, Livio; Zlatić, Katarina; Cindrić, Maja; Mehić, Emina; Karminski‐Zamola, Grace; Taylor, Martin C.; Kelly, John M.; Raić Malić, Silvana; Stojković, Marijana Radić; Kralj, Marijeta; Hranjec, Marijana (2023) Synthesis and Biological Activity of 2‐Benzo[b]thienyl and 2‐Bithienyl Amidino‐Substituted Benzothiazole and Benzimidazole Derivatives. ChemMedChem, 18 (18). ISSN 1860-7179

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Abstract

Novel benzo[b]thienyl- and 2,2 & PRIME;-bithienyl-derived benzothiazoles and benzimidazoles were synthesized to study their antiproliferative and antitrypanosomal activities in vitro. Specifically, we assessed the impact that amidine group substitutions and the type of thiophene backbone have on biological activity. In general, the benzothiazole derivatives were more active than their benzimidazole analogs as both antiproliferative and antitrypanosomal agents. The 2,2 & PRIME;-bithienyl-substituted benzothiazoles with unsubstituted and 2-imidazolinyl amidine showed the most potent antitrypanosomal activity, and the greatest selectivity was observed for the benzimidazole derivatives bearing isopropyl, unsubstituted and 2-imidazolinyl amidine. The 2,2 & PRIME;-bithiophene derivatives showed most selective antiproliferative activity. Whereas the all 2,2 & PRIME;-bithienyl-substituted benzothiazoles were selectively active against lung carcinoma, the benzimidazoles were selective against cervical carcinoma cells. The compounds with an unsubstituted amidine group also produced strong antiproliferative effects. The more pronounced antiproliferative activity of the benzothiazole derivatives was attributed to different cytotoxicity mechanisms. Cell cycle analysis, and DNA binding experiments provide evidence that the benzimidazoles target DNA, whereas the benzothiazoles have a different cellular target because they are localized in the cytoplasm and do not interact with DNA.

Item Type:	Article
Uncontrolled Keywords:	amidines; antiproliferation; antiprotozoal agents; benzazoles; heterocycles
Subjects:	NATURAL SCIENCES > Chemistry NATURAL SCIENCES > Chemistry > Organic Chemistry BIOMEDICINE AND HEALTHCARE > Basic Medical Sciences
Divisions:	Division of Molecular Medicine Division of Organic Chemistry and Biochemistry
Projects:	Project title Project leader Project code Project type Istraživanje antioksidativnog djelovanja benzazolskog skeleta u dizajnu novih antitumorskih agensa-AntioxPot Marijana Hranjec; Livio Racane; Lucija Ptiček; Marijeta Kralj; Karmen Brajša; Ines Vujasinović; Kristina Butković; Ivana Novak Jovanović IP-2018-01-4379 HRZZ Molekularno prepoznavanje DNA:RNA hibridnih i višelančanih struktura u bioanalitičkim i in vitro sustavima-DNARNAHyB-MolBio Marijana Radić Stojković IP-2018-01-4694 HRZZ
Depositing User:	Josipa Karadžole
Date Deposited:	10 Jul 2026 12:10
URI:	https://fulir.irb.hr:/id/eprint/12041
DOI:	10.1002/cmdc.202300261

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