Synthesis, antiproliferative and antitrypanosomal activities, and DNA binding of novel 6-amidino-2-arylbenzothiazoles

Racané, Livio; Rep, Valentina; Kraljević Pavelić, Sandra; Grbčić, Petra; Zonjić, Iva; Radić Stojković, Marijana; Taylor, Martin C.; Kelly, John M.; Raić-Malić, Silvana (2021) Synthesis, antiproliferative and antitrypanosomal activities, and DNA binding of novel 6-amidino-2-arylbenzothiazoles. Journal of Enzyme Inhibition and Medicinal Chemistry, 36 (1). pp. 1952-1967. ISSN 1475-6366

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Abstract

A series of 6-amidinobenzothiazoles, linked via phenoxymethylene or directly to the 1,2,3-triazole ring with a p-substituted phenyl or benzyl moiety, were synthesised and evaluated in vitro against four human tumour cell lines and the protozoan parasite Trypanosoma brucei. The influence of the type of amidino substituent and phenoxymethylene linker on antiproliferative and antitrypanosomal activities was observed, showing that the imidazoline moiety had a major impact on both activities. Benzothiazole imidazoline 14a, which was directly connected to N-1-phenyl-1,2,3-triazole, had the most potent growth-inhibitory effect (IC50 = 0.25 µM) on colorectal adenocarcinoma (SW620), while benzothiazole imidazoline 11b, containing a phenoxymethylene linker, exhibited the best antitrypanosomal potency (IC90 = 0.12 µM). DNA binding assays showed a non-covalent interaction of 6-amidinobenzothiazole ligands, indicating both minor groove binding and intercalation modes of DNA interaction. Our findings encourage further development of novel structurally related 6-amidino-2-arylbenzothiazoles to obtain more selective anticancer and anti-HAT agents.

Item Type:	Article
Uncontrolled Keywords:	Benzothiazole; amidine; antiproliferative activity; Trypanosoma brucei; ctDNA binding
Subjects:	NATURAL SCIENCES > Chemistry NATURAL SCIENCES > Biology > Biochemistry and Molecular Biology
Divisions:	Division of Organic Chemistry and Biochemistry
Projects:	Project title Project leader Project code Project type Novi spojevi temeljeni na bioizosterima purina za ispitivanje njihovih antitumorskih i antipatogenih djelovanja-PurBioCaPa Silvana Raić-Malić; Krešimir Pavelić; Anja Harej; Domagoj Drenjančević; John M. Kelly; Andrea Bistrović; Sanja Koštrun IP-2018-01-4682 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:	Ana Zečević
Date Deposited:	27 Mar 2024 11:23
URI:	http://fulir.irb.hr/id/eprint/8744
DOI:	10.1080/14756366.2021.1959572

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