Synthesis, antiproliferative and antitrypanosomal activities, and DNA binding of novel 6-amidino-2-arylbenzothiazoles. (1st January 2021)

• Record Type: Journal Article
• Authors: Racané, Livio; Rep, Valentina; Kraljević Pavelić, Sandra; Grbčić, Petra; Zonjić, Iva; Radić Stojković, Marijana; Taylor, Martin C.; Kelly, John M.; Raić-Malić, Silvana
• Is Part Of: Journal of enzyme inhibition and medicinal chemistry. Volume 36:Number 1(2021)
• Page Start: 1952
• Page End: 1967
• Publication Date: 2021-01-01
• Subjects: Benzothiazole -- amidine -- antiproliferative activity -- Trypanosoma brucei -- ctDNA binding; Enzyme inhibitors -- Periodicals; Enzyme Inhibitors -- periodicals; Biochemistry -- periodicals; 572.7
• DOI: 10.1080/14756366.2021.1959572
• Languages: English
• ISSNs: 1475-6366

Abstract

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. Graphical Abstract: UF0001