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

Autori
Racané, Livio ; Rep, Valentina ; Kraljević Pavelić, Sandra ; Grbčić, Petra ; Zonjić, Iva ; Radić Stojković, Marijana ; Taylor, Martin C. ; Kelly, John M. ; Raić-Malić, Silvana

Izvornik
Journal of enzyme inhibition and medicinal chemistry (1475-6366) 36 (2021), 1; 1952-1967

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
benzothiazole ; amidine ; antiproliferative activity ; Trypanosoma brucei ; ctDNA binding

Sažetak
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.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

POVEZANOST RADA