Naslov
Amidine- and amidoxime-substituted heterocycles: Synthesis, antiproliferative evaluations and DNA binding

Autori
Maračić, Silvija ; Grbčić, Petra ; Shanmugam, Suresh ; Radić Stojković, Marijana ; Pavelić, Krešimir ; Sedić, Mirela ; Kraljević Pavelić, Sandra ; Raić-Malić, Silvana

Izvornik
Molecules (1420-3049) 26 (2021), 22; 7060, 22

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

Ključne riječi
amidine ; amidoxime ; antiproliferative activity ; DNA binding ; fluorescence ; CD spec-troscopy ; thermal denaturation

Sažetak
The novel 1, 2, 3-triazolyl-appended N- and O- heterocycles containing amidine 4–11 andamidoxime 12–22 moiety were prepared and evaluated for their antiproliferative activitiesin vitro. Among the series of amidine-substituted heterocycles, aromatic diamidine 5 and coumarine amidine 11 had the most potent growth-inhibitory effect on cervical carcinoma (HeLa), hepatocellular carci- noma (HepG2) and colorectal adenocarcinoma (SW620), with IC50 values in the nM range. Although compound 5 was toxic to non-tumor HFF cells, compound 11 showed certain selectivity. From the amidoxime series, quinoline amidoximes 18 and 20 showed antiproliferative effects on lung adeno-carcinoma (A549), HeLa and SW620 cells emphasizing compound 20 that exhibited no cytostatic effect on normal HFF fibroblasts. Results of CD titrations and thermal melting experiments indicated that compounds 5 and 10 most likely bind inside the minor groove of AT-DNA and intercalate into AU-RNA. Compounds 6, 9 and 11 bind to AT-DNA with mixed binding mode, most probably minor groove binding accompanied with aggregate binding along the DNA backbone.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

POVEZANOST RADA