Amidine- and Amidoxime-Substituted Heterocycles: Synthesis, Antiproliferative Evaluations and DNA Binding

Maračić, Silvija; Grbčić, Petra; Shammugam, Suresh; Radić Stojković, Marijana; Pavelić, Krešimir; Sedić, Mirela; Kraljević Pavelić, Sandra; Raić-Malić, Silvana (2021) Amidine- and Amidoxime-Substituted Heterocycles: Synthesis, Antiproliferative Evaluations and DNA Binding. Molecules, 26 (22). ISSN 1420-3049

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Official URL: https://www.mdpi.com/1420-3049/26/22/7060

Abstract

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.

Item Type:

Article

Uncontrolled Keywords:

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

Subjects:

NATURAL SCIENCES > Chemistry

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	Raić-Malić, Silvana	IP-2018-01-4682	HRZZ
Molekularno prepoznavanje DNA:RNA hibridnih i višelančanih struktura u bioanalitičkim i in vitro sustavima	Radić Stojković, Marijana	IP-2018-01-4694	HRZZ

Depositing User:

Marijana Radić Stojković

Date Deposited:

01 Feb 2022 14:09

URI:

http://fulir.irb.hr/id/eprint/6944

DOI:

10.3390/molecules26227060