Synthesis and Biological Evaluation of Novel Amino and Amido Substituted Pentacyclic Benzimidazole Derivatives as Antiproliferative Agents

Perin, Nataša; Gulin, Marjana; Kos, Marija; Persoons, Leentje; Daelemans, Dirk; Fabijanić, Ivana; Stojković, Marijana Radić; Hranjec, Marijana (2024) Synthesis and Biological Evaluation of Novel Amino and Amido Substituted Pentacyclic Benzimidazole Derivatives as Antiproliferative Agents. International Journal of Molecular Sciences, 25 (4). ISSN 1422-0067

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Abstract

Newly designed pentacyclic benzimidazole derivatives featuring amino or amido side chains were synthesized to assess their in vitro antiproliferative activity. Additionally, we investigated their direct interaction with nucleic acids, aiming to uncover potential mechanisms of biological action. These compounds were prepared using conventional organic synthesis methodologies alongside photochemical and microwave-assisted reactions. Upon synthesis, the newly derived compounds underwent in vitro testing for their antiproliferative effects on various human cancer cell lines. Notably, derivatives 6 and 9 exhibited significant antiproliferative activity within the submicromolar concentration range. The biological activity was strongly influenced by the N atom's position on the quinoline moiety and the position and nature of the side chain on the pentacyclic skeleton. Findings from fluorescence, circular dichroism spectroscopy, and thermal melting assays pointed toward a mixed binding mode-comprising intercalation and the binding of aggregated compounds along the polynucleotide backbone-of these pentacyclic benzimidazoles with DNA and RNA.

Item Type:	Article
Uncontrolled Keywords:	antiproliferative activity; amines; amides; benzimidazoles; interaction with DNA
Subjects:	NATURAL SCIENCES NATURAL SCIENCES > Chemistry > Organic Chemistry NATURAL SCIENCES > Biology > Biochemistry and Molecular Biology
Divisions:	Division of Organic Chemistry and Biochemistry
Projects:	Project title Project leader Project code Project type Istraživanje antioksidativnog djelovanja benzazolskog skeleta u dizajnu novih antitumorskih agensa-AntioxPot Marijana Hranjec IP-2018-01-4379 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:	Diana Mikoč Radešić
Date Deposited:	13 Aug 2024 12:56
URI:	http://fulir.irb.hr/id/eprint/9009
DOI:	10.3390/ijms25042288

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