Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

Nataša Perin
,
Marjana Gulin
,
Marjana Gulin
,
Leentje Persoons
ORCID logo ,
Dirk Daelmans
ORCID logo ,
Ivana Fabijanić
,
Marijana Radić Stojković
* ,
Marijana Hranjec
*
Version 1 : Received: 12 January 2024 / Approved: 12 January 2024 / Online: 12 January 2024 (15:11:23 CET)

A peer-reviewed article of this Preprint also exists.

Perin, N.; Gulin, M.; Kos, M.; Persoons, L.; Daelemans, D.; Fabijanić, I.; Stojković, M.R.; Hranjec, M. Synthesis and Biological Evaluation of Novel Amino and Amido Substituted Pentacyclic Benzimidazole Derivatives as Antiproliferative Agents. Int. J. Mol. Sci. 2024, 25, 2288. Perin, N.; Gulin, M.; Kos, M.; Persoons, L.; Daelemans, D.; Fabijanić, I.; Stojković, M.R.; Hranjec, M. Synthesis and Biological Evaluation of Novel Amino and Amido Substituted Pentacyclic Benzimidazole Derivatives as Antiproliferative Agents. Int. J. Mol. Sci. 2024, 25, 2288.

Abstract

Newly designed pentacyclic benzimidazole derivatives, featuring amino or amido side chains, were synthesized to assess their in vitro antiproliferative activity. Additionally, we conducted investigations into their direct interaction with nucleic acids, aiming to uncover potential mechanisms of biological action. These compounds were synthesized 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. Our biological assessment highlighted that the biological activity was strongly influenced by both the position of the N atom 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 indicated a mixed binding mode—comprising intercalation and the binding of aggregated compounds along the polynucleotide backbone—of these pentacyclic benzimidazoles with DNA and RNA.

Keywords

antiproliferative activity; amines; amides; benzimidazoles; interaction with DNA

Subject

Biology and Life Sciences, Life Sciences

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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