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Quinoline–imidazole/benzimidazole derivatives as dual-/multi-targeting hybrids inhibitors with anticancer and antimicrobial activity

Two new classes of hybrid quinoline–imidazole/benzimidazole derivatives (the hybrid QIBS salts and QIBC cycloadducts) were designed and synthesized to evaluate their anticancer and antimicrobial activity. The strategy adopted for synthesis is straight and efficient, in four steps: N-acylation, N-alk...

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Autores principales: Diaconu, Dumitrela, Antoci, Vasilichia, Mangalagiu, Violeta, Amariucai-Mantu, Dorina, Mangalagiu, Ionel I.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9551061/
https://www.ncbi.nlm.nih.gov/pubmed/36216981
http://dx.doi.org/10.1038/s41598-022-21435-6
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author Diaconu, Dumitrela
Antoci, Vasilichia
Mangalagiu, Violeta
Amariucai-Mantu, Dorina
Mangalagiu, Ionel I.
author_facet Diaconu, Dumitrela
Antoci, Vasilichia
Mangalagiu, Violeta
Amariucai-Mantu, Dorina
Mangalagiu, Ionel I.
author_sort Diaconu, Dumitrela
collection PubMed
description Two new classes of hybrid quinoline–imidazole/benzimidazole derivatives (the hybrid QIBS salts and QIBC cycloadducts) were designed and synthesized to evaluate their anticancer and antimicrobial activity. The strategy adopted for synthesis is straight and efficient, in four steps: N-acylation, N-alkylation, quaternization and a Huisgen 3 + 2 cycloaddition. The in vitro single-dose anticancer assay of forty six hybrid quinoline-benzimidazole compounds reveal that one QIBS salt (11h), has an excellent quasi nonselective activity against all type of cancer cell with an excellent PGI in the area of 90–100% and very good lethality. Three others quinoline–imidazole/benzimidazole hybrids (8h, 12h, 12f) has an excellent selective activity against some cancer cell lines: breast cancer MDA-MB-468 and Leukemia HL-60 TB). The five-dose assay screening confirms that compound 11h possesses excellent anti-proliferative activity, with GI(50) in the range of nano-molar, against some cancer cell lines: Leukemia HL-60 TB, Leukemia K-526, Leukemia RPMI-8226, Breast cancer MDA-MB-468, Lung cancer HOP-92 and Ovarian cancer IGROV1. The antibacterial assay indicates that three hybrid QIBS salts (12f, 12c, 12d) have an excellent activity against Gram-negative bacteria E. coli (superior to control Gentamicin) while against Gram-positive bacteria S. aureus only one compound 8i (R(2) = -CF3) exhibits a significant activity (superior to control Gentamicin). The MIC assay indicates that two other compounds (11h, 12h) are biologically active to a very low concentration, in the range of nano-molar. We believe that all these excellent assets related to anticancer and antibacterial activities, make from our hybrid quinoline–imidazole/benzimidazole compounds bearing a phenyl group (R(2) = –C(6)H(5)) in the para (4)-position of the benzoyl moiety a good candidate for future drug developing.
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spelling pubmed-95510612022-10-12 Quinoline–imidazole/benzimidazole derivatives as dual-/multi-targeting hybrids inhibitors with anticancer and antimicrobial activity Diaconu, Dumitrela Antoci, Vasilichia Mangalagiu, Violeta Amariucai-Mantu, Dorina Mangalagiu, Ionel I. Sci Rep Article Two new classes of hybrid quinoline–imidazole/benzimidazole derivatives (the hybrid QIBS salts and QIBC cycloadducts) were designed and synthesized to evaluate their anticancer and antimicrobial activity. The strategy adopted for synthesis is straight and efficient, in four steps: N-acylation, N-alkylation, quaternization and a Huisgen 3 + 2 cycloaddition. The in vitro single-dose anticancer assay of forty six hybrid quinoline-benzimidazole compounds reveal that one QIBS salt (11h), has an excellent quasi nonselective activity against all type of cancer cell with an excellent PGI in the area of 90–100% and very good lethality. Three others quinoline–imidazole/benzimidazole hybrids (8h, 12h, 12f) has an excellent selective activity against some cancer cell lines: breast cancer MDA-MB-468 and Leukemia HL-60 TB). The five-dose assay screening confirms that compound 11h possesses excellent anti-proliferative activity, with GI(50) in the range of nano-molar, against some cancer cell lines: Leukemia HL-60 TB, Leukemia K-526, Leukemia RPMI-8226, Breast cancer MDA-MB-468, Lung cancer HOP-92 and Ovarian cancer IGROV1. The antibacterial assay indicates that three hybrid QIBS salts (12f, 12c, 12d) have an excellent activity against Gram-negative bacteria E. coli (superior to control Gentamicin) while against Gram-positive bacteria S. aureus only one compound 8i (R(2) = -CF3) exhibits a significant activity (superior to control Gentamicin). The MIC assay indicates that two other compounds (11h, 12h) are biologically active to a very low concentration, in the range of nano-molar. We believe that all these excellent assets related to anticancer and antibacterial activities, make from our hybrid quinoline–imidazole/benzimidazole compounds bearing a phenyl group (R(2) = –C(6)H(5)) in the para (4)-position of the benzoyl moiety a good candidate for future drug developing. Nature Publishing Group UK 2022-10-10 /pmc/articles/PMC9551061/ /pubmed/36216981 http://dx.doi.org/10.1038/s41598-022-21435-6 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Diaconu, Dumitrela
Antoci, Vasilichia
Mangalagiu, Violeta
Amariucai-Mantu, Dorina
Mangalagiu, Ionel I.
Quinoline–imidazole/benzimidazole derivatives as dual-/multi-targeting hybrids inhibitors with anticancer and antimicrobial activity
title Quinoline–imidazole/benzimidazole derivatives as dual-/multi-targeting hybrids inhibitors with anticancer and antimicrobial activity
title_full Quinoline–imidazole/benzimidazole derivatives as dual-/multi-targeting hybrids inhibitors with anticancer and antimicrobial activity
title_fullStr Quinoline–imidazole/benzimidazole derivatives as dual-/multi-targeting hybrids inhibitors with anticancer and antimicrobial activity
title_full_unstemmed Quinoline–imidazole/benzimidazole derivatives as dual-/multi-targeting hybrids inhibitors with anticancer and antimicrobial activity
title_short Quinoline–imidazole/benzimidazole derivatives as dual-/multi-targeting hybrids inhibitors with anticancer and antimicrobial activity
title_sort quinoline–imidazole/benzimidazole derivatives as dual-/multi-targeting hybrids inhibitors with anticancer and antimicrobial activity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9551061/
https://www.ncbi.nlm.nih.gov/pubmed/36216981
http://dx.doi.org/10.1038/s41598-022-21435-6
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