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Design, Synthesis and Cytotoxic Activity of Novel Salicylaldehyde Hydrazones against Leukemia and Breast Cancer

Despite the significant advancements in complex anticancer therapy, the search for new and more efficient specific anticancer agents remains a top priority in the field of drug discovery and development. Here, based on the structure-activity relationships (SARs) of eleven salicylaldehyde hydrazones...

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Autores principales: Nikolova-Mladenova, Boryana, Momekov, Georgi, Zhivkova, Zvetanka, Doytchinova, Irini
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10138506/
https://www.ncbi.nlm.nih.gov/pubmed/37108514
http://dx.doi.org/10.3390/ijms24087352
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author Nikolova-Mladenova, Boryana
Momekov, Georgi
Zhivkova, Zvetanka
Doytchinova, Irini
author_facet Nikolova-Mladenova, Boryana
Momekov, Georgi
Zhivkova, Zvetanka
Doytchinova, Irini
author_sort Nikolova-Mladenova, Boryana
collection PubMed
description Despite the significant advancements in complex anticancer therapy, the search for new and more efficient specific anticancer agents remains a top priority in the field of drug discovery and development. Here, based on the structure-activity relationships (SARs) of eleven salicylaldehyde hydrazones with anticancer activities, we designed three novel derivatives. The compounds were tested in silico for drug-likeness, synthesized, and evaluated in vitro for anticancer activity and selectivity on four leukemic cell lines (HL-60, KE-37, K-562, and BV-173), one osteosarcomic cell line (SaOS-2), two breast adenocarcinomic cell lines (MCF-7 and MDA-MB-231), and one healthy cell line (HEK-293). The designed compounds were found to have appropriate drug likeness and showed anticancer activities in all cell lines tested; particularly, two of them exhibited remarkable anticancer activity in nanomolar concentrations on the leukemic cell lines HL-60 and K-562 and the breast cancer MCF-7 cells and extraordinary selectivity for the same cancer lines ranging between 164- and 1254-fold. The study also examined the effects of different substituents on the hydrazone scaffold and found that the 4-methoxy salicylic moiety, phenyl, and pyridinyl rings are the most appropriate for anticancer activity and selectivity of this chemical class.
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spelling pubmed-101385062023-04-28 Design, Synthesis and Cytotoxic Activity of Novel Salicylaldehyde Hydrazones against Leukemia and Breast Cancer Nikolova-Mladenova, Boryana Momekov, Georgi Zhivkova, Zvetanka Doytchinova, Irini Int J Mol Sci Article Despite the significant advancements in complex anticancer therapy, the search for new and more efficient specific anticancer agents remains a top priority in the field of drug discovery and development. Here, based on the structure-activity relationships (SARs) of eleven salicylaldehyde hydrazones with anticancer activities, we designed three novel derivatives. The compounds were tested in silico for drug-likeness, synthesized, and evaluated in vitro for anticancer activity and selectivity on four leukemic cell lines (HL-60, KE-37, K-562, and BV-173), one osteosarcomic cell line (SaOS-2), two breast adenocarcinomic cell lines (MCF-7 and MDA-MB-231), and one healthy cell line (HEK-293). The designed compounds were found to have appropriate drug likeness and showed anticancer activities in all cell lines tested; particularly, two of them exhibited remarkable anticancer activity in nanomolar concentrations on the leukemic cell lines HL-60 and K-562 and the breast cancer MCF-7 cells and extraordinary selectivity for the same cancer lines ranging between 164- and 1254-fold. The study also examined the effects of different substituents on the hydrazone scaffold and found that the 4-methoxy salicylic moiety, phenyl, and pyridinyl rings are the most appropriate for anticancer activity and selectivity of this chemical class. MDPI 2023-04-16 /pmc/articles/PMC10138506/ /pubmed/37108514 http://dx.doi.org/10.3390/ijms24087352 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Nikolova-Mladenova, Boryana
Momekov, Georgi
Zhivkova, Zvetanka
Doytchinova, Irini
Design, Synthesis and Cytotoxic Activity of Novel Salicylaldehyde Hydrazones against Leukemia and Breast Cancer
title Design, Synthesis and Cytotoxic Activity of Novel Salicylaldehyde Hydrazones against Leukemia and Breast Cancer
title_full Design, Synthesis and Cytotoxic Activity of Novel Salicylaldehyde Hydrazones against Leukemia and Breast Cancer
title_fullStr Design, Synthesis and Cytotoxic Activity of Novel Salicylaldehyde Hydrazones against Leukemia and Breast Cancer
title_full_unstemmed Design, Synthesis and Cytotoxic Activity of Novel Salicylaldehyde Hydrazones against Leukemia and Breast Cancer
title_short Design, Synthesis and Cytotoxic Activity of Novel Salicylaldehyde Hydrazones against Leukemia and Breast Cancer
title_sort design, synthesis and cytotoxic activity of novel salicylaldehyde hydrazones against leukemia and breast cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10138506/
https://www.ncbi.nlm.nih.gov/pubmed/37108514
http://dx.doi.org/10.3390/ijms24087352
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