Salicylaldehyde Benzoylhydrazones with Anticancer Activity and Selectivity: Design, Synthesis, and In Vitro Evaluation

Dimethoxy derivatives of salicylaldehyde benzoylhydrazone containing a methoxy group on both aromatic rings were designed and synthesized. The compounds were obtained in high yields, and their structures were confirmed by elemental analysis and various spectral techniques. In vitro evaluation of dim...

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Main Authors: Boryana Nikolova-Mladenova, Rositsa Mihaylova, Mariyana Atanasova, Zvetanka Zhivkova, Irini Doytchinova
Format: Article
Language:English
Published: MDPI AG 2025-02-01
Series:Molecules
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Online Access:https://www.mdpi.com/1420-3049/30/5/1015
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author Boryana Nikolova-Mladenova
Rositsa Mihaylova
Mariyana Atanasova
Zvetanka Zhivkova
Irini Doytchinova
author_facet Boryana Nikolova-Mladenova
Rositsa Mihaylova
Mariyana Atanasova
Zvetanka Zhivkova
Irini Doytchinova
author_sort Boryana Nikolova-Mladenova
collection DOAJ
description Dimethoxy derivatives of salicylaldehyde benzoylhydrazone containing a methoxy group on both aromatic rings were designed and synthesized. The compounds were obtained in high yields, and their structures were confirmed by elemental analysis and various spectral techniques. In vitro evaluation of dimethoxy hydrazones demonstrated potent activity against the leukemic cell lines at low micro- and nanomolar concentrations. Remarkably, two dimethoxy analogs showed exceptional antileukemic selectivity, with no toxicity observed in normal human embryonic kidney HEK-293 cells. In silico modeling identified likely interactions with the target, human cAbl kinase, and suggested a possible mechanism for their antileukemic activity.
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id doaj-art-d22ba18e2f124825855eca5a7583e25d
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issn 1420-3049
language English
publishDate 2025-02-01
publisher MDPI AG
record_format Article
series Molecules
spelling doaj-art-d22ba18e2f124825855eca5a7583e25d2025-08-20T02:53:22ZengMDPI AGMolecules1420-30492025-02-01305101510.3390/molecules30051015Salicylaldehyde Benzoylhydrazones with Anticancer Activity and Selectivity: Design, Synthesis, and In Vitro EvaluationBoryana Nikolova-Mladenova0Rositsa Mihaylova1Mariyana Atanasova2Zvetanka Zhivkova3Irini Doytchinova4Department of Chemistry, Faculty of Pharmacy, Medical University of Sofia, 2 Dunav Str., 1000 Sofia, BulgariaDepartment of Pharmacology, Pharmacotherapy and Toxicology, Faculty of Pharmacy, Medical University of Sofia, 2 Dunav Str., 1000 Sofia, BulgariaDepartment of Chemistry, Faculty of Pharmacy, Medical University of Sofia, 2 Dunav Str., 1000 Sofia, BulgariaDepartment of Chemistry, Faculty of Pharmacy, Medical University of Sofia, 2 Dunav Str., 1000 Sofia, BulgariaDepartment of Chemistry, Faculty of Pharmacy, Medical University of Sofia, 2 Dunav Str., 1000 Sofia, BulgariaDimethoxy derivatives of salicylaldehyde benzoylhydrazone containing a methoxy group on both aromatic rings were designed and synthesized. The compounds were obtained in high yields, and their structures were confirmed by elemental analysis and various spectral techniques. In vitro evaluation of dimethoxy hydrazones demonstrated potent activity against the leukemic cell lines at low micro- and nanomolar concentrations. Remarkably, two dimethoxy analogs showed exceptional antileukemic selectivity, with no toxicity observed in normal human embryonic kidney HEK-293 cells. In silico modeling identified likely interactions with the target, human cAbl kinase, and suggested a possible mechanism for their antileukemic activity.https://www.mdpi.com/1420-3049/30/5/1015salicylaldehydehydrazonesmethoxy groupantileukemic activityselectivity
spellingShingle Boryana Nikolova-Mladenova
Rositsa Mihaylova
Mariyana Atanasova
Zvetanka Zhivkova
Irini Doytchinova
Salicylaldehyde Benzoylhydrazones with Anticancer Activity and Selectivity: Design, Synthesis, and In Vitro Evaluation
Molecules
salicylaldehyde
hydrazones
methoxy group
antileukemic activity
selectivity
title Salicylaldehyde Benzoylhydrazones with Anticancer Activity and Selectivity: Design, Synthesis, and In Vitro Evaluation
title_full Salicylaldehyde Benzoylhydrazones with Anticancer Activity and Selectivity: Design, Synthesis, and In Vitro Evaluation
title_fullStr Salicylaldehyde Benzoylhydrazones with Anticancer Activity and Selectivity: Design, Synthesis, and In Vitro Evaluation
title_full_unstemmed Salicylaldehyde Benzoylhydrazones with Anticancer Activity and Selectivity: Design, Synthesis, and In Vitro Evaluation
title_short Salicylaldehyde Benzoylhydrazones with Anticancer Activity and Selectivity: Design, Synthesis, and In Vitro Evaluation
title_sort salicylaldehyde benzoylhydrazones with anticancer activity and selectivity design synthesis and in vitro evaluation
topic salicylaldehyde
hydrazones
methoxy group
antileukemic activity
selectivity
url https://www.mdpi.com/1420-3049/30/5/1015
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AT rositsamihaylova salicylaldehydebenzoylhydrazoneswithanticanceractivityandselectivitydesignsynthesisandinvitroevaluation
AT mariyanaatanasova salicylaldehydebenzoylhydrazoneswithanticanceractivityandselectivitydesignsynthesisandinvitroevaluation
AT zvetankazhivkova salicylaldehydebenzoylhydrazoneswithanticanceractivityandselectivitydesignsynthesisandinvitroevaluation
AT irinidoytchinova salicylaldehydebenzoylhydrazoneswithanticanceractivityandselectivitydesignsynthesisandinvitroevaluation