Coumarin-acetohydrazide derivatives as novel antiproliferative agents via VEGFR-2/AKT axis inhibition and apoptosis triggering

Lina M. A. Abdel Ghany; Nehad M. El-Dydamony; Amira A. Helwa; Sahar M. Abdelraouf; Rana M. Abdelnaby

doi:10.1039/D2NJ02436E

Coumarin-acetohydrazide derivatives as novel antiproliferative agents via VEGFR-2/AKT axis inhibition and apoptosis triggering†

Lina M. A. Abdel Ghany,^a Nehad M. El-Dydamony,^a Amira A. Helwa,

*^b Sahar M. Abdelraouf^c and Rana M. Abdelnaby

Author affiliations

* Corresponding authors

^a Pharmaceutical Chemistry Department, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology, 6th of October City, Egypt

^b Pharmaceutical Organic Chemistry Department, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology, 6th of October City, Egypt
E-mail: Amira.helwa@must.edu.eg
Tel: +20-01006901734

^c Biochemistry Department, Faculty of pharmacy, Misr International University, Cairo, Egypt

^d Pharmaceutical Chemistry Department, Faculty of Pharmacy, Heliopolis University, Cairo, Egypt

Abstract

The VEGFR-2/AKT pathway is a crucial axis in tumor survival where it is highly dysregulated in many cancer types. In this research, novel coumarin-acid hydrazides were synthesized and assayed for their anticancer activity in MCF-7 and Panc-1 cells via MTT assay where most compounds especially 4f and 4k showed promising antiproliferative activity with an IC₅₀ of 0.73, 1.19 and 0.84, 3.61 μM against both cell lines, respectively. Their inhibitory activity on VEGFR-2/AKT-1 proteins was very promising with IC₅₀ values of 0.18 and 0.12 μM on VEGFR-2 and 5.7 and 8.1 μM on AKT by 4f and 4k, respectively. Also, flow cytometry revealed cell cycle arrest with elevated caspase 8 and 9 levels leading to apoptosis by both compounds. Furthermore, docking studies revealed binding patterns similar to the reference ligands in VEGFR-2 and AKT-1 binding sites. Thus, these novel coumarin derivatives are promising anticancer leads via inhibiting the VEGFR-2/AKT axis and apoptosis induction.

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DOI: https://doi.org/10.1039/D2NJ02436E
Article type: Paper
Submitted: 17 May 2022
Accepted: 15 Aug 2022
First published: 17 Aug 2022

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New J. Chem., 2022,46, 17394-17409

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Coumarin-acetohydrazide derivatives as novel antiproliferative agents via VEGFR-2/AKT axis inhibition and apoptosis triggering

L. M. A. Abdel Ghany, N. M. El-Dydamony, A. A. Helwa, S. M. Abdelraouf and R. M. Abdelnaby, New J. Chem., 2022, 46, 17394 DOI: 10.1039/D2NJ02436E

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New Journal of Chemistry

Coumarin-acetohydrazide derivatives as novel antiproliferative agents via VEGFR-2/AKT axis inhibition and apoptosis triggering†

Abstract

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Coumarin-acetohydrazide derivatives as novel antiproliferative agents via VEGFR-2/AKT axis inhibition and apoptosis triggering

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