Abstract

Abstract

In this study, a set of novel benzoxazole derivatives were designed, synthesised, and biologically evaluated as potential VEGFR-2 inhibitors. Five compounds (12d, 12f, 12i, 12l, and 13a) displayed high growth inhibitory activities against HepG2 and MCF-7 cell lines and were further investigated for their VEGFR-2 inhibitory activities. The most potent anti-proliferative member 12 l (IC50 = 10.50 μM and 15.21 μM against HepG2 and MCF-7, respectively) had the most promising VEGFR-2 inhibitory activity (IC50 = 97.38 nM). A further biological evaluation revealed that compound 12l could arrest the HepG2 cell growth mainly at the Pre-G1 and G1 phases. Furthermore, compound 12l could induce apoptosis in HepG2 cells by 35.13%. likely, compound 12l exhibited a significant elevation in caspase-3 level (2.98-fold) and BAX (3.40-fold), and a significant reduction in Bcl-2 level (2.12-fold). Finally, docking studies indicated that 12l exhibited interactions with the key amino acids in a similar way to sorafenib.

Details

Title
Benzoxazole derivatives as new VEGFR-2 inhibitors and apoptosis inducers: design, synthesis, in silico studies, and antiproliferative evaluation
Author
Taghour, Mohammed S 1 ; Mahdy, Hazem A 1 ; Gomaa, Maher H 2 ; Aglan, Ahmed 2 ; Mahmoud Gomaa Eldeib 2 ; Elwan, Alaa 1 ; Dahab, Mohammed A 1 ; Elkaeed, Eslam B 3 ; Alsfouk, Aisha A 4 ; Khalifa, Mohamed M 1 ; Eissa, Ibrahim H 1 ; Elkady, Hazem 1 

1  Pharmaceutical Medicinal Chemistry & Drug Design Department, Faculty of Pharmacy (Boys), Al-Azhar University , Cairo , Egypt 
2  Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University , Cairo , Egypt 
3  Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy (Boys), Al-Azhar University , Cairo , Egypt 
4  Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah bint Abdulrahman University , Riyadh , Saudi Arabia 
Pages
2063-2077
Publication year
2022
Publication date
Dec 2022
Publisher
Taylor & Francis Ltd.
ISSN
14756366
e-ISSN
14756374
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1080/14756366.2022.2103552
ProQuest document ID
2727916008
Copyright
© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.. This work is licensed under the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/ (the "License"). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.