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Exploration of novel VEGFR2 tyrosine kinase inhibitors via design and synthesis of new alkylated indolyl-triazole Schiff bases for targeting breast cancer by Mohamed S. Nafie; Ahmed T.A. Boraei is a Chemistry article available to read on EtoBox.

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According to the World Health Organization (WHO) statistics: In 2020, there were 2.3 million women diagnosed with breast cancer and 685,000 deaths globally. Therefore, searching for new leads for fighting this type of cancer is necessary. VEGFR-2 kinase plays a crucial role in the proliferation, migration, and survival of breast cancer cells so, identifying novel inhibitors for VEGFR-2 could be effective in breast cancer treatment. Accordingly, novel heterocyclic compounds containing indole, 1,2,4-triazole, and glycosyl or allyl moieties were synthesized. The synthesized compounds were evaluated for their cytotoxic and apoptotic activities towards breast cancer cell lines (MCF7). In this regard, compounds 6, 17, and 18 exhibited promising cytotoxic activity against MCF-7 cells with IC 50 values of 3.06, 1.18, and 3.02 μM compared to Sorafenib (IC 50 = 2.13 μM). Interestingly, among the identified lead molecules, compound 17 displayed remarkable VEGFR2 inhibition activity with IC 50 value of 19.8 nM compared to Sunitinib (IC 50 = 75 nM) and Sorafenib (IC 50 = 30 nM). Moreover, it is significantly stimulated apoptotic breast cancer cell death; it induced apoptosis by 17.4 %, arrestin

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Author

Mohamed S. Nafie; Ahmed T.A. Boraei

Publisher

Elsevier BV

Published

2022

Language

EN

Field

Chemistry (Physical Sciences)