Discovery of New Quinoxalines as Cytotoxic Agents: Design, Synthesis and Molecular Modeling

Ibrahim, Rabab Said; Ismail, Magda M.F.; Shawer, Taghreed Zakaria; Ammar, Yossry Ahmed

doi:10.21608/aijpms.2023.176667.1180

Discovery of New Quinoxalines as Cytotoxic Agents: Design, Synthesis and Molecular Modeling

Document Type : Original research articles

Authors

¹ Pharmaceutical Medicinal Chemistry department, Faculty of Pharmacy (Girls), Al-Azhar university

² professor, Department of Pharmaceutical Medicinal Chemistry and Drug Design, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, Egypt

³ Pharmaceutical medicinal chemistry and drug design department. Faculty of pharmacy (girls), Al Azhar University, Cairo, Egypt.

⁴ Department of Chemistry, Faculty of Science 11754 Al-Azhar University, Cairo, Egypt.

10.21608/aijpms.2023.176667.1180

Abstract

Vascular endothelial growth factor receptor-2 (VEGFR-2) has played a key role in cancer angiogenesis and vascular permeability. VEGFR-2 inhibitors proved effective suppression of tumor propagation; accordingly, a series of new 6-chloroquinoxaline derivatives has been designed and synthesized as VEGFR-2 inhibitors. The cytotoxic activities of the new compounds were tested against HCT-116 and MCF-7 cell lines. Remarkably, compound 6 elicited more cytotoxic activity against HCT-116 (IC50 6.18 μM) and MCF-7 (IC50 5.11μM) cell lines than doxorubicin (HCT-116 IC50 9.27 μM and MCF-7 IC50 7.43 μM) as reference drug. Moreover, compound 6 proved to be selective to cancer cells rather than human normal cell when examined against WI-38 cell lines. Molecular docking studies were implemented to interpret the binding mode of the target compounds in VEGFR-2 pocket. Furthermore, in silico results showed that, our compounds overcome sunitinib's drawbacks; they have no BBB permeation. Particularly, compounds 6 and 9 are not P-gp protein substrates as sunitinib.

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