Discovery of New Quinoxalines as Cytotoxic Agents: Design, Synthesis and Molecular Modeling
Ibrahim, R., Ismail, M., Shawer, T., Ammar, Y. (2023). Discovery of New Quinoxalines as Cytotoxic Agents: Design, Synthesis and Molecular Modeling. EKB Journal Management System, 3(2), 119-132. doi: 10.21608/aijpms.2023.176667.1180
Rabab Said Ibrahim; Magda M.F. Ismail; Taghreed Zakaria Shawer; Yossry Ahmed Ammar. "Discovery of New Quinoxalines as Cytotoxic Agents: Design, Synthesis and Molecular Modeling". EKB Journal Management System, 3, 2, 2023, 119-132. doi: 10.21608/aijpms.2023.176667.1180
Ibrahim, R., Ismail, M., Shawer, T., Ammar, Y. (2023). 'Discovery of New Quinoxalines as Cytotoxic Agents: Design, Synthesis and Molecular Modeling', EKB Journal Management System, 3(2), pp. 119-132. doi: 10.21608/aijpms.2023.176667.1180
Ibrahim, R., Ismail, M., Shawer, T., Ammar, Y. Discovery of New Quinoxalines as Cytotoxic Agents: Design, Synthesis and Molecular Modeling. EKB Journal Management System, 2023; 3(2): 119-132. doi: 10.21608/aijpms.2023.176667.1180

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

Azhar International Journal of Pharmaceutical and Medical Sciences
Volume 3, Issue 2, June 2023, Page 119-132  XML PDF (817.13 K)
Document Type: Original research articles
DOI: 10.21608/aijpms.2023.176667.1180
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Authors
Rabab Said Ibrahim email orcid 1; Magda M.F. Ismailorcid 2; Taghreed Zakaria Shawer3; Yossry Ahmed Ammar4
1Pharmaceutical Medicinal Chemistry department, Faculty of Pharmacy (Girls), Al-Azhar university
2professor, Department of Pharmaceutical Medicinal Chemistry and Drug Design, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, Egypt
3Pharmaceutical medicinal chemistry and drug design department. Faculty of pharmacy (girls), Al Azhar University, Cairo, Egypt.
4Department of Chemistry, Faculty of Science 11754 Al-Azhar University, Cairo, Egypt.
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.
Keywords
Quinoxaline; MTT; Docking; Anticancer; ADME
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