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Structure Based Design of Some Novel 3-Methylquinoxaline Derivatives Through Molecular Docking and Pharmacokinetics Studies as Novel VEGFR-2 Inhibitors

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Abstract

Cancer is alleged to be the second major mortality inflicting malady according to the world health organization (WHO) reports. Even though there are high advances in the diagnosis and remedy of this ailment, the patient’s survival ratio remains unsatisfactory as a result of the prevalent antagonistic effects of anticancer drugs. Hence, the discovery of new, effective, selective, and much less toxic anticancer agents is still mandatory. In this study we report the design of new 3-methylquinoxaline derivatives for the inhibition of VEGFR-2 receptors through molecular docking and structural modification of the template compound. The results of docking study performed between forty one series of 3-methylquinoxaline derivatives and the active site of the VEGFR-2 target receptor (pdb id = 2OH4) illustrates that five compounds (5, 27, 33, 37 and 40) showed higher MolDock and Rerank scores than Sorafenib (control drug), as such they were tagged as the potential hit compounds. Compound 5 having the highest docking scores (MolDock score = -156.063, Rerank score = -133.13) with good pharmacokinetic profile, and drug-likeness properties was utilized as a template for the design of eight new novel 3-methyl quinoxaline derivatives. All the designed compounds were found to have better docking scores ranging from − 156.966 to -167.961 Moldock scores and − 133.485 to -137.852 Rerank scores compared to the template compound (Moldock score = -156.063, Rerank score = -133.13) and Sorafenib (Moldock score = -146.535, Rerank score = -102.625). The designed compounds do not violate the acceptable criteria set by Lipinski, hence, they are easily transported, absorbed and diffused in to the human system. Additionally, they have low predicted synthetic accessibility values ranging from 3.29 to 3.85 indicating that they are easily synthesized in the laboratory and high bioavailability scores of 0.55 which revealed that they are orally bioavailable. Hence, the designed 3-methylquinoxaline derivatives can serve as better VEGFR-2 inhibitors.

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Authors and Affiliations

  1. Department of Chemistry, Faculty of Physical Sciences, Ahmadu Bello University, P.M.B.1045, Zaria, Kaduna State, Nigeria

    Sagiru Hamza Abdullahi, Adamu Uzairu, Gideon Adamu Shallangwa, Sani Uba & Abdullahi Bello Umar

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  1. Sagiru Hamza Abdullahi
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  2. Adamu Uzairu
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  3. Gideon Adamu Shallangwa
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Abdullahi, S.H., Uzairu, A., Shallangwa, G.A. et al. Structure Based Design of Some Novel 3-Methylquinoxaline Derivatives Through Molecular Docking and Pharmacokinetics Studies as Novel VEGFR-2 Inhibitors. Chemistry Africa 5, 1967–1978 (2022). https://doi.org/10.1007/s42250-022-00485-3

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