Synthesis, in Vitro, and in Silico Studies of Newly Functionalized Quinazolinone Analogs for the Identification of Potent Α-Glucosidase Inhibitors

Synthesis, in Vitro, and in Silico Studies of Newly Functionalized Quinazolinone Analogs for the Identification of Potent Α-Glucosidase Inhibitors Publisher

Wali H¹ ; Anwar A² ; Shamim S¹ ; Khan KM^{1, 3} ; Mahdavi M⁴ ; Salar U⁵ ; Larijani B⁴ ; Perveen S⁶ ; Taha M³ ; Faramarzi MA⁷

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1. H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan
2. Department of Biological Sciences, School of Science and Technology, Sunway University, Subang Jaya, Selangor, 47500, Malaysia
3. Department of Clinical Pharmacy, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam, 31441, Saudi Arabia
4. Endocrinology and Metabolism Research Institute, Tehran University of Medical Sciences, Tehran, Iran
5. Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan
6. PCSIR Laboratories Complex, Karachi, Shahrah-e-Dr. Salimuzzaman Siddiqui, Karachi, 75280, Pakistan
7. Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

Source: Journal of the Iranian Chemical Society Published:2021

Abstract

Functionalized quinazolinone derivatives 1–30 were synthesized by two-step reaction. First, anthranilic acid was treated with substituted phenyl isothiocyanate to synthesize 3-aryl-2-thioxo-2,3-dihydroquinazolinone derivatives 1–8 which in turn reacted with different bromoacetophenone derivatives to obtain fully functionalized quinazolinone derivatives 9–30. Both reactions were catalyzed by triethylamine. All the products were characterized by EI-, HREI-MS, 1H-, and 13CNMR spectroscopic techniques. All compounds were subjected to their in vitro α-glucosidase inhibitory activity. Results showed that except compound 1–3, 5, 7, and 22, all compounds were found potent and showed many folds increased α-glucosidase enzyme inhibition as compared to standard acarbose (IC50 = 750.0 ± 10.0 µM). Compound 13 (IC50 = 85.0 ± 0.5 µM) was recognized as the most potent analog of the whole series, with ninefold enhanced inhibitory potential than the standard acarbose. Compounds 1–9, 11, 12, 22, and 26 were structurally known compounds, while remaining all are new. Kinetic study on compound 13 showed that the compound is following a competitive-type inhibition mechanism. Furthermore, in silico studies have also been performed to better rationalize the interactions between synthetic compound and active site of the enzyme. Graphic abstract: [Figure not available: see fulltext.] © 2021, Iranian Chemical Society.

Style	Citing Format
MLA	Wali H, et al.. "Synthesis, in Vitro, and in Silico Studies of Newly Functionalized Quinazolinone Analogs for the Identification of Potent Α-Glucosidase Inhibitors." Journal of the Iranian Chemical Society, vol. 18, no. 8, 2021, pp. 2017-2034.
APA	Wali H, Anwar A, Shamim S, Khan KM, Mahdavi M, Salar U, Larijani B, Perveen S, Taha M, Faramarzi MA (2021). Synthesis, in Vitro, and in Silico Studies of Newly Functionalized Quinazolinone Analogs for the Identification of Potent Α-Glucosidase Inhibitors. Journal of the Iranian Chemical Society, 18(8), 2017-2034.
Chicago	Wali H, Anwar A, Shamim S, Khan KM, Mahdavi M, Salar U, Larijani B, Perveen S, Taha M, Faramarzi MA. "Synthesis, in Vitro, and in Silico Studies of Newly Functionalized Quinazolinone Analogs for the Identification of Potent Α-Glucosidase Inhibitors." Journal of the Iranian Chemical Society 18, no. 8 (2021): 2017-2034.
Harvard	Wali H et al. (2021) 'Synthesis, in Vitro, and in Silico Studies of Newly Functionalized Quinazolinone Analogs for the Identification of Potent Α-Glucosidase Inhibitors', Journal of the Iranian Chemical Society, 18(8), pp. 2017-2034.
Vancouver	Wali H, Anwar A, Shamim S, Khan KM, Mahdavi M, Salar U, et al.. Synthesis, in Vitro, and in Silico Studies of Newly Functionalized Quinazolinone Analogs for the Identification of Potent Α-Glucosidase Inhibitors. Journal of the Iranian Chemical Society. 2021;18(8):2017-2034.
BibTex	@article{ author = {Wali H and Anwar A and Shamim S and Khan KM and Mahdavi M and Salar U and Larijani B and Perveen S and Taha M and Faramarzi MA}, title = {Synthesis, in Vitro, and in Silico Studies of Newly Functionalized Quinazolinone Analogs for the Identification of Potent Α-Glucosidase Inhibitors}, journal = {Journal of the Iranian Chemical Society}, volume = {18}, number = {8}, pages = {2017-2034}, year = {2021} }
RIS	TY - JOUR AU - Wali H AU - Anwar A AU - Shamim S AU - Khan KM AU - Mahdavi M AU - Salar U AU - Larijani B AU - Perveen S AU - Taha M AU - Faramarzi MA TI - Synthesis, in Vitro, and in Silico Studies of Newly Functionalized Quinazolinone Analogs for the Identification of Potent Α-Glucosidase Inhibitors JO - Journal of the Iranian Chemical Society VL - 18 IS - 8 SP - 2017 EP - 2034 PY - 2021 ER -

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