Unveiling potent Schiff base derivatives with selective xanthine oxidase inhibition: In silico and in vitro approach

Fatna Bellahcene; Khedidja Benarous; Arif Mermer; Houssem Boulebd; Talia Serseg; Abderahmane Linani; Alaeddine Kaouka; Mohamed Yousfi; Asad Syed; Abdallah M Elgorban; Yasuhiro Ozeki; Sarkar M A Kawsar

doi:10.1016/j.jsps.2024.102062

Unveiling potent Schiff base derivatives with selective xanthine oxidase inhibition: In silico and in vitro approach

Saudi Pharm J. 2024 May;32(5):102062. doi: 10.1016/j.jsps.2024.102062. Epub 2024 Apr 4.

Authors

Fatna Bellahcene¹, Khedidja Benarous¹, Arif Mermer^{2

3

4}, Houssem Boulebd⁵, Talia Serseg^{1

6}, Abderahmane Linani¹, Alaeddine Kaouka⁶, Mohamed Yousfi¹, Asad Syed⁷, Abdallah M Elgorban⁷, Yasuhiro Ozeki⁸, Sarkar M A Kawsar⁹

Affiliations

¹ Laboratory of Fundamental Sciences, Faculty of Sciences, University of Amar Telidji, Laghouat, Algeria.
² Department of Biotechnology, University of Health Sciences, İstanbul, Turkey.
³ Experimental Medicine Application and Research Center, Validebag Research Park, University of Health Sciences, İstanbul, Turkey.
⁴ Department of Pharmacy, University of Health Sciences, İstanbul, Turkey.
⁵ Department of Chemistry, Faculty of Exact Sciences, University of Constantine 1, Constantine, Algeria.
⁶ Laboratoire des Sciences Appliquées et Didactiques, Ecole Normale Supérieure de Laghouat, Algeria.
⁷ Department of Botany and Microbiology, College of Science, King Saud University, P.O. 2455, Riyadh 11451, Saudi Arabia.
⁸ Graduate School of NanoBio Sciences, Yokohama City University, 22-2 Seto, Kanazawa-ku, Yokohama 236-0027, Japan.
⁹ Laboratory of Carbohydrate and Nucleoside Chemistry, Department of Chemistry, Faculty of Science, University of Chittagong, Chittagong 4331, Bangladesh.

Abstract

This research describes the synthesis by an environmentally-friendly method, microwave irradiation, development and analysis of three novel and one previously identified Schiff base derivative as a potential inhibitor of bovine xanthine oxidase (BXO), a key enzyme implicated in the progression of gout. Meticulous experimentation revealed that these compounds (10, 9, 4, and 7) have noteworthy inhibitory effects on BXO, with IC50 values ranging from 149.56 µM to 263.60 µM, indicating their good efficacy compared to that of the standard control. The validation of these results was further enhanced through comprehensive in silico studies, which revealed the pivotal interactions between the inhibitors and the catalytic sites of BXO, with a particular emphasis on the imine group (-C = N-) functionalities. Intriguingly, the compounds exhibiting the highest inhibition rates also showcase advantageous ADMET profiles, alongside encouraging initial assessments via PASS, hinting at their broad-spectrum potential. The implications of these findings are profound, suggesting that these Schiff base derivatives not only offer a new vantage point for the inhibition of BXO but also hold considerable promise as innovative therapeutic agents in the management and treatment of gout, marking a significant leap forward in the quest for more effective gout interventions.

Keywords: Gout; In silico approach; Schiff base; Triazole; Xanthine oxidase inhibition.