New N-Alkylated Heterocyclic Compounds as Prospective NDM1 Inhibitors: Investigation of In Vitro and In Silico Properties

Yassine Kaddouri; Btissam Bouchal; Farid Abrigach; Mohamed El Kodadi; Mohammed Bellaoui; Ahmed Elkamhawy; Rachid Touzani; Magda H Abdellattif

doi:10.3390/ph15070803

New N-Alkylated Heterocyclic Compounds as Prospective NDM1 Inhibitors: Investigation of In Vitro and In Silico Properties

Pharmaceuticals (Basel). 2022 Jun 28;15(7):803. doi: 10.3390/ph15070803.

Authors

Yassine Kaddouri¹, Btissam Bouchal², Farid Abrigach³, Mohamed El Kodadi^{3

4}, Mohammed Bellaoui², Ahmed Elkamhawy^{5

6}, Rachid Touzani³, Magda H Abdellattif⁷

Affiliations

¹ Laboratory of Inorganic Chemistry, Department of Chemistry, University of Helsinki, P.O. Box 55, FI-00014 Helsinki, Finland.
² Genetics Unit, Medical Sciences Research Laboratory, Faculty of Medicine and Pharmacy of Oujda, University Mohammed Premier, Oujda 11022, Morocco.
³ Laboratory of Applied Chemistry & Environment (LCAE), Faculty of Sciences, University Mohammed Premier, Oujda 11022, Morocco.
⁴ CRMEF Oriental, Center régional des Métiers de l'Education et de Formation, Oujda 11022, Morocco.
⁵ BK21 FOUR Team and Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University-Seoul, Goyang 10326, Korea.
⁶ Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
⁷ Chemistry Department, Sciences College, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.

Abstract

A new family of pyrazole-based compounds (1-15) was synthesized and characterized using different physicochemical analyses, such as FTIR, UV-Visible, ¹H, ¹³C NMR, and ESI/LC-MS. The compounds were evaluated for their in vitro antifungal and antibacterial activities against several fungal and bacterial strains. The results indicate that some compounds showed excellent antibacterial activity against E. coli, S. aureus, C. freundii, and L. monocytogenes strains. In contrast, none of the compounds had antifungal activity. Molecular electrostatic potential (MEP) map analyses and inductive and mesomeric effect studies were performed to study the relationship between the chemical structure of our compounds and the biological activity. In addition, molecular docking and virtual screening studies were carried out to rationalize the antibacterial findings to characterize the modes of binding of the most active compounds to the active pockets of NDM1 proteins.

Keywords: ADME-Tox; antibacterial; antifungal; molecular docking; pyrazole; synthesis.

Grants and funding

TURSP2020/91/Taif University