Copper-Catalyzed Asymmetric Hydroboration Reaction of Novel Methylene Isoindolinone Compounds through Microwave Irradiation and Their Antileishmanial and Antitoxoplasma Activities

Hamida Jellali; Nasser Amri; Yousef E Mukhrish; Ibrahim S Al Nasr; Waleed S Koko; Tariq A Khan; Eric Deniau; Mathieu Sauthier; Houcine Ghalla; Naceur Hamdi

doi:10.1021/acsomega.3c02362

Copper-Catalyzed Asymmetric Hydroboration Reaction of Novel Methylene Isoindolinone Compounds through Microwave Irradiation and Their Antileishmanial and Antitoxoplasma Activities

ACS Omega. 2023 Jun 9;8(25):23067-23077. doi: 10.1021/acsomega.3c02362. eCollection 2023 Jun 27.

Authors

Hamida Jellali¹, Nasser Amri², Yousef E Mukhrish², Ibrahim S Al Nasr^{3

4}, Waleed S Koko⁴, Tariq A Khan⁵, Eric Deniau⁶, Mathieu Sauthier⁶, Houcine Ghalla⁷, Naceur Hamdi⁸

Affiliations

¹ Research Laboratory of Environmental Sciences and Technologies (LR16ES09), Higher Institute of Environmental Sciences and Technology, University of Carthage, Hammam-Lif, Tunis 2078, Tunisia.
² Department of Chemistry, Faculty of Science, Jazan University, Jazan 45142, Saudi Arabia.
³ Department of Biology, College of Science and Arts, Qassim University, Unaizah 51911, Saudi Arabia.
⁴ Department of Science Laboratories, College of Science and Arts, Qassim University, Ar Rass 51921, Saudi Arabia.
⁵ Department of Clinical Nutrition, College of Applied Health Sciences, Qassim University, Ar Rass 51921, Saudi Arabia.
⁶ University of Lille, CNRS, Centrale Lille, Université Artois, UMR 8181-UCCS-Unité de Catalyze et Chimie du Solide, Lille 59000, France.
⁷ Quantum and Statistical Physics Laboratory, Faculty of Sciences, University of Monastir, Monastir 5000, Tunisia.
⁸ Department of Chemistry, College of Science and Arts, Qassim University, Ar Rass 51921 Saudi Arabia.

Abstract

The aim of this study was devoted into molecular docking calculations to discover the potential antileishmania and antitoxoplasma activities of newly synthesized compounds obtained by applying a practical and simple method under microwave irradiation. All these compounds were tested in vitro for their biological activity against Leishmania major promastigotes, amastigotes, and Toxoplasma gondii tachyzoites. Compounds 2a, 5a, and 5e were the most active against both L. major promastigotes and amastigotes, with IC₅₀ values of less than 0.4 μM mL^-1. Compounds 2c, 2e, 2h, and 5d had a strong antitoxoplasma activity of less than 2.1 μM mL^-1 against T. gondii. We can conclude that aromatic methyleneisoindolinones are potently active against both L. major and T. gondii. Further studies for mode of action evaluation are recommended. Compounds 5c and 5b are the best drug candidates for antileishmania and antitoxoplasma due to their SI values being over 13. The docking studies of compounds 2a-h and 5a-e against pteridine reductase 1 and T. gondii enoyl acyl carrier protein reductase reveal that compound 5e may be an effective antileishmanial and antitoxoplasma drug discovery initiative.