Synthesis, in vitro, and in silico studies of new derivatives of diphenylpiperazine scaffold: A key substructure for MAO inhibition.

Autor: El-Halaby LO; Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura University, P.O. Box 35516, Mansoura, Egypt., El-Husseiny WM; Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura University, P.O. Box 35516, Mansoura, Egypt., El-Messery SM; Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura University, P.O. Box 35516, Mansoura, Egypt. Electronic address: habib2001@mans.edu.eg., Goda FE; Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura University, P.O. Box 35516, Mansoura, Egypt.
Jazyk: angličtina
Zdroj: Bioorganic chemistry [Bioorg Chem] 2024 Feb; Vol. 143, pp. 107011. Date of Electronic Publication: 2023 Dec 03.
DOI: 10.1016/j.bioorg.2023.107011
Abstrakt: Fifteen new diphenylpiperazine hybrids were designed, synthesized and in vitro biologically evaluated against hMAOs enzymes via fluorometric method. All of our new compounds displayed strong inhibitory activities against both two isoforms of hMAOs with IC 50 range of 0.091-16.32 µM. According to selectivity index values, all hybrids showed higher selectivity against hMAO-A over hMAO-B. Compound 8 exhibited the best hMAO-A inhibition activity (IC 50 value = 91 nM, SI = 19.55). With a selectivity index of 31.02 folds over MAO-B, compound 7 was revealed to be the most effective hMAO-A inhibitor. In silico prediction of physicochemical parameters and BBB permeability proved that all of the newly synthesized compounds have favorable pharmacokinetic profiles and acceptable ADME properties and can pass BBB. For clarification and explanation of the biological activity of compounds 7 and 8, molecular docking simulations were carried out. In light of this, 1,4-diphenylpiperazine analogues can be seen as an encouraging lead to develop safe and effective new drugs for treatment of many disorders such as anxiety and depression by inhibition of hMAO-A enzyme.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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