Design, synthesis, in vitro, and in silico study of benzothiazole-based compounds as a potent anti-Alzheimer agent.

Autor: Jalil S; Centre for Advanced Drug Research, Department of Pharmacy, COMSATS University Islamabad, Abbottabad Campus, Abbottabad, 22060, Pakistan.; Department of Pharmacy, COMSATS University Islamabad, Abbottabad Campus, Abbottabad, 22060, Pakistan., Shabir G; Department of Chemistry, Quaid-I-Azam University, Islamabad, 45320, Pakistan. shabirg@yahoo.com., Saeed A; Department of Chemistry, Quaid-I-Azam University, Islamabad, 45320, Pakistan. shabirg@yahoo.com., Iqbal J; Centre for Advanced Drug Research, Department of Pharmacy, COMSATS University Islamabad, Abbottabad Campus, Abbottabad, 22060, Pakistan.; Department of Pharmacy, COMSATS University Islamabad, Abbottabad Campus, Abbottabad, 22060, Pakistan.; Department of Chemistry, COMSATS University Islamabad, Abbottabad Campus, Abbottabad, 22060, Pakistan.
Jazyk: angličtina
Zdroj: Molecular diversity [Mol Divers] 2024 Oct 07. Date of Electronic Publication: 2024 Oct 07.
DOI: 10.1007/s11030-024-10909-6
Abstrakt: Alzheimer's disease (AD) is a multifactorial neurological disorder that involves multiple enzymes in the process of developing. Conventional monotherapies provide relief, necessitating alternative multi-targeting approaches to address AD complexity. Therefore, we synthesize N-(benzo[d]thiazol-2-yl) benzamide-based compounds and tested against monoamine oxidases (MAO-A and MAO-B). In the in vitro experimental evaluation of MAO, all the compounds displayed remarkable potency, having IC 50 values in the lower micromolar range. The most potent MAO-A inhibitor was (3e) with an IC 50 value of 0.92 ± 0.09 μM, whereas, (3d) was the most potent inhibitor of MAO-B with an IC 50 value of 0.48 ± 0.04 μM. Moreover, Enzyme kinetics studies revealed that the potent inhibitors of MAO-A and MAO-B showed competitive mode of inhibition. Furthermore, molecular docking studies were also performed to confirm the mode of inhibition and obtain an intuitive picture of potent inhibitors. It also revealed several important interactions, particularly hydrogen bonding interaction. All the newly synthesized compounds showed good ADME pharmacokinetic profile and followed Lipinski rule; these compounds represent promising hits for the development of promising lead compounds for AD treatment.
(© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)
Databáze: MEDLINE
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