Design, synthesis and bioevaluation of new vanillin hybrid as multitarget inhibitor of α-glucosidase, α-amylase, PTP-1B and DPP4 for the treatment of type-II diabetes.

Autor: Huneif MA; Pediatric Department, Medical College, Najran University, Najran, Saudi Arabia. Electronic address: huneif@hotmail.com., Alshehri DB; Pediatric Department, Medical College, Najran University, Najran, Saudi Arabia. Electronic address: dr.zhafer@hotmail.com., Alshaibari KS; Pediatric Department, Medical College, Najran University, Najran, Saudi Arabia. Electronic address: Khalid22ye@gmail.com., Dammaj MZ; Pediatric Department, Medical College, Najran University, Najran, Saudi Arabia. Electronic address: mayasadammaj@gmail.com., Mahnashi MH; Department of Pharmaceutical Chemistry, College of Pharmacy, Najran University, Najran, Saudi Arabia. Electronic address: matermaha@gmail.com., Majid SU; Department of Chemistry, COMSATS University Islamabad, Abbottabad Campus, 22060 Abbottabad, Pakistan. Electronic address: safeullahmajid@gmail.com., Javed MA; Department of Chemistry, COMSATS University Islamabad, Abbottabad Campus, 22060 Abbottabad, Pakistan. Electronic address: amirjaved55@gmail.com., Ahmad S; Department of Pharmacy, Faculty of Biological Sciences, University of Malakand, Dir (L), Chakdara 18000, KP, Pakistan. Electronic address: drsajjaduom@gmail.com., Rashid U; Department of Chemistry, COMSATS University Islamabad, Abbottabad Campus, 22060 Abbottabad, Pakistan. Electronic address: umerrashid@cuiatd.edu.pk., Sadiq A; Department of Pharmacy, Faculty of Biological Sciences, University of Malakand, Dir (L), Chakdara 18000, KP, Pakistan. Electronic address: sadiquom@yahoo.com.
Jazyk: angličtina
Zdroj: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2022 Jun; Vol. 150, pp. 113038. Date of Electronic Publication: 2022 Apr 28.
DOI: 10.1016/j.biopha.2022.113038
Abstrakt: Diabetes mellitus (DM) is a real challenge to the recent era and is one of the major diseases for initiating life-threatening disorders. In current research, a compound was designed by combining vanillin, thiazolidinedione and morpholine. The goal of our designed work is to demonstrate the ability of our design compound (9) to modulate more than one target responsible for hyperglycemia at the same time. The synthesized compound was able to show good to moderate inhibition potential against α-glucosidase, α-amylase and protein tyrosine phosphatase 1B. However, it exhibited excellent in-vitro inhibition of Dipeptidyl peptidase-4 (DPP-4) with IC 50 value of 0.09 µM. Antioxidant activity by using DPPH assay also showed its good antioxidant potential. In in-vivo experiments, the compound 9 was proved to be safe in experimental mice. The activity profile of the compound was observed for 21 days which showed that the compound was also effective in experimental mice. Binding orientations and Interactions with key amino acid residues of the selected targets were also studied by using docking studies. Overall, we were successful in synthesizing multitarget preclinical therapeutic by combining three pharmacophoric moieties into a single chemical entity that can modulate more than one target at the same time.
(Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
Databáze: MEDLINE
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