Discovery of imidazopyridine derived oxadiazole-based thiourea derivatives as potential anti-diabetic agents: Synthesis, in vitro antioxidant screening and in silico molecular modeling approaches

A series of new imidazopyridine based oxadiazole derivatives (5a-l) were designed and synthesized. Their structures were confirmed by spectral data and then subjected to in vitro assessment including α-glucosidase, α-amylase inhibitory, and 2- diphenyl-1-picrylhydrazyl (DDPH) and 2,2′-azinobis(3-eth...

Full description

Bibliographic Details
Published in:Journal of Molecular Structure
Main Author: Hussain R.; Rehman W.; Rahim F.; Khan S.; Taha M.; Khan Y.; Sardar A.; Khan I.; Shah S.A.A.
Format: Article
Language:English
Published: Elsevier B.V. 2023
Online Access:https://www.scopus.com/inward/record.uri?eid=2-s2.0-85167451003&doi=10.1016%2fj.molstruc.2023.136185&partnerID=40&md5=0451bef5822edc3be370c2ee7e0f0f9c
id 2-s2.0-85167451003
spelling 2-s2.0-85167451003
Hussain R.; Rehman W.; Rahim F.; Khan S.; Taha M.; Khan Y.; Sardar A.; Khan I.; Shah S.A.A.
Discovery of imidazopyridine derived oxadiazole-based thiourea derivatives as potential anti-diabetic agents: Synthesis, in vitro antioxidant screening and in silico molecular modeling approaches
2023
Journal of Molecular Structure
1293

10.1016/j.molstruc.2023.136185
https://www.scopus.com/inward/record.uri?eid=2-s2.0-85167451003&doi=10.1016%2fj.molstruc.2023.136185&partnerID=40&md5=0451bef5822edc3be370c2ee7e0f0f9c
A series of new imidazopyridine based oxadiazole derivatives (5a-l) were designed and synthesized. Their structures were confirmed by spectral data and then subjected to in vitro assessment including α-glucosidase, α-amylase inhibitory, and 2- diphenyl-1-picrylhydrazyl (DDPH) and 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging activities. The inhibitory activity results revealed that all the synthesized analogs displayed significant α-glucosidase and α-amylase inhibition with IC50 values of 0.90 ± 0.10 to 18.10 ± 0.20 µM (for α-glucosidase) and 1.10 ± 0.10 to 19.70 ± 0.20 µM (for α-amylase) respectively as compared to standard acarbose with IC50 values of 11.50 ± 0.30 µM (α-glucosidase) and 12.20 ± 0.30 µM (for α-amylase).The synthesized analogs also showed significant DPPH and ABTS radical scavenging activities with IC50 values in the range of 1.05 ± 0.05 to 4.56 ± 3.12 µM (for DDPH) and 1.15 ± 0.05 to 4.89 ± 2.89 µM (for ABTS) respectively, incomparison to standard ascorbic acid with IC50 = 1.83 ± 1.32 µM (for DDPH) and 1.84 ± 1.16 µM (for ABTS) respectively. After crucial analysis of varying substitution effects on inhibitory (α-glucosidase &α-amylase) and radical scavenging (DPPH & ABTS) potentials respectively, the structure-activity relationship (SAR) was established. Through the in silico molecular docking analysis, the ability of the synthesized analogs to inhibit α-glucosidase and α -amylase was also examined.There was a good correlation between in vitro and in silico studies for synthesized analogs 5i and 5d Further studies are required to determine whether these potent analogs could be a potential treatment for diabetes disease. © 2023 Elsevier B.V.
Elsevier B.V.
222860
English
Article

author Hussain R.; Rehman W.; Rahim F.; Khan S.; Taha M.; Khan Y.; Sardar A.; Khan I.; Shah S.A.A.
spellingShingle Hussain R.; Rehman W.; Rahim F.; Khan S.; Taha M.; Khan Y.; Sardar A.; Khan I.; Shah S.A.A.
Discovery of imidazopyridine derived oxadiazole-based thiourea derivatives as potential anti-diabetic agents: Synthesis, in vitro antioxidant screening and in silico molecular modeling approaches
author_facet Hussain R.; Rehman W.; Rahim F.; Khan S.; Taha M.; Khan Y.; Sardar A.; Khan I.; Shah S.A.A.
author_sort Hussain R.; Rehman W.; Rahim F.; Khan S.; Taha M.; Khan Y.; Sardar A.; Khan I.; Shah S.A.A.
title Discovery of imidazopyridine derived oxadiazole-based thiourea derivatives as potential anti-diabetic agents: Synthesis, in vitro antioxidant screening and in silico molecular modeling approaches
title_short Discovery of imidazopyridine derived oxadiazole-based thiourea derivatives as potential anti-diabetic agents: Synthesis, in vitro antioxidant screening and in silico molecular modeling approaches
title_full Discovery of imidazopyridine derived oxadiazole-based thiourea derivatives as potential anti-diabetic agents: Synthesis, in vitro antioxidant screening and in silico molecular modeling approaches
title_fullStr Discovery of imidazopyridine derived oxadiazole-based thiourea derivatives as potential anti-diabetic agents: Synthesis, in vitro antioxidant screening and in silico molecular modeling approaches
title_full_unstemmed Discovery of imidazopyridine derived oxadiazole-based thiourea derivatives as potential anti-diabetic agents: Synthesis, in vitro antioxidant screening and in silico molecular modeling approaches
title_sort Discovery of imidazopyridine derived oxadiazole-based thiourea derivatives as potential anti-diabetic agents: Synthesis, in vitro antioxidant screening and in silico molecular modeling approaches
publishDate 2023
container_title Journal of Molecular Structure
container_volume 1293
container_issue
doi_str_mv 10.1016/j.molstruc.2023.136185
url https://www.scopus.com/inward/record.uri?eid=2-s2.0-85167451003&doi=10.1016%2fj.molstruc.2023.136185&partnerID=40&md5=0451bef5822edc3be370c2ee7e0f0f9c
description A series of new imidazopyridine based oxadiazole derivatives (5a-l) were designed and synthesized. Their structures were confirmed by spectral data and then subjected to in vitro assessment including α-glucosidase, α-amylase inhibitory, and 2- diphenyl-1-picrylhydrazyl (DDPH) and 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging activities. The inhibitory activity results revealed that all the synthesized analogs displayed significant α-glucosidase and α-amylase inhibition with IC50 values of 0.90 ± 0.10 to 18.10 ± 0.20 µM (for α-glucosidase) and 1.10 ± 0.10 to 19.70 ± 0.20 µM (for α-amylase) respectively as compared to standard acarbose with IC50 values of 11.50 ± 0.30 µM (α-glucosidase) and 12.20 ± 0.30 µM (for α-amylase).The synthesized analogs also showed significant DPPH and ABTS radical scavenging activities with IC50 values in the range of 1.05 ± 0.05 to 4.56 ± 3.12 µM (for DDPH) and 1.15 ± 0.05 to 4.89 ± 2.89 µM (for ABTS) respectively, incomparison to standard ascorbic acid with IC50 = 1.83 ± 1.32 µM (for DDPH) and 1.84 ± 1.16 µM (for ABTS) respectively. After crucial analysis of varying substitution effects on inhibitory (α-glucosidase &α-amylase) and radical scavenging (DPPH & ABTS) potentials respectively, the structure-activity relationship (SAR) was established. Through the in silico molecular docking analysis, the ability of the synthesized analogs to inhibit α-glucosidase and α -amylase was also examined.There was a good correlation between in vitro and in silico studies for synthesized analogs 5i and 5d Further studies are required to determine whether these potent analogs could be a potential treatment for diabetes disease. © 2023 Elsevier B.V.
publisher Elsevier B.V.
issn 222860
language English
format Article
accesstype
record_format scopus
collection Scopus
_version_ 1809678476395937792