Curcumin-based Antioxidant and Glycohydrolase Inhibitor Compounds: Synthesis and In Vitro Appraisal of the Dual Activity Against Diabetes.


Journal

Medicinal chemistry (Shariqah (United Arab Emirates))
ISSN: 1875-6638
Titre abrégé: Med Chem
Pays: Netherlands
ID NLM: 101240303

Informations de publication

Date de publication:
2021
Historique:
received: 27 09 2019
revised: 07 03 2020
accepted: 25 03 2020
pubmed: 7 5 2020
medline: 4 9 2021
entrez: 7 5 2020
Statut: ppublish

Résumé

Curcumin, as the substantial constituent of the turmeric plant (Curcuma longa), plays a significant role in the prevention of various diseases, including diabetes. It possesses ideal structure features as an enzyme inhibitor, including a flexible backbone, hydrophobic nature, and several available hydrogen bond (H-bond) donors and acceptors. The present study aimed at synthesizing several novel curcumin derivatives and further evaluation of these compounds for possible antioxidant and anti-diabetic properties along with inhibitory effect against two carbohydrate-hydrolyzing enzymes, α-amylase and α-glucosidase, as these enzymes are therapeutic targets for attenuation of postprandial hyperglycemia. Therefore, curcumin-based pyrido[2,3-d]pyrimidine derivatives were synthesized and identified using an instrumental technique like NMR spectroscopy and then screened for antioxidant and enzyme inhibitory potential. Total antioxidant activity, reducing power assay and 1,1-diphenyl-2- picrylhydrazyl (DPPH•) radical scavenging activity were done to appraise the antioxidant potential of these compounds in vitro. Compounds L6-L9 showed higher antioxidant activity while L4, L9, L12 and especially L8 exhibited the best selectivity index (lowest α-amylase/α-glucosidase inhibition ratio). These antioxidant inhibitors may be potential anti-diabetic drugs, not only to reduce glycemic index but also to limit the activity of the major reactive oxygen species (ROS) producing pathways.

Sections du résumé

BACKGROUND BACKGROUND
Curcumin, as the substantial constituent of the turmeric plant (Curcuma longa), plays a significant role in the prevention of various diseases, including diabetes. It possesses ideal structure features as an enzyme inhibitor, including a flexible backbone, hydrophobic nature, and several available hydrogen bond (H-bond) donors and acceptors.
OBJECTIVE OBJECTIVE
The present study aimed at synthesizing several novel curcumin derivatives and further evaluation of these compounds for possible antioxidant and anti-diabetic properties along with inhibitory effect against two carbohydrate-hydrolyzing enzymes, α-amylase and α-glucosidase, as these enzymes are therapeutic targets for attenuation of postprandial hyperglycemia.
METHODS METHODS
Therefore, curcumin-based pyrido[2,3-d]pyrimidine derivatives were synthesized and identified using an instrumental technique like NMR spectroscopy and then screened for antioxidant and enzyme inhibitory potential. Total antioxidant activity, reducing power assay and 1,1-diphenyl-2- picrylhydrazyl (DPPH•) radical scavenging activity were done to appraise the antioxidant potential of these compounds in vitro.
RESULTS RESULTS
Compounds L6-L9 showed higher antioxidant activity while L4, L9, L12 and especially L8 exhibited the best selectivity index (lowest α-amylase/α-glucosidase inhibition ratio).
CONCLUSION CONCLUSIONS
These antioxidant inhibitors may be potential anti-diabetic drugs, not only to reduce glycemic index but also to limit the activity of the major reactive oxygen species (ROS) producing pathways.

Identifiants

pubmed: 32370719
pii: MC-EPUB-106397
doi: 10.2174/1573406416666200506083718
doi:

Substances chimiques

Antioxidants 0
Glycoside Hydrolase Inhibitors 0
Hypoglycemic Agents 0
Glycoside Hydrolases EC 3.2.1.-
Curcumin IT942ZTH98

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

677-698

Subventions

Organisme : Research Council of Kermanshah University of Medical Sciences (KUMS)
ID : 95423

Informations de copyright

Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.

Auteurs

Sajjad Esmaeili (S)

Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Nazanin Ghobadi (N)

Department of Chemistry, School of Science, Alzahra University, Vanak, Tehran, Iran.

Donya Nazari (D)

Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Alireza Pourhossein (A)

Nano Drug Delivery Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Hassan Rasouli (H)

Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Hadi Adibi (H)

Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Reza Khodarahmi (R)

Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.

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Classifications MeSH