6533b852fe1ef96bd12aaed3
RESEARCH PRODUCT
Synthesis of Rosmarinic Acid Amides as Antioxidative and Hypoglycemic Agents
Antonio RescifinaSergio RosselliGiuseppe FlorestaCorrado TringaliVera MuccilliNunzio CardulloGiorgia CatinellaMaurizio Brunosubject
3003DrugAntioxidantDPPHProton Magnetic Resonance Spectroscopymedia_common.quotation_subjectmedicine.medical_treatmentPharmaceutical ScienceOxidative phosphorylationPharmacologyDepsides01 natural sciencesAntioxidantsAnalytical Chemistrychemistry.chemical_compoundDrug DiscoverymedicineHypoglycemic AgentsSettore BIO/15 - Biologia FarmaceuticaCarbon-13 Magnetic Resonance SpectroscopyIC50media_commonAcarbosePharmacology010405 organic chemistrydiabetes mellituDrug Discovery3003 Pharmaceutical ScienceRosmarinic acidOrganic ChemistrySettore CHIM/06 - Chimica OrganicaComplementary and Alternative Medicine2708 DermatologyAmidesamide0104 chemical sciences010404 medicinal & biomolecular chemistryRosmarinic acidComplementary and alternative medicinechemistryCinnamatesPolyphenolAnalytical Chemistry; Molecular Medicine; Pharmacology; 3003; Drug Discovery3003 Pharmaceutical Science; Complementary and Alternative Medicine2708 Dermatology; Organic ChemistryMolecular Medicineα-glucosidasemedicine.drugdescription
Type 2 diabetes mellitus (T2DM) is an important metabolic disorder for which there is an urgent need for new antidiabetic drugs. α-Glucosidase inhibition is an established protocol for T2DM therapy. Because hyperglycemia causes oxidative tissue damage, the development of agents with both α-glucosidase inhibition and antioxidant activity from natural or natural-derived polyphenols such derivatives of rosmarinic acid (RA) represents an attractive therapeutic option. We report a study on amides 1-10 derived from RA and their evaluation for yeast α-glucosidase inhibition and antioxidant activity (DPPH and ORAC tests). All amides showed higher inhibitory activity than that of RA, were by far more potent than the antidiabetic drug acarbose, and proved to be effective antioxidants. A molecular docking study displayed significant binding interactions of RA amides with the active site of α-glucosidase. This in silico optimization study led to the design and synthesis of amides 9 (IC 50 = 42.3 μM) and 10 (IC 50 = 35.2 μM), showing the most potent α-glucosidase inhibition and good antioxidative properties. A kinetic study showed that 10 acts as a mixed type inhibitor.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2019-01-01 |