1. Synthesis of Rosmarinic Acid Amides as Antioxidative and Hypoglycemic Agents
- Author
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Antonio Rescifina, Sergio Rosselli, Giuseppe Floresta, Corrado Tringali, Vera Muccilli, Nunzio Cardullo, Giorgia Catinella, Maurizio Bruno, Cardullo N., Catinella G., Floresta G., Muccilli V., Rosselli S., Rescifina A., Bruno M., and Tringali C.
- Subjects
Drug ,Antioxidant ,DPPH ,Proton Magnetic Resonance Spectroscopy ,media_common.quotation_subject ,medicine.medical_treatment ,Pharmaceutical Science ,Oxidative phosphorylation ,Pharmacology ,Depsides ,01 natural sciences ,Antioxidants ,Analytical Chemistry ,chemistry.chemical_compound ,Drug Discovery ,medicine ,Hypoglycemic Agents ,Settore BIO/15 - Biologia Farmaceutica ,Carbon-13 Magnetic Resonance Spectroscopy ,IC50 ,media_common ,Acarbose ,010405 organic chemistry ,diabetes mellitu ,Drug Discovery3003 Pharmaceutical Science ,Rosmarinic acid ,Organic Chemistry ,Settore CHIM/06 - Chimica Organica ,Complementary and Alternative Medicine2708 Dermatology ,Amides ,amide ,0104 chemical sciences ,010404 medicinal & biomolecular chemistry ,Complementary and alternative medicine ,chemistry ,Cinnamates ,Polyphenol ,Molecular Medicine ,3003 ,α-glucosidase ,medicine.drug - Abstract
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.
- Published
- 2019