Synthesis of Rosmarinic Acid Amides as Antioxidative and Hypoglycemic Agents

Journal of Natural Products
Nunzio CardulloCorrado Tringali

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 (IC50 = 42.3 μM) and 10 (IC50 = 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.

References

Aug 1, 1996·Journal of Computer-aided Molecular Design·G M MorrisA J Olson
Dec 17, 2002·Phytochemistry·Maike Petersen, Monique S J Simmonds
Dec 28, 2002·Journal of Agricultural and Food Chemistry·Toshio NiwaToshihiko Osawa
Jun 9, 2005·Clinica Chimica Acta; International Journal of Clinical Chemistry·Annunziata LapollaPietro Traldi
Aug 28, 2007·The American Journal of Cardiology·James H O'Keefe, David S H Bell
Jan 5, 2008·Current Diabetes Reports·Ariane Godbout, Jean-Louis Chiasson
Feb 10, 2009·Current Topics in Medicinal Chemistry·Wataru HakamataTadatake Oku
Nov 27, 2009·Journal of Agricultural and Food Chemistry·Yan Qin LiFang Shan
Sep 18, 2010·Journal of the American College of Nutrition·Anoop MisraLokesh Khurana
Jan 29, 2013·Daru : Journal of Faculty of Pharmacy, Tehran University of Medical Sciences·Fahimeh Moradi-AfrapoliNarguess Yassa
Feb 13, 2013·Journal of Natural Products·Rachel MataIsabel Rivero-Cruz
Mar 2, 2013·Current Pharmaceutical Design·Teresa Vanessa FiorentinoFranco Folli
May 9, 2014·Chembiochem : a European Journal of Chemical Biology·Philippe Compain, Anne Bodlenner
Feb 9, 2016·Critical Reviews in Food Science and Nutrition·Hui Teng, Lei Chen
Aug 10, 2016·Journal of Natural Products·Nunzio CardulloCorrado Tringali
Dec 21, 2016·Journal of Natural Products·Sonia Escandón-RiveraRachel Mata
May 13, 2017·Journal of Natural Products·Luana PulvirentiCorrado Tringali
Dec 9, 2017·Nature Reviews. Endocrinology·Yan ZhengFrank B Hu
Feb 18, 2018·European Journal of Medicinal Chemistry·Loredana SalernoValeria Pittalà
May 23, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Khaled F GreishValeria Pittalà

❮ Previous
Next ❯

Citations

Feb 13, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Nunzio CardulloCorrado Tringali
Jul 28, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Nunzio CardulloCorrado Tringali
Mar 2, 2021·Journal of Natural Products·Nunzio CardulloCorrado Tringali

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.