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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.

Tropane alkaloids are molecules with a strong biological activity, which are mainly produced by the members offamily Solanaceae, but also found inother plant families (Convolvulaceae, Brasicaceae, Erythroxylaceae andEuphorbiaceae).1 More than 20 active pharmaceutical substances containingthetropane moiety have been industrially produced and applied as mydriatics, antiemetics, antispasmodics, anesthetics and bronchodilators.Nearly all of them are based on the Scopolamine structure.2 In recent years, several researchers aimed their work to the use of supramolecular systems for the inclusion of organic species, such as complex systems based on cyclodextrines or calixarenes.3They have attracted increasing interest during the past years, due to their adsorption or controlled release abilities towards various organic molecules. An interesting new class of material is calixarene-cyclodextrinenanosponges, which consists of a polymeric network of host co-monomer units crosslinked by triazole units and exhibiting cavities and nanopores in the range of nanometers. The present research work was designed to produce many derivatives of scopolamine, keeping in view their biological activity and comparing them with current tropane pharmaceuticals. Moreover, the research aims to study pharmacokinetics of these derivatives with functionalized calixarene-cyclodextrine polymers as promising drug carriers.