New α-glucosidase inhibitors from marine algae-derived Streptomyces sp. OUCMDZ-3434

Diabetes mellitus is a clinical syndrome caused by genetic factors and environmental factors and characterized by high levels of blood glucose. For the past few years, the incidence of diabetes increased rapidly, and the diabetes treatment has become a global health problem1. Over 85% diabetics suffer from Type-II diabetes mellitus (DM)2. DM is a chronic disease with clinical manifestation of hyperglycemia, due to the ineffective of insulin that controls the level of blood glucose. α-Glucosidase inhibitors, such as acarbose, voglibose and miglitol, could retard the uptake of dietary carbohydrates and have achieved significant therapeutic effect in clinical application3. However, most of these products have side effects such as flatulence, nausea, vomiting and diarrhea4. Therefore, more secure and efficient inhibitors are the urgent demand for the treatment of diabetes. Marine is believed to be a natural treasure house for medicine, and natural products of marine microbial origin play an increasingly important role in drug diescovery5. In our ongoing search for bioactive natural products with new structures from marine microorganisms6,7,8, the EtOAc extract of the fermentation broth of Streptomyces sp. OUCMDZ-3434 associated with the marine green algae, Enteromorpha prolifera, exhibited significant α-glucosidase inhibitory activity at 50 μg/mL. Chemical study lead to the identification of two new epimeric polyketides that we named wailupemycins H (1) and I (2) with an unusual carbon skeleton coupled two 6-(2-phenylnaphthalene-1-yl)pyrane-2-one nuclei into a methylene linkage, along with the known wailupemycins D (3)9, E (4),10 and G (5)10 (Fig. 1). Figure 1 Structures of compounds 1−5.