PTP1B Inhibitory Secondary Metabolites from Marine-Derived Fungal Strains Penicillium spp. and Eurotium sp.

Abstract

The selective inhibition of PTP1B has been widely recognized as a potential drug target for the treatment of type 2 diabetes and obesity. In the course of screening for PTP1B inhibitory fungal metabolites, the organic extracts of several fungal species isolated from marine environments were found to exhibit significant inhibitory effects, and the bioassay-guided investigation of these extracts resulted in the isolation of fructigenine A (1), cyclopenol (2), echinulin (3), flavoglaucin (4), and viridicatol (5). The structures of these compounds were determined mainly by analysis of NMR and MS data. These compounds inhibited PTP1B activity with 50% inhibitory concentration values of 10.7, 30.0, 29.4, 13.4, and 64.0 micrometer, respectively. Furthermore, the kinetic analysis of PTP1B inhibition by compounds 1 and 5 suggested that compound 1 inhibited PTP1B activity in a noncompetitive manner, whereas compound 5 inhibited PTP1B activity in a competitive manner.

Statistical Research on the Bioactivity of New Marine Natural Products Discovered during the 28 Years from 1985 to 2012

“…The first improvement is about methods of bioactivity-guided separation and purification of marine secondary metabolites, which combine the discovery of new compounds with bioactivity assays [ 59 ]. These improvements in technology are dependent upon the automation in NMR and mass spectroscopy (MS), which also allow the study of the functions of new compounds extracted from marine organisms’ secondary metabolites [ 60 , 61 , 62 ]. Second, for the discovery of new lead compounds for drug development, empirical cell-based screening for cytotoxicity has evolved to a more mechanistic approach that targets specific molecular lesions though there are still shortcomings [ 63 ].…”

Marine Pharmacology in 2012–2013: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti-Inflammatory, Antiprotozoal, Antituberculosis, and Antiviral Activities; Affecting the Immune and Nervous Systems, and Other Miscellaneous Mechanisms of Action

“…bisacetylenic alcohol ( 191 ) [184]; conicasterol E ( 192 ) [185]; 6”-debromohamacanthin A ( 193 ) [186]; dieckol ( 194 ) [187]; fructigenine A ( 195 ) [188]; geoditin A ( 196 ) [189]; gorgosterol ( 197 ) [190]; gracilioether B ( 198 ) [191]; gracilioether K ( 199 ) [192]; herdmanine K ( 200 ) [193]; hyrtioreticulin A ( 201 ) [194]; new Kunitz-type protease inhibitor InHVJ ( 202 ) [195]; jaspamide ( 203 ) [196]; latonduine A ( 204 ) [197]; leucettine L41 ( 205 ) [169]; manzamine A ( 206 ) [198]; nahuoic acid A ( 207 ) [199]; namalide ( 208 ) [200]; ningalins C and D ( 209 , 210 ) [201]; octaphlorethol A ( 114 ) [120]; petrosaspongiolide M ( 211 ) [202]; petrosiol A ( 212 ) [203]; phidianidine A ( 213 ) [204]; Poly-APS ( 214 ) [205]; Pseudoceratina sp. dibromotyrosine ( 215 ) [206]; pseudopterosin A ( 216 ) [207]; sargachromanol G ( 217 ) [208]; S. graminifolium polysaccharide ( 218 ) [209]; S. patens phloroglucinol ( 219 ) [210]; S. xiamenensis benzopyran ( 220 ) [211]; theonellasterol ( 221 ) [212]; toluquinol ( 222 ) [213]; and U. lactuca fatty acid ( 223 ) [214].…”

Metabolic Disorder in Chronic Obstructive Pulmonary Disease (COPD) Patients: Towards a Personalized Approach Using Marine Drug Derivatives

“…Table 2 reports new drugs and drug derivatives obtained by different marine organisms proposed in anti-obesity treatment [62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94]. …”