Alpha-Glucosidase- and Lipase-Inhibitory Phenalenones from a New Species of <i>Pseudolophiostoma</i> Originating from Thailand
Allan Patrick G. Macabeo,
Luis Agustin E. Pilapil,
Katherine Yasmin M. Garcia,
Mark Tristan J. Quimque,
Chayanard Phukhamsakda,
Allaine Jean C. Cruz,
Kevin D. Hyde,
Marc Stadler
Affiliations
Allan Patrick G. Macabeo
Laboratory for Organic Reactivity, Discovery and Synthesis (LORDS), Research Center for the Natural and Applied Sciences, University of Santo Tomas, Espana Blvd., Manila 1015, Philippines
Luis Agustin E. Pilapil
Laboratory for Organic Reactivity, Discovery and Synthesis (LORDS), Research Center for the Natural and Applied Sciences, University of Santo Tomas, Espana Blvd., Manila 1015, Philippines
Katherine Yasmin M. Garcia
Laboratory for Organic Reactivity, Discovery and Synthesis (LORDS), Research Center for the Natural and Applied Sciences, University of Santo Tomas, Espana Blvd., Manila 1015, Philippines
Mark Tristan J. Quimque
Laboratory for Organic Reactivity, Discovery and Synthesis (LORDS), Research Center for the Natural and Applied Sciences, University of Santo Tomas, Espana Blvd., Manila 1015, Philippines
Chayanard Phukhamsakda
Center of Excellence in Fungal Research, Mae Fah Luang University, Chiang Rai 57100, Thailand
Allaine Jean C. Cruz
Laboratory for Organic Reactivity, Discovery and Synthesis (LORDS), Research Center for the Natural and Applied Sciences, University of Santo Tomas, Espana Blvd., Manila 1015, Philippines
Kevin D. Hyde
Center of Excellence in Fungal Research, Mae Fah Luang University, Chiang Rai 57100, Thailand
Marc Stadler
Department of Microbial Drugs, Helmholtz Centre for Infection Research and German Centre for Infection Research (DZIF), partner site Hannover/Braunschweig, Inhoffenstrasse 7, 38124 Braunschweig, Germany
The alpha-glucosidase- and lipase-inhibitory activities of three phenalenones (1−3) and one phenylpropanoid (4) from the ethyl acetate extracts of a Pseudolophiosptoma sp. are described. They represent the first secondary metabolites reported from the genus Pseudolophiostoma. Scleroderolide (1) and sclerodione (2) exhibited potent α-glucosidase- and porcine-lipase-inhibitory activity during primary screening, with better IC50 values compared to the positive controls, N-deoxynojirimycin and orlistat. In silico techniques were employed to validate the probable biological targets and elucidate the mechanism of actions of phenalenones 1 and 2. Both compounds exhibited strong binding affinities to both alpha-glucosidase and porcine lipase through H-bonding and π−π interactions. Interestingly, favorable in silico ADME (absorption, distribution, metabolism, and excretion) properties such as gastrointestinal absorption were also predicted using software.
