Database compilation and virtual screening of secondary metabolites derived from marine fungi as epidermal growth factor receptor tyrosine kinase inhibitors

Abstract

Objective: Epidermal growth factor receptor (EGFR), a transmembrane protein with cytoplasmic kinase activity, transduces growth factor signaling from the extracellular space to the cell. EGFR downstream signaling increases proliferation and reduces apoptosis. Agents that are targeted at intracellular tyrosine kinase are tyrosine kinase inhibitor small molecules, which have a mechanism of action that affects adenosine triphosphate binding to the receptor. The exploration of bioactive compounds from marine materials, including marine fungi, has become a major interest lately for anticancer treatment. Methods: In this research, a database was created and in silico screening was conducted using AutoDock and Vina to obtain potential marine fungi bioactive compounds as EGFR-tyrosine kinase (EGFR-TK) inhibitors, which act as antiproliferative agents on tumor cell growth. Results: This research has concluded that the three marine fungi compounds with the lowest binding free energy, FU0015, FU0051, and FU0202, have great potential as inhibitors of EGFR-TK. Conclusions: Three active compounds were identified as inhibitors of EGFR-TK, which were Fiscalin A, derived from Neosartorya paulistensis KUFC 7897 (FU0015); Aspergiolide B, derived from Aspergillus flavus (FU0051); and Sporothrix A, derived from Sporothrix sp. (FU0202).