Molecular docking and in vitro anticancer evaluation of potential compounds derived from Indonesian sponge Agelas nakamurai.

Objective: This study evaluated the anticancer activity (in silico and in vitro) of compounds derived from the Agelas nakamurai collected from Indonesian waters against the triple-negative breast cancer cancer cell line MDA-MB-231.

Background: The marine sponge genus Agelas is known to biosynthesize a variety of secondary metabolites with anticancer properties.

Materials and methods: The compounds were separated using open column and preparative high-performance liquid chromatography. The liquid chromatography-mass spectrometry/mass spectrometry and nuclear magnetic resonance data were used to characterize compounds. Antiproliferation test of isolated compounds was conducted against the MDA-MB-231 cell line. Meanwhile p53 MDM2 protein [PDB]: 4OQ3, and Estimated Glomerular Filtration Rate (EGFR) protein (PDB: 1T46) were utilized for molecular docking and dynamic (MD) analysis.

Results: LC-MS data of fraction F7 indicated the presence of agelasine D, ageloxime D, agelanin B, and midpacamide. Further purification of fraction F7 led to the agelasin D and ageloxime D. Both compounds inhibited the MDA-MB-231 cell line with IC50 values of 7.09 and 171.07 µM, respectively. The docking results showed that the binding affinity of agelasine D and ageloxime D to 4OQ3 and 1T46 were close, with scores ranging from -7.3 to -9.0 kcal/mol. MD simulation within 100 ns indicated agelasin D and ageloxime-D make stable binding to the targeted proteins with root-mean-square deviation <2Å.

Conclusions: The isolated compounds from A. nakamurai showed potent against the MDA-MB-231 cell line, based on in vitro and in silico analysis. The MD data supported that the compounds effectively inhibit cancer growth through the MDM2 or EGFR pathways. Thus, this study suggested further in vitro mechanism of action analysis.