Mycophenolic Acid Derivatives from Vietnamese Marine Sponge-derived Penicillium sp. 1901NT-2.53.1 Strain and their Antiproliferative Activity

Abstract

Background Marine sponges and sponge-associated fungi are rich sources of bioactive compounds with pharmacological potential. However, the secondary metabolites of Vietnamese marine sponge-derived fungi have been poorly studied. Objective The aim of this study was to investigate the low-molecular-weight compounds in the extract of Penicillium sp. 1901NT-2.53.1 fungus isolated from the Vietnamese marine sponge Cinachyrella sp., and the antiproliferative activity of the isolated compounds. Methods The structures of isolated compounds were elucidated using spectroscopic methods. The cell viability effects of the compounds were evaluated using MTT assay. Molecular docking was performed using SwissDock. Results UPLC-MS data suggested the presence of beauvericin, citreorosein, benzopyran and chlorotetracycline derivatives, 2-chloro-1,3,8-trihydroxy-6-(hydroxymethyl)anthracene-9,10- dione and ergosterol peroxide in the fungal extract. Chromatographic separation of the extract resulted in the isolation of three derivatives of mycophenolic acid (MPA), namely penicacids G and K and 4-hydroxy-MPA. Penicacid K was isolated from a natural source for the first time. Penicacid G inhibited the viability of human normal HaCaT keratinocytes with IC50 of 88.3 μM and 72.9 μM for 24 h and 48 h of treatment, respectively. Moreover, penicacid G arrested the proliferation of HaCaT keratinocytes. Both penicacids K and G can interact with the active site of IMPDH2, similar to other derivatives of MPA; however, the differences in their structures are important. Conclusion Due to the selective action on cancer cells and good druggability, penicacid G may be interesting as an antiproliferative anticancer compound.