Laetiporus sulphureus mushroom culture − source of secondary metabolites, and as a catalyst for biotransformation of breast cancer drug exemestane

Abstract

Certain mushrooms are used as low-calorie food supplements due to their excellent taste, and presence of a variety of essential vitamins, minerals and secondary metabolites. Some of them have therapeutic significance, and used in traditional medicines. Mushrooms cells can also be used as biocatalysts for the derivatization of organic compounds. During the current study, 3β-hydroxy-24-methylenelanost-8-en-21-oic acid (1) was isolated from Laetiporus sulphureus (Bull.) Murrill. The cell culture of the same mushroom was used for the biotransformation of breast cancer drug, exemestane (2) into a new analogue, 18-hydroxy-6-methylene-androsta-1,4-diene-3,17-dione (3). Compounds 1, and 3 were purified by using various chromatographic techniques, and their structures were determined with the help of 1D- and 2D-NMR, HREI-MS, and IR spectroscopic techniques. Since compound 1 also has a steroidal skeleton (like aromatase inhibiting drug exemestane (2)), the metabolite 1 was also evaluated for its aromatase inhibitory potential, along with a new transformed product 3. Aromatase plays a crucial role in estrogen biosynthesis, and therefore its inhibition is a key approach for the treatment of estrogen receptor-positive (ER+) breast cancers. Compounds 1 and 3 demonstrated a significant aromatase inhibition, with IC₅₀ values of 590 ± 0.03 nM and 337.5 ± 0.01 nM, respectively, relative to exemestane’s IC₅₀ of 210.0 ± 0.16 nM. Furthermore, in silico studies predicted that these inhibitors 1–3 were able to occupy the active site and interacted with catalytically important residues of the enzyme. While molecular dynamic simulation predicted the stability of aromatase- ligand complexes. The studies identified that metabolites 1 and 3 can serve as drug candidate after further development.