Microbial Transformation of Yakuchinone A and Cytotoxicity Evaluation of Its Metabolites

Abstract

Yakuchinone A (1) is a bioactive diarylheptanoid isolated from the dried fruits of Alpinia oxyphylla. Microbial transformation has been recognized as an efficient method to produce new biologically active derivatives from natural products. In the present study, microbial transformation of yakuchinone A was performed with the fungus Mucor hiemalis KCTC 26779, which led to the isolation of nine new metabolites (2, 3a, 3b, and 4–9). Their structures were elucidated as (3S)-oxyphyllacinol (2), (3S,7R)- and (3S,7S)-7-hydroxyoxyphyllacinol (3a and 3b), (3S)-oxyphyllacinol-4′-O-β-d-glucopyranoside (4), (3S)-4″-hydroxyoxyphyllacinol (5), (3S)-3″-hydroxyoxyphyllacinol (6), (3S)-2″-hydroxyoxyphyllacinol (7), (3S)-2″-hydroxyoxyphyllacinol-2″-O-β-d-glucopyranoside (8), and (3S)-oxyphyllacinol-3-O-β-d-glucopyranoside (9) based on the comprehensive spectroscopic analyses and the application of modified Mosher’s method. All compounds were evaluated for their cytotoxic activities against melanoma, as well as breast, lung, and colorectal cancer cell lines. Compound 9, which was O-glucosylated on the diarylheptanoid alkyl chain, exhibited the most selective cytotoxic activities against melanoma cell lines with the IC50 values ranging from 6.09 to 9.74 μM, indicating that it might be considered as a possible anti-cancer lead compound.

Curcuminoids as Anticancer Drugs: Pleiotropic Effects, Potential for Metabolic Reprogramming and Prospects for the Future

“…To mention just a few, in the search for new marine anticancer drugs, and in a context of global climate change that could affect bioresources [ 249 ], the potential of new molecules extracted from marine invertebrates that have an ability to reverse the immune-escape phenotype in metastatic tumors has just started [ 250 ]. With respect to the third question discussed above, new biologically active derivatives produced through microbial transformation of curcuminoids (diarylheptanoids) isolated from natural resources are also being studied [ 251 ].…”

Phytochemical and pharmacological properties of the genus Alpinia from 2016 to 2023

“…Among them, compound 63 showed the most selective cytotoxic activities against murine melanoma (B16F1 and B16F10) and human melanoma (A375P) cell lines (IC 50 values: 6.1-9.7 mM). 49 Terpenoid derivatives also exhibited cytotoxic activity. 3,4-Dihydrolactucin (252), a guaiane-type sesquiterpenoid, showed cytotoxicity against MDA-MB-231 and HeLa cells, with IC 50 values of 37 and 75 mg mL −1 , respectively.…”

“…28,45 Preparative scale microtransformation of yakuchinone A (4) was performed with Mucor hiemalis to study the structure-activity relationship of yakuchinone A derivatives against HT-29 cancer cells. 49 Eight new metabolites were isolated from the sample: (3S)-oxyphyllacinol (56), (3S)-7-hydroxyoxyphyllacinol (57), (3S)-2 00 -hydroxyoxyphyllacinol (58), (3S)-3 00hydroxyoxyphyllacinol ( 59), (3S)-4 00 -hydroxyoxyphyllacinol (60), Name No. Name 1,7-Diphenylheptan-3-one 25 38 (5S)-5-Methoxy-1,7-diphenylhepta-6-en-3-one 22 7-(4 00 -Hydroxy-3 00 -methoxyphenyl)-1-phenylheptan-3-one 41 39 trans-(4R,5S)-Epoxy-1,7-diphenylheptan-3-one 45 7-(4 00 -Actetoxy-3 00 -methoxy phenyl)-1-phenylheptan-3-one 41 40 1,7-Diphenylhept-5-en-3-one 45 Yakuchinone A 49,50 41 (4E,6E)-7-(4 00 -Hydroxy-3 00 -methoxyphenyl)-1-phenylhepta-4,6-dien-3-one 45 5 0 -Hydroxyyakuchinone A 50 42 (3S,5S,6S)-1-(4 0 -Hydroxy-3 0 -methoxyphenyl)-7phenylheptane-3,5,6-triol 25 1,7-Diphenylheptane-3,5-dione 25 43 1,7-Diphenylheptane-3,5-diol 25,68 1-(3 0 ,4 0 -Dihydroxyphenyl)-7-phenylheptane-3,5-dione 25 44 1-(4 0 -Hydroxyphenyl)-7-phenylheptane-3,5-diol 25 1-(4 0 -Hydroxy-3 0 -methoxyphenyl)-7-phenylheptane-3,5dione 25…”