Ching-Chia Chang1, Chi-Ying Li2, Yi-Hong Tsai1, Mohamed El-Shazly3,4, Chien-Kei Wei1, Zih-Jie Yang1, Shu-Li Chen1, Chin-Chung Wu1, Yang-Chang Wu5,6, Fang-Rong Chang7,8,9,10. 1. Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, 807, Taiwan. 2. Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, 1985 Zonal Avenue, Los Angeles, CA, 90089, USA. 3. Department of Pharmacognosy, Faculty of Pharmacy, Ain-Shams University, Organization of African Unity Street, Abassia, 11566, Cairo, Egypt. 4. Department of Pharmaceutical Biology, Faculty of Pharmacy and Biotechnology, The German University in Cairo, Cairo, 11835, Egypt. 5. Graduate Institute of Integrated Medicine, China Medical University, Taichung, 404, Taiwan. 6. Chinese Medicine Research and Development Center, China Medical University Hospital, Taichung, 404, Taiwan. 7. Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, 807, Taiwan. aaronfrc@kmu.edu.tw. 8. Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung, 807, Taiwan. aaronfrc@kmu.edu.tw. 9. Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, 807, Taiwan. aaronfrc@kmu.edu.tw. 10. Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung, 804, Taiwan. aaronfrc@kmu.edu.tw.
Abstract
MAIN CONCLUSION: We discovered and identified a series of characteristic substances, including one new polyketide, epicorepoxydon B, of the important pathogenic fungus, Epicoccum sorghinum, of sorghum. The fungal extract and some isolated polyketides are sensitive to a malignant triple-negative breast cancer cell line, MDA-MB-231. Sorghum (Kaoliang) grain is an important crop with high economic value and several applications. In Taiwan, sorghum has been used in the wine industry, and "Kinmen Kaoliang Liquor" is a well-known Asian brand. Fungal contamination is one of the major threats affecting the production of sorghum grain resulting in economic losses as well as human and animal health problems. Several fungal species can infect sorghum grain and generate some toxic secondary metabolites. Epicoccum sorghinum is one of the major fungal contaminants of sorghum grains and a potent producer of mycotoxins such as tenuazonic acid (TeA). However, except for TeA, few studies focused on chemical compounds produced by this fungus. To explore the potential biological and toxic effects of E. sorghinum, a chemical investigation was carried out on the ethyl acetate extract of the fungus because it showed cytotoxic activity against a triple-negative breast cancer cell line, MDA-MB-231 (54.82% inhibition at 20 µg/mL). One new polyketide, epicorepoxydon B (1), along with six known compounds including 4,5-dihydroxy-6-(6'-methylsalicyloxy)-2-hydroxymethyl-2-cyclohexenl-one (2), epicorepoxydon A (3), 3-hydroxybenzyl alcohol (4), 6-methylsalicylic acid (5), gentisyl alcohol (6), and 6-(hydroxymethyl)benzene-1,2,4-triol (7) were obtained, and their structures were established by the interpretation of their MS and NMR spectroscopic data. The cytotoxic activity of all isolated polyketides 1-7 was evaluated, and compounds 2, 6, and 7 exhibited potent activities against A549, HepG2, and MDA-MB-231 human cancer cell lines with IC50 value ranging from 1.86 to 18.31 μM. The structure-activity relationship of the isolated compounds was proposed.
MAIN CONCLUSION: We discovered and identified a series of characteristic substances, including one new polyketide, epicorepoxydon B, of the important pathogenic fungus, Epicoccum sorghinum, of sorghum. The fungal extract and some isolated polyketides are sensitive to a malignant triple-negative breast cancer cell line, MDA-MB-231. Sorghum (Kaoliang) grain is an important crop with high economic value and several applications. In Taiwan, sorghum has been used in the wine industry, and "Kinmen Kaoliang Liquor" is a well-known Asian brand. Fungal contamination is one of the major threats affecting the production of sorghum grain resulting in economic losses as well as human and animal health problems. Several fungal species can infect sorghum grain and generate some toxic secondary metabolites. Epicoccum sorghinum is one of the major fungal contaminants of sorghum grains and a potent producer of mycotoxins such as tenuazonic acid (TeA). However, except for TeA, few studies focused on chemical compounds produced by this fungus. To explore the potential biological and toxic effects of E. sorghinum, a chemical investigation was carried out on the ethyl acetate extract of the fungus because it showed cytotoxic activity against a triple-negative breast cancer cell line, MDA-MB-231 (54.82% inhibition at 20 µg/mL). One new polyketide, epicorepoxydon B (1), along with six known compounds including 4,5-dihydroxy-6-(6'-methylsalicyloxy)-2-hydroxymethyl-2-cyclohexenl-one (2), epicorepoxydon A (3), 3-hydroxybenzyl alcohol (4), 6-methylsalicylic acid (5), gentisyl alcohol (6), and 6-(hydroxymethyl)benzene-1,2,4-triol (7) were obtained, and their structures were established by the interpretation of their MS and NMR spectroscopic data. The cytotoxic activity of all isolated polyketides 1-7 was evaluated, and compounds 2, 6, and 7 exhibited potent activities against A549, HepG2, and MDA-MB-231 human cancer cell lines with IC50 value ranging from 1.86 to 18.31 μM. The structure-activity relationship of the isolated compounds was proposed.
Authors: Harwoko Harwoko; Jungho Lee; Rudolf Hartmann; Attila Mándi; Tibor Kurtán; Werner E G Müller; Michael Feldbrügge; Rainer Kalscheuer; Elena Ancheeva; Georgios Daletos; Marian Frank; Zhen Liu; Peter Proksch Journal: Fitoterapia Date: 2020-07-31 Impact factor: 2.882