Abstract
The biotransformation of the front-line antimalarial drug, artemisinin (1) by the filamentous fungus Aspergillus flavus MTCC-9167 was investigated. Incubation of compound 1 with A. flavus afforded a new hydroxy derivative (2) along with three known metabolites (3-5). The new compound was characterized as 14-hydroxydeoxyartemisinin (2) by extensive spectroscopic data analysis (IR, 1H and 13C NMR, HSQC, HMBC, COSY, NOESY, and HR-ESIMS). The known metabolites were identified as deoxyartemisinin (3), artemisinin G (4), and 4α-hydroxydeoxyartemisinin (5). This is the first report of hydroxylation of a secondary methyl of artemisinin at C-14 by the fungus A. flavus, which is synthetically not accessible. In addition, these compounds were evaluated for their in vitro antiplasmodial activity. Artemisinin G (4) exhibited IC50 values in the submicromolar range, which was better than those of the nonperoxidic metabolites.
References
Aug 20, 1976·Science·W Trager, J B Jensen
Sep 1, 1989·Journal of Natural Products·R J Roth, N Acton
Mar 1, 1989·Journal of Natural Products·I S LeeC D Hufford
Sep 1, 1987·Journal of Natural Products·S A ElmarakbyC D Hufford
Nov 26, 2002·Journal of Natural Products·Ji-Xun ZhanDe-An Guo
Jan 22, 2004·Applied Microbiology and Biotechnology·I A ParshikovJ S Williamson
Apr 9, 2004·Proceedings of the National Academy of Sciences of the United States of America·Puran S Sijwali, Philip J Rosenthal
Jun 26, 2004·Journal of Natural Products·Wen-Yuh TengChien-Chih Chen
Jan 4, 2006·Journal of Industrial Microbiology & Biotechnology·Igor A ParshikovJohn S Williamson
Jan 26, 2006·Bioorganic & Medicinal Chemistry Letters·Ji-Hua LiuYi-Jun Chen
Jun 1, 1992·Planta medica·Z X WeiY Li
Nov 17, 2009·Bioorganic & Medicinal Chemistry Letters·Abhishek GoswamiMadhunika Sharma
Feb 10, 2012·Journal of Natural Products·M Gowri PonnapalliV Raju Tuniki
Apr 10, 2012·Biotechnology Advances·Igor A ParshikovJohn B Sutherland
Nov 6, 2012·Journal of the American Chemical Society·Kaidong ZhangRudi Fasan
Feb 7, 2013·Progress in Medicinal Chemistry·Félix CalderónFrancisco-Javier Gamo
Sep 12, 2013·PloS One·Rajesh PrasadPuran Singh Sijwali
Sep 4, 2014·Phytochemistry·Rashmi GaurRajendra Singh Bhakuni
Dec 18, 2014·Natural Product Research·Madhu Babu SuraMangala Gowri Ponnapalli
Aug 9, 2016·Natural Product Research·Mangala Gowri PonnapalliJeelani Basha Shaik
Citations
Jul 24, 2020·Chemical Society Reviews·Suman ChakrabartyAlison R H Narayan
Jan 19, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Yue MaLan Yang
Jan 22, 2021·Organic Letters·Zi-Liang TangJin-Heng Li
Mar 31, 2021·Journal of Asian Natural Products Research·Nurul Iman AminudinZaima Azira Zainal Abidin