title: Biotransfomation of cyperenoic acid by Cunninghamella elegans AS 3.2028 and the potent anti-angiogenic activities of its metabolites.
abstract: Cyperenoic acid (1) is one of the major sesquiterpenes isolated from Croton crassifolius, which exhibited potent anti-angiogenic activity. Traditional structural modification of 1 is difficult to perform by chemical technology due to the remarkable stability of the patchoulane skeleton. In order to overcome chemical synthesis difficulties and obtain structurally diverse derivations, microbial transformation of 1 by using Cunninghamella elegans AS 3.2028 was studied for the first time. Five new hydroxylated products 2-6 were obtained. Furthermore, cytotoxicity and anti-angiogenic activities of all the biotransformation products were evaluated by MTT assay and ELISA in HepG2 and MCF-7 cells. These results indicated that hydroxylated modification products 2-4 significantly inhibited VEGF release, which suggest the potential use of hydroxylated modification products for cancer therapy.
authors.affiliation: School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Natural Products Chemistry, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Jin-Long
authors.initials: JL
authors.lastname: Tian
authors.affiliation: School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Jing-Shuai
authors.initials: JS
authors.lastname: Wu
authors.affiliation: Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Tie-Min
authors.initials: TM
authors.lastname: Sun
authors.affiliation: School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Zhou
authors.affiliation: Department of Natural Products Chemistry, Shenyang Pharmaceutical University, Shenyang 110016, China; Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: songsj99@163.com.
authors.forename: Shao-Jiang
authors.initials: SJ
authors.lastname: Song
authors.affiliation: School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: yousong206@aliyun.com.
authors.forename: Song
authors.initials: S
authors.lastname: You
mesh_terms: D020533:Angiogenesis Inhibitors / Q000378:metabolism*; D001711:Biotransformation; D029802:Croton / Q000737:chemistry*; D020093:Cunninghamella / Q000378:metabolism*; D056945:Hep G2 Cells; D006801:Humans; D061986:MCF-7 Cells; D018517:Plant Roots / Q000737:chemistry; D012717:Sesquiterpenes / Q000302:isolation & purification / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D012717:Sesquiterpenes; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C519558:cyperenoic acid
keywords: Anti-angiogenic activity; Biotransfomation; Cunninghamella elegans 3.2028; Cyperenoic acid; Cytotoxicity assay