title: Purpurogemutantin and purpurogemutantidin, new drimenyl cyclohexenone derivatives produced by a mutant obtained by diethyl sulfate mutagenesis of a marine-derived Penicillium purpurogenum G59.
abstract: Two new drimenyl cyclohexenone derivatives, named purpurogemutantin (1) and purpurogemutantidin (2), and the known macrophorin A (3) were isolated from a bioactive mutant BD-1-6 obtained by random diethyl sulfate (DES) mutagenesis of a marine-derived Penicillium purpurogenum G59. Structures and absolute configurations of 1 and 2 were determined by extensive spectroscopic methods, especially 2D NMR and electronic circular dichroism (ECD) analysis. Possible biosynthetic pathways for 1-3 were also proposed and discussed. Compounds 1 and 2 significantly inhibited human cancer K562, HL-60, HeLa, BGC-823 and MCF-7 cells, and compound 3 also inhibited the K562 and HL-60 cells. Both bioassay and chemical analysis (HPLC, LC-ESIMS) demonstrated that the parent strain G59 did not produce 1-3, and that DES-induced mutation(s) in the mutant BD-1-6 activated some silent biosynthetic pathways in the parent strain G59, including one set for 1-3 production.
authors: Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.|Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors: Shi-Ming
authors: SM
authors: Fang
authors: Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.|Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors: Cheng-Bin
authors: CB
authors: Cui
authors: Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.
authors: Chang-Wei
authors: CW
authors: Li
authors: Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.
authors: Chang-Jing
authors: CJ
authors: Wu
authors: Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.
authors: Zhi-Jun
authors: ZJ
authors: Zhang
authors: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
authors: Li
authors: L
authors: Li
authors: Institute of Traditional Chinese Medicine & Natural Products, Jinan University, Guangzhou 510632, China.
authors: Xiao-Jun
authors: XJ
authors: Huang
authors: Institute of Traditional Chinese Medicine & Natural Products, Jinan University, Guangzhou 510632, China.
authors: Wen-Cai
authors: WC
authors: Ye
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D059001:Aquatic Organisms / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001688:Biological Products / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D045744:Cell Line, Tumor; D002942:Circular Dichroism / Q000379:methods; D004354:Drug Screening Assays, Antitumor; D018922:HL-60 Cells; D006367:HeLa Cells; D006801:Humans; D020014:K562 Cells; D061986:MCF-7 Cells; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D016296:Mutagenesis; D009154:Mutation; D010407:Penicillium / Q000737:chemistry* / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D013463:Sulfuric Acid Esters / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D001688:Biological Products; D013463:Sulfuric Acid Esters; C011612:diethyl sulfate