title: Involucratusins A-H: Unusual Cadinane Dimers from Stahlianthus involucratus with Multidrug Resistance Reversal Activity.
abstract: Three novel cadinane dimers, involucratusins A-C (1-3), five unique nor-cadinane-dimers, involucratusins D-H (4-8), together with a known compound (9) were isolated from the rhizomes of Stahlianthus involucratus. Their challenging structures and absolute configurations were determined by spectroscopic data, CD experimentation, chemical conversions and single-crystal X-ray diffraction. Compounds 1-3 are unusual cadinane dimers with new connection and novel cores. Compound 4 is a unique nor-cadinane-dimer, and 5 and 6 are two pairs of hemiketal racemates with novel dinor-cadinane-dimer backbone. Compounds 7 and 8 represent unusual dodecanor-cadinane-dimer and tetradecanor-cadinane-dimer carbon skeletons, respectively. The possible biogenetic pathways of 1-8 were proposed, involving nucleophilic addition, SN2 nucleophilic displacement, [3 + 3] benzannulation, oxidative cleavage, decarboxylation, and oxidative phenol coupling reactions. Multidrug resistance (MDR) reversal activity assay of the isolates were evaluated in doxorubicin-resistant human breast cancer cells (MCF-7/DOX). The combined use of these novel cadinane dimers at a concentration of 10 μM increased the cytotoxicity of doxorubicin by 2.2-5.8-fold. It is the first report about the MDR reversal activity of cadinane dimers.
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, People's Republic of China.
authors.forename: Qiang-Ming
authors.initials: QM
authors.lastname: Li
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, People's Republic of China.
authors.forename: Jian-Guang
authors.initials: JG
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, People's Republic of China.
authors.forename: Rui-Zhi
authors.initials: RZ
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, People's Republic of China.
authors.forename: Xiao-Bing
authors.initials: XB
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, People's Republic of China.
authors.forename: Ming-Hua
authors.initials: MH
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, People's Republic of China.
authors.forename: Ling-Yi
authors.initials: LY
authors.lastname: Kong
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D019684:Magnoliopsida / Q000737:chemistry*; D000081223:Polycyclic Sesquiterpenes; D027343:Rhizome / Q000737:chemistry*; D012717:Sesquiterpenes / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D000081223:Polycyclic Sesquiterpenes; D012717:Sesquiterpenes; C508039:cadinane; D004317:Doxorubicin