title: Coumarin derivatives from Ainsliaea fragrans and their anticoagulant activity.
abstract: Coumarin derivatives are an important class of C6-C3 plant metabolites that show a variety of bioactivities. Currently, most clinical anticoagulant agents are coumarins, such as warfarin, dicoumarol and acenocoumarol, and patients taking these drugs must be monitored for adverse reactions. In a search for safe and effective anticoagulant compounds from Chinese herbal medicine, a screening procedure on the whole plant of Ainsliaea fragrans was performed. The phytochemical investigation of this plant afforded five new coumarin derivatives, including a pair of natural 4-hydroxycoumarin enantiomers (1), a pair of coumarin enantiomers with a rare polycyclic pyrano[3-2c] carbon skeleton (2) and a 7-hydroxycoumarin derivative (3), together with 5 known biogenetically related compounds (4-8). Enantioseparation of 1 and 2 produced optically pure compounds 1a, 1b, 2a and 2b. The absolute configurations of the new compounds were confirmed by single-crystal X-ray diffraction analysis. In addition, we evaluated the anticoagulant activity of all isolates via activated partial thromboplastin time (APTT), thrombin time (TT) and prothrombin time (PT) assays in vitro and in vivo. Of note, compound 3 displayed potent anticoagulant activity and no significant hepatic or renal toxicity, which could make it a promising agent for further preclinical evaluation for preventing abnormal blood clotting.
authors: Puai Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China.
authors: Liang
authors: L
authors: Lei
authors: Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China.
authors: Yong-bo
authors: YB
authors: Xue
authors: Puai Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China.
authors: Zhong
authors: Z
authors: Liu
authors: Puai Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China.
authors: Si-si
authors: SS
authors: Peng
authors: Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China.
authors: Yan
authors: Y
authors: He
authors: Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China.
authors: Yang
authors: Y
authors: Zhang
authors: Puai Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China.
authors: Rong
authors: R
authors: Fang
authors: Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China.
authors: Jian-ping
authors: JP
authors: Wang
authors: Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China.
authors: Zeng-wei
authors: ZW
authors: Luo
authors: Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China.
authors: Guang-min
authors: GM
authors: Yao
authors: Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China.
authors: Jin-wen
authors: JW
authors: Zhang
authors: Department of Pharmacy, Wuhan First Hospital, Wuhan 430022, Hubei, People's Republic of China.
authors: Geng
authors: G
authors: Zhang
authors: Puai Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China.
authors: Hong-ping
authors: HP
authors: Song
authors: Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China.
authors: Yong-hui
authors: YH
authors: Zhang
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D019659:Asteraceae / Q000737:chemistry*; D001777:Blood Coagulation / Q000187:drug effects; D066241:Carbon-13 Magnetic Resonance Spectroscopy; D002942:Circular Dichroism; D003374:Coumarins / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D006801:Humans; D066244:Proton Magnetic Resonance Spectroscopy; D017208:Rats, Wistar; D013237:Stereoisomerism
chemical_list: D000925:Anticoagulants; D003374:Coumarins