Novel anticancer agents, kayeassamins C-I from the flower of Kayea assamica of Myanmar.
A CHCl3-soluble fraction of 70% EtOH extract of the flower of Kayea assamica from Myanmar exhibited 100% preferential cytotoxicity (PC(100)) against human pancreatic cancer PANC-1 cells under nutrient-deprived conditions at 1 microg/mL. Bioassay-guided fractionation and isolation afforded nine new coumarins, kayeassamins A (8), B (9), and C-I (1-7), together with nine known coumarins (10-18). The structures of these compounds were identified by extensive spectroscopic techniques as well as by comparison with published data. Absolute configuration at C-1' of 1 was established as S-configuration by the modified Mosher method. All the isolates were evaluated for their in vitro preferential cytotoxicity using novel anti-austerity strategy. Among them, the novel coumarins, kayeassamins A (8), B (9), D (2), E (3), and G (5) exhibited the most potent preferential cytotoxicity (PC(100) 1 microM) in a concentration- and time-dependent manner and induced apoptosis-like morphological changes of PANC-1 cells within 24 h of treatment. Based on the observed cytotoxicity, structure-activity relationships have been established.
Win
Nwet Nwet
NN
Institute of Natural Medicine, University of Toyama, 2630-Sugitani, Toyama 930-0194, Japan.
Awale
Suresh
S
Esumi
Hiroyasu
H
Tezuka
Yasuhiro
Y
Kadota
Shigetoshi
S
D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D001681:Biological Assay; D045744:Cell Line, Tumor; D003374:Coumarins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D002052:Myanmar; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D010936:Plant Extracts / Q000737:chemistry*; D010946:Plants, Medicinal / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013997:Time Factors; D018675:Toxicity Tests
D000972:Antineoplastic Agents, Phytogenic; D003374:Coumarins; D010936:Plant Extracts