圆叶古柯茎中托烷生物碱对多药耐药性的逆转作用
Reversal of multidrug resistance by tropane alkaloids from the stems of Erythroxylum rotundifolium.
作者信息
Chávez Daniel, Cui Baoliang, Chai Hee-Byung, García Ricardo, Mejía Miliciades, Farnsworth Norman R, Cordell Geoffrey A, Pezzuto John M, Kinghorn A Douglas
机构信息
Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, 60612, USA.
出版信息
J Nat Prod. 2002 Apr;65(4):606-10. doi: 10.1021/np0104774.
Six tropane alkaloid esters were isolated from the stems of Erythroxylum rotundifolium. The structures of three new tropane esters, 7beta-hydroxy-6beta-(3,4,5-trimethoxybenzoyloxy)-3alpha-(E)-(3,4,5-trimethoxycinnamoyloxy)tropane (1), 6beta-benzoyloxy-3alpha-(Z)-(3,4,5-trimethoxycinnamoyloxy)tropane (2), and (-)-6beta-benzoyloxy-3alpha-hydroxytropane (3), were established by spectroscopic techniques. When alkaloids 1-6 were evaluated against a panel of human cancer cell lines, the new compound 6beta-benzoyloxy-3alpha-(Z)-(3,4,5-trimethoxycinnamoyloxy)tropane (2) and three known compounds, 6beta-benzoyloxy-3alpha-(3,4,5-trimethoxycinnamoyloxy)tropane (4), 6beta-benzoyloxy-3alpha-(E)-(3,4,5-trimethoxycinnamoyloxy)tropane-7beta-ol (5), and 7beta-acetoxy-6beta-benzoyloxy-3alpha-(E)-(3,4,5-trimethoxycinnamoyloxy)tropane (6), demonstrated greatest activity with multidrug-resistant oral epidermoid carcinoma (KB-V1) cells incubated in the presence of vinblastine. Thus, tropane esters of this type can reverse the multidrug-resistance phenotype, presumably by interacting with P-glycoprotein.
从圆叶古柯的茎中分离出六种托烷生物碱酯。通过光谱技术确定了三种新的托烷酯的结构，即7β-羟基-6β-(3,4,5-三甲氧基苯甲酰氧基)-3α-(E)-(3,4,5-三甲氧基肉桂酰氧基)托烷(1)、6β-苯甲酰氧基-3α-(Z)-(3,4,5-三甲氧基肉桂酰氧基)托烷(2)和(-)-6β-苯甲酰氧基-3α-羟基托烷(3)。当对生物碱1-6进行一组人类癌细胞系评估时，新化合物6β-苯甲酰氧基-3α-(Z)-(3,4,5-三甲氧基肉桂酰氧基)托烷(2)以及三种已知化合物，即6β-苯甲酰氧基-3α-(3,4,5-三甲氧基肉桂酰氧基)托烷(4)、6β-苯甲酰氧基-3α-(E)-(3,4,5-三甲氧基肉桂酰氧基)托烷-7β-醇(5)和7β-乙酰氧基-6β-苯甲酰氧基-3α-(E)-(3,4,5-三甲氧基肉桂酰氧基)托烷(6)，在长春碱存在下培养的多药耐药口腔表皮样癌(KB-V1)细胞中表现出最大活性。因此，这类托烷酯可能通过与P-糖蛋白相互作用来逆转多药耐药表型。
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