Molyneux R J, Pan Y T, Goldmann A, Tepfer D A, Elbein A D
Western Regional Research Center, United States Department of Agriculture, Albany, California 94710.
Arch Biochem Biophys. 1993 Jul;304(1):81-8. doi: 10.1006/abbi.1993.1324.
The alkaloid extract from roots of naturally growing Convolvulus arvensis, purified by ion-exchange chromatography, showed significant inhibitory activity toward beta-glucosidase and alpha-galactosidase. The demonstrated occurrence of polyhydroxy-nortropane alkaloids, the calystegins, in C. arvensis and their structural similarity to known polyhydroxy alkaloid glycosidase inhibitors, suggested that these might be responsible for the observed activity. Pure calystegins, isolated from transformed root cultures of the related plant species Calystegia sepium, were tested for glycosidase inhibitory activity. The purity of the alkaloids was established by gas chromatography and their identity confirmed by their mass spectrometric fragmentation patterns. The trihydroxy alkaloid, calystegin A3, was a moderately good inhibitor of beta-glucosidase (Ki = 4.3 x 10(-5) M) and a weak inhibitor of alpha-galactosidase (Ki = 1.9 x 10(-4) M). An increased level of hydroxylation, as in the tetrahydroxy calystegins B, consisting of 27% calystegin B1 and 73% calystegin B2, resulted in greatly enhanced inhibitory activity. The calystegins B were potent inhibitors of beta-glucosidase (Ki = 3 x 10(-6) M) and alpha-galactosidase (Ki = 7 x 10(-6) M). These levels of activity are comparable with those of the polyhydroxy indolizidine alkaloids castanospermine and swainsonine toward alpha-glucosidase and alpha-mannosidase, respectively, and of the polyhydroxy pyrrolizidine alkaloid australine toward alpha-glucosidase. The calystegins therefore compose a new structural class of polyhydroxy alkaloids, the nortropanes, possessing potent glycosidase inhibitory properties.
从自然生长的田旋花根部提取的生物碱提取物，经离子交换色谱法纯化后，对β-葡萄糖苷酶和α-半乳糖苷酶显示出显著的抑制活性。已证实田旋花中存在多羟基降托烷生物碱（即旋花茄苷），且它们与已知的多羟基生物碱糖苷酶抑制剂在结构上相似，这表明这些生物碱可能是观察到的活性的原因。从相关植物物种打碗花的转化根培养物中分离出的纯旋花茄苷，对其糖苷酶抑制活性进行了测试。通过气相色谱法确定生物碱的纯度，并通过其质谱裂解模式确认其身份。三羟基生物碱旋花茄苷A3是β-葡萄糖苷酶的中度良好抑制剂（Ki = 4.3×10⁻⁵ M），是α-半乳糖苷酶的弱抑制剂（Ki = 1.9×10⁻⁴ M）。如四羟基旋花茄苷B（由27%的旋花茄苷B1和73%的旋花茄苷B2组成）中羟基化水平的提高，导致抑制活性大大增强。旋花茄苷B是β-葡萄糖苷酶（Ki = 3×10⁻⁶ M）和α-半乳糖苷酶（Ki = 7×10⁻⁶ M）的强效抑制剂。这些活性水平分别与多羟基吲哚里西啶生物碱栗精胺和苦马豆素对α-葡萄糖苷酶和α-甘露糖苷酶的活性水平相当，以及与多羟基吡咯里西啶生物碱澳洲茄碱对α-葡萄糖苷酶的活性水平相当。因此，旋花茄苷构成了一类新的具有强效糖苷酶抑制特性的多羟基生物碱结构类型，即降托烷类生物碱。
