Novel antihyperglycemic terpenoid-quinones from Pycnanthus angolensis.

Two new compounds, pycnanthuquinone A (1) and pycnanthuquinone B (2), were isolated from leaves and stems of the African plant, Pycnanthus angolensis (Welw.) Warb (Myristicaceae), by bioassay-guided fractionation of an ethanolic extract using a diabetic mouse model. Pycnanthuquinones A and B are the first representatives of a novel terpenoid-type quinone skeleton, and both compounds possess significant antihyperglycemic activity.

Antihyperglycemic acetylenic glucosides from Bidens pilosa.

In vivo bioassay-guided fractionation of the aqueous alcohol extract of the aerial parts of Bidens pilosa Sch. Bip. var. radiata (Asteraceae) using C57 BL/Ks-db/db mice as a model for type 2 diabetes, yielded two known polyacetylenic glucosides, identified as 2-beta-D-glucopyranosyloxy-1-hydroxy-5(E)-tridecene-7,9,11-+ ++triyne (1) and 3-beta-D-glucopyranosyloxy-1-hydroxy-6(E)-tetradecene-8,10,1 2-triyne (2). A 3:2 mixture of compounds 1 and 2 effected a significant drop in blood glucose.

Antihyperglycemic activity of Teramnus labialis (Fabaceae).

In vivo bioassay-guided fractionation of the aqueous alcohol extract of the aerial parts of Teramnus labialis (Roxb.) Benth. (Fabaceae), using C57BL/Ks-db/db mice as a model for type 2 diabetes, yielded an active fraction containing a mixture of coumarins. The major coumarin present in the active fraction was identified as fraxidin.

Novel terpenoid-type quinones isolated from Pycnanthus angolensis of potential utility in the treatment of type 2 diabetes.

Using an ethnomedical-based drug discovery program, two previously unknown compounds (SP-18904 and SP-18905) from Pycnanthus angolensis were isolated that lower glucose concentrations in mouse models of type 2 diabetes. SP-18904 and SP-18905 are terpenoid-type quinones that significantly lowered plasma glucose concentration (p <.05) when given orally to either ob/ob or db/db mice, both of which are hyperglycemic and hyperinsulinemic. The antihyperglycemic actions of SP-18904 and SP-18905 were associated with significant decreases in plasma insulin concentrations (p <.05), suggesting that both compounds lowered glucose by enhancing insulin-mediated glucose uptake. This was supported by the insulin suppression test in ob/ob mice. Studies in hyperglycemic, insulin-deficient mice and in vitro experiments on 3T3-L1 adipocytes further supported this conclusion. As such, these two terpenoid-type quinones represent a new class of compounds of potential use in the treatment of type 2 diabetes.

Antihyperglycemic activities of cryptolepine analogues: an ethnobotanical lead structure isolated from Cryptolepis sanguinolenta.

Cryptolepine (1) is a rare example of a natural product whose synthesis was reported prior to its isolation from nature. In the previous paper we reported the discovery of cryptolepine's antihyperglycemic properties. As part of a medicinal chemistry program designed to optimize natural product lead structures originating from our ethnobotanical and ethnomedical field research, a series of substituted and heterosubstituted cryptolepine analogues was synthesized. Antihyperglycemic activity was measured in vitro and in an NIDDM mouse model to generate the first structure-bioactivity study about the cryptolepine nucleus.

Cryptolepis sanguinolenta: an ethnobotanical approach to drug discovery and the isolation of a potentially useful new antihyperglycaemic agent.

Evidence has been published that a wide array of plant-derived active principles, representing numerous classes of chemical compounds, demonstrate activity consistent with their possible use in the treatment of patients with Type 2 diabetes mellitus (DM). Despite these interesting observations, to date, metformin is the only ethical drug approved for treatment of Type 2 DM derived from a medicinal plant. Why is this so, given the fact that higher plants are such a potential source of new drugs? The answer to this rhetorical question may lie in the reliance of most pharmaceutical companies on random, in vitro, mechanism-based, high throughput screening in the initial phases of plant drug research. In this article we describe an alternative pathway to discovery of drugs for the treatment of Type 2 DM: on based on an ethnomedical approach, involving ethnobotany and traditional medicine. In particular, we present evidence that cryptolepine, an indoloquinolone alkaloid isolated from Cryptolepis sanguinolenta, significantly lowers glucose when given orally to a mouse model of diabetes. The antihyperglycaemic effect of cryptolepine leads to a significant decline in plasma insulin concentration, associated with evidence of an enhancement in insulin-mediated glucose disposal. Finally, cryptolepine increases glucose uptake by 3T3-L1 cells. These data permit us to conclude that an ethnobotanical approach to drug discovery can identify a potentially useful drug for the treatment of Type 2 DM.

Ethnobotanical-directed discovery of the antihyperglycemic properties of cryptolepine: its isolation from Cryptolepis sanguinolenta, synthesis, and in vitro and in vivo activities.

Using an ethnobotanical approach in combination with in vivo-guided fractionation as a means for lead discovery, cryptolepine was isolated as an antihyperglycemic component of Cryptolepis sanguinolenta. Two syntheses of cryptolepine, including an unambiguous synthesis, are reported. The hydroiodide, hydrochloride, and hydrotrifluoromethanesulfonate (hydrotriflate) salts of cryptolepine were synthesized, and a comparison of their spectral properties and their in vitro activities in a 3T3-L1 glucose transport assay is made. Cryptolepine and its salt forms lower blood glucose in rodent models of type II diabetes. While a number of bioactivities have been reported for cryptolepine, this is the first report that cryptolepine possesses antihyperglycemic properties.

Two new modified trichothecenes from Fusarium sporotrichioides.

Two new modified trichothecenes, 2-deoxy-11-epi-3 alpha-hydroxysambucoin [1] and 2-deoxy-11-epi-12-acetyl-3 alpha-hydroxysambucoin [2], were isolated from Fusarium sporotrichioides culture. This is the first report of modified trichothecenes where the two six-membered rings are cis-fused. Structures were elucidated using gc-ms, nmr, X-ray crystallography, and other spectroscopic techniques. Compounds 1 and 2 were screened for relative cytotoxicity in cultured baby hamster kidney (BHK-21) cells and found to be non-toxic.

Two new trichothecenes from Fusarium sporotrichioides.

Two new trichothecenes, 8-n-pentanoylneosolaniol and 8-n-hexanoylneosolaniol, were isolated from corn grits cultured with Fusarium sporotrichioides. The structures of these compounds were elucidated using gc-ms, nmr, X-ray crystallography, and other spectroscopic techniques. Seven known trichothecenes were also isolated, and the relative cytotoxicity of these nine trichothecenes in cultured baby hamster kidney (BHK-21) cells was determined.