Alkaloids lipase inhibition

The plant alkaloid [194] castanospermine 4 was discovered to inhibit HIV syncytium formation and virus replication [195]. Activity could be improved in vitro by a factor of 40, employing the corresponding 6-0-butanoyl derivative 73 [196]. Unfortunately, it turned out that the latter did not show any significant benefits in vivo [197], pointing to the fact that the beneficial butanoyl group is cleaved by nonspecific hydrolysis by esterases or lipases before the compound reaches the desired place of antiviral action. Castanospermine was also found to be active against the measles virus... 

Kinetic inhibition experiments revealed that the molecular action of the base on the lipase is a noncompetitive inhibititm — i.e., the base attaches itself to the lipase at a site other than the active site - which inhibits the transformation of one enantiomer but not that of its mirror image. Moreover, the chirality of the base has only a marginal impact on the selectivity enhancement effect. The general applicability of this method - impeded by the high cost of morphinan alkaloids and their questionable use for large-scale synthesis — has been extended by the use of more simple amines such as N, A -dimethyl-4-methoxyphenethylamine (DMPA) [235]. 

Effects with the autonomous nervous system have also merited attention. Over the cardiovascular system anti arrhythmic 341), antieschemic (555), antihemorrhagic 348), antifibrillatory 346), PAF inhibition 435), vasorelaxant 449), and hypotensive activities (552) are some of the important biological effects reported for the protober-berine alkaloids in the period covered by this review. Also important to mention are the metabolic effects hypoglycemic 351,404), antihypercholesterolemic 350), bone resorption inhibition (5(56), osteoclast formation inhibition (566), lipase and lipogenesis inhibition 412,414), and prostaglandin synthesis inhibition 438), are a few of the reported activities related to metabolism. 

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