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Several of the Amaryllidaceae alkaloids are known for their cytotoxic properties, of which the lycorine group representatives are prominent for potent and cell line specific antiproliferative activities. As a distinct niche within the lycorine group, the phenanthridones, exemplified by narciclasine and pancratistatin, have shown much promise as remarkably selective cytotoxic agents and are presently at various stages of development, with a clinical candidate likely to appear on the market within the next decade. The crinane group of the Amaryllidaceae has also spawned several molecules, such as crinamine and haemanthamine, with promising cytotoxic activities. In the present study, the β-crinane distichamine as well as the phenanthridone narciprimine, both rare constituents of the Amaryllidaceae, are revealed as novel antiproliferative agents. Apoptosis-inducing effects are demonstrated for distichamine in human acute lymphoblastic leukemia (CEM) cells. These findings provide further insights to the structural details of the apoptosis-inducing pharmacophores resident within both series of alkaloids.

The synthesis of differentially functionalized analogs of the Amaryllidaceae alkaloid lycorine, accessed via a concise chemoselective silylation strategy, is described uncovering two of the most potent inhibitors of acetylcholinesterase (AChE) identified to date in this series. Important elements of this novel pharmacophore were elucidated through structure-activity relationship (SAR) studies.

seco-Derivatives of the anticancer agent pancratistatin bearing the 2S,3S,4S,5S configuration were accessed via a novel, highly diastereoselective anti-aldol reaction. Structure–activity relationships reveal important insights into the seco-pancratistatin pharmacophore as a potent and selective inhibitor of human cytochrome P450 3A4 (CYP3A4), and highlight features of concern in advancing a potent, selective anticancer agent in the pancratistatin series.

A library of natural and semi-synthetic Amaryllidaceae alkaloids was screened for cytochrome P450 3A4 (CYP3A4) inhibitory activity. Of the crinane, lycorane and galanthamine representatives examined two semi-synthetic silylated lycorane analogues, accessed via a chemoselective silylation strategy from lycorine, and the natural compound narciclasine exhibited low micromolar activities. Important pharmacological features uncovered include the lack of CYP3A4 inhibitory activity seen for galanthamine and the selective activity that is seen with narciclasine over pancratistatin.

A general approach toward the rational design of potential inhibitors of serine proteinases is described. The approach is exemplified and validated through the use of appropriate heterocyclic systems in inhibiting human leukocytes elastase (HLE).

The design, synthesis, and inhibitory activity toward human neutropil elastase, of a series of potential mechanims-based inhibitors is described. The design, synthesis, and inhibitory activity toward human neutrophile elastase, of a series of potential mechanism-based inhibitor's (I-III) is described.