Colchicine, the main alkaloid of Colchicum autumnale, is one of the most famous natural molecules. Although colchicine belongs to the oldest drugs (in use since 1500 BC), its pharmacological potential as a lead structure is not yet fully exploited. This review is devoted to the synthesis and structure− activity relationships (SAR) of colchicine alkaloids and their analogues with modified A, B, and C rings, as well as hybrid compounds derived from colchicinoids including prodrugs, conjugates, and delivery systems. The systematization of a vast amount of information presented to date will create a paradigm for future studies of colchicinoids for neoplastic and various other diseases.

Enzyme-responsive liposomes release their cargo in response to pathologically increased levels of enzymes at the target site. We report herein an assembly of phospholipase A2-responsive liposomes based on colchicinoid lipid prodrugs incorporated into lipid bilayer of the nanosized vesicles. The liposomes were constructed to addresses two important issues: (i) the lipid prodrugs were designed to fit the structure of the enzyme binding site; and (ii) the concept of lateral pressure profile was used to design lipid prodrugs that introduce almost no distortions into the lipid bilayer packing, thus ensuring that corresponding liposomes are stable. The colchicinoid agents exhibit antiproliferative activity in subnanomolar range of concentrations.

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