Chemical and pharmacological information on cantharidin-based small molecules was analyzed. The review summarizes new facts about blister beetles' metabolites for the period 2006-2012. General synthetic approaches to cantharidin-based small molecules as well as their chemical transformations and biological activities related to cantharidin, norcantharidin, cantharidimide, and norcantharimide analogs, especially their inhibitory activity of phosphoprotein phosphatases in cancer treatment, were discussed in this mini review, which could help to design new small molecule modulators for other biological models.Key words: anticancer activity, blister beetles, cantharidin analogs, Diels-Alder cycloaddition reactions, drug design and development, protein phosphatases inhibitory activity With the development in the natural product chemistry, giving many interesting objects to study from the structural, synthetic, and pharmacological standpoints, the organic synthesis had evolved at the same rate with the generation of molecules/molecular assemblies with welldefined biological functions, and within this challenging task in the biology-oriented synthesis field, the design and development of more efficient chemical reactions and methodologies would revolutionize the next generation of chemical and biological research. Secondary metabolites of plants and animals are the main objects to study phytochemistry and organic chemistry, as shown by their centennial history that has successfully promoted the discovery and drug development. According to a recent analysis, in the last 25 years, nearly half of the drugs currently in clinical use belong to drugs of natural origin (1,2). Therefore, the success of drug discovery based on nature's secondary metabolites depends on how these natural substances are considered, mainly by medicinal and organic chemists, as source of inspiration rather than target molecules (3-6).For centuries, it has well known that many plants (shrubs, trees and grasses) possess a wide spectrum of medicinal properties and that bacterium and fungi are also capable of generating toxic constituents that inhibit the growth of other organisms in their proximity. These kingdoms have provided us more information, regarding the biological interactions of small molecules (SMs), to understand and encourage our investigations in the discovery and development of new SMs with marked physiological activities (7,8). In addition, these SMs are also useful for investigating biological systems as effective tools to elucidate the mechanism of important cellular processes that are based purely on (i) the performance of enzymatic reactions and (ii) protein-protein interactions, where the bioactive SMs are called bioprobes, and more importantly, (iii) the fact that they allow the rapid and conditional modulation of biological functions often in a reversible, dose-dependent manner (9,10).In contrast to plants and bacteria, the invertebrate animal kingdom, to which belong different insects (about a million species) including beetles,...
