Bicyclic polyprenylated acylphloroglucinols and their derivatives: structural modification, structure-activity relationship, biological activity and mechanism of action.

Bicyclic polyprenylated acylphloroglucinols (BPAPs), the principal bioactive benzophenone products isolated from plants of genera Garcinia and Hypericum, have attracted noticeable attention from the synthetic and biological communities due to their fascinating chemical structures and promising biological activities. However, the potential drug interaction, undesired physiochemical properties and toxicity have limited their potential use and development. In the last decade, pharmaceutical research on the structural modifications, structure-activity relationships (SARs) and mechanisms of action of BPAPs has been greatly developed to overcome the challenges. A comprehensive review of these scientific literature is extremely needed to give an overview of the rapidly emerging area and facilitate research related to BPAPs. This review, containing over 226 references, covers the progress made in the chemical synthesis-based structure modifications, SARs and the mechanism of action of BPAPs in vivo and vitro. The most relevant articles will focus on the discovery of lead compounds via synthetic modifications and the important BPAPs for which the direct targets have been deciphered. From this review, several key points of the SARs and mode of actions of this novel class of compounds have been summarized. The perspective and future direction of the research on BPAPs are concluded. This review would be helpful to get a better grasp of medicinal research of BPAPs and become a compelling guide for chemists dedicated to the synthesis of these compounds.