Preclinical and clinical studies on bryostatins, a class of marine-derived protein kinase C modulators: A mini-review.

Preclinical and clinical studies on bryostatins, a class of marine-derived protein kinase C modulators: A mini-review. Curr Top Med Chem. 2020 Mar 25;: Authors: Raghuvanshi R, Bharate S Abstract Bryostatins are complex macrolactones isolated from marine organism Bryozoan Bugula neritina. They are potent modulators of protein kinase C isozymes (PKCα: ki = 1.3-188 nM), and are one of the most extensively investigated marine natural products in clinical trials. Although ~21 natural bryostatins have been isolated, however only bryostatin-1 (1) has received much interest among medicinal chemists and clinicians. The structure-activity relationship of bryostatins has been well established, with the identification of key pharmacopjoric features important for PKC modulation. The low natural abundance and long synthetic route has promoted medicinal chemists to come-up with simplified analogs. Bryostatin skeleton primarily comprises three pyran rings connected to each other to form a macrocyclic lactone. The simplest analog 27 contains only one pyran, which is also able to modulate the PKCα activity, however the cyclic framework appears to be essential for desired potency. Another simplified analog 17 ("picolog") exhibited potent in vitro and in-vivo efficacy against lymphoma. Bryostatin-1 (1) has shown acceptable IV pharmacokinetic profile in mice and displayed promising in-vivo efficacy in mice models of various cancers and Alzheimer's dise...
Source: Current Topics in Medicinal Chemistry - Category: Chemistry Authors: Tags: Curr Top Med Chem Source Type: research