Meridianins: Marine-Derived Potent Kinase Inhibitors

S.      B. Bharate; R.      R. Yadav; S.      Battula; R.      A. Vishwakarma

Abstract

Marine invertebrates are a rich source of novel, bioactive secondary metabolites and have attracted a great deal of attention from scientists in the fields of chemistry, pharmacology, ecology, and molecular biology. This profilic natural source has produced several antitumor secondary metabolites and amongst these, indole alkaloids are of wide occurrence. Meridianins A-G (1-7) are indole alkaloids isolated from tunicate Aplidium meridianum and are known to inhibit variety of protein kinases associated with cancer and neurodegenerative diseases. These compounds also exhibited promising antiproliferative activity in several cancer cell lines. Amongst natural meridianins, meridianin E (5) showed potent and selective inhibition of CDK-1 and CDK-5. Several synthetic meridianin analogs exhibited potent and selective inhibition of glycogen synthase-3 (GSK-3) and dual-specificity tyrosine-phosphorylation regulated kinase 1A (Dyrk-1A) which are known to be implicated in progression of Alzheimer’s disease. The present review provides the critical account of isolation, medicinal chemistry and pharmacology of meridianins. Our analysis of the structure-activity relationships of this family of compounds highlights the existence of various potential leads for the development of novel anticancer and anti-Alzheimer’s agents.

Keywords: Anticancer, antimalarial, kinase inhibitors, marine natural product, meridianins, 2-aminopyrimidine, hydroxyl, 2, 4-dichloro pyrimidine, 2-amino-4-chloropyrimidine, 3-iodoindole