Meridianins: Marine-Derived Potent Kinase Inhibitors

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.

Racemosins A and B, two novel bisindole alkaloids from the green alga Caulerpa racemosa

“…Chemical shifts are expressed in δ (ppm) and coupling constants (J) in Hz. 1 H and 13 C NMR assignments were supported by 1 H-1 H COSY, HSQC, HMBC, and ROESY experiments. ESI-MS and HR-ESI-MS spectra were recorded on a Q-TOF Micro LC-MS-MS mass spectrometer.…”

“…Within the marine environment, numerous unique bisindole alkaloids such as meridianins [1], topsentins [2], nortopsentins [3], dragmacidins [4], variolins [5], and rhopaladins [6] have been reported from sponges [2][3][4][5], actinomycetes [7], tunicates [6] and green algae [8,9]. In addition, some of these marine bisindole compounds were found to be responsible for potent and diverse bioactive properties, e.g., antifungal [8,10], antibacterial [11], antiviral [12], cytotoxic [7], anti-inflammatory [13], and noteworthy antitumor [12,14] activities.…”

One-pot Synthesis of 2,3-Dihydroquinazolin-4(1H)-ones under Catalyst- and Solvent-free Conditions

“…Furthermore, the reaction conditions are sufficiently mild enough to tolerate a variety of functionalities such as Cl, Br, OH, OMe, -OCH 2 O-and NMe 2 . All the products (3) are known compounds and were identified by comparison of their physical and spectral data with those reported in the literature [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26]33 . From a mechanistic point of view, the process is possibly a general acidbase catalyzed condensation followed by cyclization 16,20 .…”

High‐Throughput Screening of Marine Resources

“…HTS assays have been developed using multiple technologies that include radioactivity-based assays, luminescent technology, TR-FRET, fluorescent polarization and scintillation proximity assays (SPAs). Screening campaigns have identi fied several marine compounds as protein kinase inhibitors (Leclerc et al , 2001;Bettayeb et al , 2007;Bharate et al , 2012;Debdab et al , 2011). One of these, Hymenialdisine (HMD) (Figure 23.5), was originally identified based on its antiproliferative effects on cultured lymphocytic leukemia cells, and characterized using an SPA.…”