Novel Antitumor Agents: Marine Sponge Alkaloids, their Synthetic Analogs and Derivatives

Abstract

Present review describes research on novel natural antitumor agents isolated from marine sponges. More than 90 novel cytotoxic antitumor compounds and their synthetic analogs have shown confirmed activity in vitro tumor cell lines bioassay and are of current interest to NCI for further in vivo evaluation. A great problem, to use directly the reservoir of marine organisms for therapy is the very low availability and the isolation of only very small amounts of the biologically active substances from the natural materials. Thus, the synthetic chemistry is required to develop high yield synthetic methods, which are able to produce sufficient marine alkaloids for a broad biological screening. This review will present some of the aspects of the medicinal chemistry developed recently to introduce such modifications. The structures, origins, synthesis and biological activity of a selection of N-heterocyclic marine sponge alkaloids are reviewed. The emphasis is on compounds poised as potential anticancer drugs: pyrroles, pyrazines, imidazole, and other structural families. With computer program PASS some additional biological activities are also predicted, which point toward new possible applications of these compounds. This review emphasizes the role of marine sponge alkaloids as an important source of leads for drug discovery.

Guanidinium-based sulfonic acid as a new Brønsted acid organocatalyst in organic synthesis in water

“…In this regard, DAMN, acetone, and cyclohexyl isocyanide were stirred in the presence of guanidinium-based sulfonic acid as an acidic organocatalyst in water to lead to the synthesis of 5-(cyclohexylamino)-1,6-dihydro-6,6-dimethylpyrazine-2,3-dicarbonitrile 6a in 90 % yield. As indicated in Table 2 (entries [13][14][15][16][17], to evaluate the use of this approach, a variety of aliphatic and aromatic ketones and various isocyanides with DAMN were condensed under similar circumstances. The reactions proceeded very cleanly, and no undesirable side reactions were observed.…”

“…It is important to note that the synthetic potentialities of MCRs with SO 3 H-functionalized Brønsted acid as environmentally benign and a recyclable catalyst have been combined to prepare quinoxalines [16] and pyrazines [17][18][19][20][21][22], which are seen in some important marketed drugs (I-III) [23][24][25], and urazole derivatives which also exhibit biological activities (IV-VII) [26][27][28][29] (Fig. 1).…”

Prediction of Activity Spectra of Substances Assisted Prediction of Biological Activity Spectra of Potential Anti-Alzheimer’s Phytoconstituents

“…The applicability of PASS to phytoconstituents has been exhibited in earlier investigations [12][13][14]. The current version of PASS is capable of predicting over 3750 biological effects, biochemical modes of action, specific toxicities, and metabolic terms based on 2D structures or canonical simplified molecular-input line-entry system (SMILES) with a mean accuracy of almost 95%.…”

Antiamoebic Activity of Marine Sponge Spongia officinalis var. ceylonensis Dendy

“…Marine sponges are incredible source of novel pharmacologically active compounds (Thomas et al, 2010) which have earlier shown potent efficacy against various diseases. They are known to possess diverse pharmacological activity in several diseases such as cancer, neurodegeneration, type-2-diabetes, fungal and microbial infections (Bhosale et al, 1999;Dembitsky et al, 2005;Rao et al, 2006;Coello et al, 2009;Guzmán et al, 2011;Takei et al, 2010). These biological activities have been attributed to the presence of novel sterols, metabolites including steroids, terpenoids, alkaloids, cyclic peptides and unsaturated fatty acids (Litchfield et al, 1976;Findlay and Patil, 1985;Elenkov et al, 1999).…”