Microcos paniculata is a large shrub or small tree that grows in several countries in South and Southeast Asia. In the present study, three new piperidine alkaloids, microgrewiapines A-C (1-3), as well as three known compounds, inclusive of microcosamine A (4), 7′-(3′,4′-dihydroxyphenyl)-N-[4-methoxyphenyl)ethyl]propenamide (5), and liriodenine (6), were isolated from cytotoxic fractions of the separate chloroform-soluble extracts of the stem bark, branches, and leaves of M. paniculata. Compounds 1-6 and 1a showed a range of cytotoxicity values against the HT-29 human colon cancer cell line. When evaluated for their effects on human α3β4 or α4β2 nicotinic acetylcholine receptors (nAChRs), several of these compounds were shown to be active as nAChR antagonists. As a result of this study, microgrewiapine A (1) was found to be a selective cytotoxic agent for colon cancer cells over normal colon cells, and to exhibit nicotinic receptor antagonistic activity for both the hα3β4 and hα4β2 receptor subtypes.

Hematologic malignancies account for a substantial percentage of cancers worldwide, and the heterogeneity and biological characteristics of leukemias and lymphomas present unique therapeutic challenges. Although treatment options exist for most of these diseases, many types remain incurable and the emergence of drug resistance is pervasive. Thus, novel treatment approaches are essential to improve outcome. Nearly half of the agents used in cancer therapy today are either natural products or derivatives of natural products. The enormous chemical diversity in nature, coupled with millennia of biological selection, has generated a vast and underexplored reservoir of unique chemical structures with biologic activity. This review will describe the investigation and application of natural products derived from higher plants in the treatment of leukemia and lymphoma and the rationale behind these efforts. In addition to the approved vinca alkaloids and the epipodophyllotoxin derivatives, a number of other plant compounds have shown promise in clinical trials and in preclinical investigations. In particular, we will focus on the discovery and biological evaluation of the plant-derived agent silvestrol, which shows potential for additional development as a new therapeutic agent for B-cell malignancies including chronic lymphocytic leukemia.

Compounds from macro marine organisms are presumed to owe their biosynthetic origins to associated microbial symbionts, although few definitive examples exist. An upsurge in the recent literature from 2012 to 2013 has shown that four compounds previously reported from macro marine organisms are in fact biosynthesized by non-photosynthetic Gram-negative bacteria (NPGNB). Structural parallels between compounds isolated from macro marine organisms and NPGNB producers form the basis of this review. Although less attention has been given to investigating the chemistry of NPGNB sources, there exists a significant list of structural parallels between NPGNB and macro marine organism-derived compounds. Alternatively, of the thousands of compounds isolated from Gram-positive actinomycetes, few structural parallels with macro marine organisms are known. A summary of small molecules isolated from marine NPGNB sources is presented, including compounds isolated from marine myxobacteria. From this assemblage of structural parallels and diverse chemical structures, it is hypothesized that the potential for the discovery of inspirational molecules from NPGNB sources is vast and that the recent spike in the literature of macro marine compounds owing their biosynthetic origin to NPGNB producers represents a turning point in the field.

Gunnera is the only genus of angiosperms known to host cyanobacteria and the only group of land plants that hosts cyanobacteria intracellularly. Motile filaments of cyanobacteria, known as hormogonia, colonize Gunnera plants through cells in the plant's specialized stem glands. It is commonly held that Gunnera plants always possess functional glands for symbiosis. We found, however, that stem gland development did not occur when Gunnera manicata plants were grown on nitrogen (N)-replete medium but, rather, was initiated at predetermined positions when plants were deprived of combined N. While N status was the main determinant for gland development, an exogenous carbon source (sucrose) accelerated the process. Furthermore, a high level of sucrose stimulated the formation of callus-like tissue in place of the gland under N-replete conditions. Treatment of plants with the auxin transport inhibitor 1-naphthylphthalamic acid prevented gland development on N-limited medium, most likely by preventing resource reallocation from leaves to the stem. Optimized conditions were found for in vitro establishment of the Nostoc-Gunnera symbiosis by inoculating mature glands with hormogonia from Nostoc punctiforme, a cyanobacterium strain for which the full genome sequence is available. In contrast to uninoculated plants, G. manicata plants colonized by N. punctiforme were able to continue their growth on N-limited medium. Understanding the nature of the Gunnera plant's unusual adaptation to an N-limited environment may shed light on the evolution of plant-cyanobacterium symbioses and may suggest a route to establish productive associations between N-fixing cyanobacteria and crop plants.Nitrogen (N)-fixing cyanobacteria enter into symbiotic associations with a phylogenetically diverse group of eukaryotes ranging from fungi to vascular plants (Rai et al., 2000). Gunnera is the only flowering plant genus known to host cyanobacteria (Bonnett, 1990;Bergman et al., 1992;Bergman and Osborne, 2002). Plants in the genus Gunnera are mainly distributed in the southern hemisphere with about 40 species, which includes small, stoloniferous species (e.g. Gunnera magellanica) and plants 6 to 8 ft in height (e.g. Gunnera manicata). Even in the latter case, N 2 fixed by the symbiotic cyanobacteria, most likely in the form of NH 3 (Silvester et al., 1996), is able to fulfill the N needs of the plant (Osborne et al., 1991(Osborne et al., , 1992.In nature, Gunnera plants form symbioses with cyanobacteria belonging to the genus Nostoc (Bergman et al., 1992). Unlike other multicellular plant hosts, Gunnera harbors Nostoc intracellularly, surrounding the Nostoc filaments with a membrane most likely of plasma membrane origin (Silvester and McNamara, 1976;Johansson and Bergman, 1992). The specialized glands on the Gunnera stem serve as entry points for Nostoc filaments. Gunnera glands are conspicuously red due to the accumulation of anthocyanins such as pelargonidin and cyanidin (G. Lanigan, K.G. Black, and B. Osborne, unpublished data). Shortly after ge...