Merging chemistry and biology in emerging countries

Chemical biology is not a new discipline, as research at the interface of chemistry and biology has been growing for decades. However, the field still needs regional and global support in emerging countries. The meeting organized by Asian Chemical Biology Initiative in Bangkok, Thailand in January 2013, brought together regional communities of young and established researchers to nurture chemical biology research programs and highlight some of the newer developments. Here, we report on the meeting and some of the key research topics discussed

COMPOUND ANALYSIS VIA GRAPH KERNELS INCORPORATING CHIRALITY

High accuracy is paramount when predicting biochemical characteristics using Quantitative Structural-Property Relationships (QSPRs). Although existing graph-theoretic kernel methods combined with machine learning techniques are efficient for QSPR model construction, they cannot distinguish topologically identical chiral compounds which often exhibit different biological characteristics. In this paper, we propose a new method that extends the recently developed tree pattern graph kernel to accommodate stereoisomers. We show that Support Vector Regression (SVR) with a chiral graph kernel is useful for target property prediction by demonstrating its application to a set of human vitamin D receptor ligands currently under consideration for their potential anti-cancer effects

Inubosins A, B, and C Are Acridine Alkaloids Isolated from a Culture of <i>Streptomyces</i> sp. IFM 11440 with Ngn2 Promoter Activity

Three new acridine alkaloids, inubosins A (<b>1</b>), B (<b>2</b>), and C (<b>3</b>), were isolated from an extract of a culture of <i>Streptomyces</i> sp. IFM 11440 using bioassay-guided fractionation. Neurogenin2 (Ngn2) is an activator-type basic helix–loop–helix transcription factor that promotes neural stem cell differentiation. Using cell-based Ngn2 promoter activity-guided screening, <i>Streptomyces</i> sp. IFM 11440 was found to induce Ngn2 promoter activity. The structures of <b>1</b>–<b>3</b> were established using spectroscopic methods, including 1D- and 2D-NMR measurements. Inubosin B (<b>2</b>) showed potent Ngn2 promoter activity. Moreover, inubosin B (<b>2</b>) increased mRNA expression of genes related to neural stem cell differentiation

Physalin H from Solanum nigrum as an Hh signaling inhibitor blocks GLI1–DNA-complex formation

Hedgehog (Hh) signaling plays an important role in embryonic development, cell maintenance and cell proliferation. Moreover, Hh signaling contributes to the growth of cancer cells. Physalins are highly oxidized natural products with a complex structure. Physalins (1–7) were isolated from Solanum nigrum (Solanaceae) collected in Bangladesh by using our cell-based assay. The isolated physalins included the previously reported Hh inhibitors 5 and 6. Compounds 1 and 4 showed strong inhibition of GLI1 transcriptional activity, and exhibited cytotoxicity against cancer cell lines with an aberrant activation of Hh signaling. Compound 1 inhibited the production of the Hh-related proteins patched (PTCH) and BCL2. Analysis of the structures of different physalins showed that the left part of the physalins was important for Hh inhibitory activity. Interestingly, physalin H (1) disrupted GLI1 binding to its DNA binding domain, while the weak inhibitor physalin G (2) did not show inhibition of GLI1-DNA complex formation