A new compound, clerodane diterpenoid, CD, was isolated from the bark of Polyalthia longifolia var. pendula. . In previously study, CD was proved to induce cell apoptosis. We analysis differentially expressed proteins of colorectal cancer cells under drug CD treatment by 2-D electrophoresis and find drug response proteins, e.g. Hsp10, Profilin-1, Peroxindoxin-1. The expression change of protein had been further confirmed by RT-PCR and western blotting. It is interesting to reveal the role of these proteins in the colorectal cancinogenesis and anti-tumor drug response. In most kind of cancers, Hsp10 is often overexpress as indicated in many reports. Under CD treatment, Hsp10 is down-regulation in our experiment. The major aim of this study is to investigate the effect of Hsp10 on colorectal cancer cell lines SW480, and also investigate the relation of Hsp10 to drug treatment. Here,we overexpress Hsp10 in SW480. MTT assay, and flow cytometric analysis are utilized to investigate the effect of Hsp10 and CD cytotoxicity when overrxpress Hsp10 in SW480.

We recently reported results from a high-throughput screening effort that identified 235 inhibitors of the Escherichia coli GroEL/ES chaperonin system [Bioorg. Med. Chem. Lett. 2014, 24, 786]. As the GroEL/ES chaperonin system is essential for growth under all conditions, we reasoned that targeting GroEL/ES with small molecule inhibitors could be a viable antibacterial strategy. Extending from our initial screen, we report here the antibacterial activities of 22 GroEL/ES inhibitors against a panel of Gram-positive and Gram-negative bacteria, including E. coli, Bacillus subtilis, Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter cloacae. GroEL/ES inhibitors were more effective at blocking the proliferation of Gram-positive bacteria, in particular S. aureus, where lead compounds exhibited antibiotic effects from the low-lM to mid-nM range. While several compounds inhibited the human HSP60/10 refolding cycle, some were able to selectively target the bacterial GroEL/ES system. Despite inhibiting HSP60/10, many compounds exhibited low to no cytotoxicity against human liver and kidney cell lines. Two lead candidates emerged from the panel, compounds 8 and 18, that exhibit >50-fold selectivity for inhibiting S. aureus growth compared to liver or kidney cell cytotoxicity. Compounds 8 and 18 inhibited drug-sensitive and methicillin-resistant S. aureus strains with potencies comparable to vancomycin, daptomycin, and streptomycin, and are promising candidates to explore for validating the GroEL/ES chaperonin system as a viable antibiotic target.