Org Lett. 2009 Aug 24; Chen HD, He XF, Ai J, Geng MY, Yue JMTrigochilides A (1) and B (2), two highly modified daphnane-type diterpenoids with 12-carbon-containing polyketide appendages at C-16 forming a macro-lactone with C-3, were isolated from the twigs and leaves of Trigonostemon chinensis. Their structures were elucidated by spectroscopic analysis. Trigochilides A (1) showed modest cytotoxicity against two tumor cell lines.

Acta Pharmacol Sin. 2009 Aug 24; Zhang X, Zhou Y, Shen Y, Du LL, Chen JH, Leng Y, Shen JHAbstractAim:To design and synthese a novel class of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) inhibitors, featuring the (phenylsulfonamido-methyl)pyridine and (phenylsulfonamido-methyl)thiazole framework.Methods:Our initial lead 4-(phenylsulfonamido-methyl)benzamides were modified. Inhibition of human and mouse 11beta-HSD1 enzymatic activities by the new compounds was determined by a scintillation proximity assay (SPA) using microsomes containing 11beta-HSD1.Results:Sixteen new compounds (6a-6h, 7a-7h) were designed, synthesized and bioassayed. In dose-response studies, several compounds showed strong inhibitory activities with IC(50) values at nanomolar or low nanomolar concentrations. Structure-activity relationships are also discussed with respect to molecular docking results.Conclusion:This study provides two promising new templates for 11beta-HSD1 inhibitors.Acta Pharmacologica Sinica advance online publication, 24 August 2009; doi: 10.1038/aps.2009.118.

J Phys Chem B. 2009 Aug 26; Lu Y, Wang Y, Xu Z, Yan X, Luo X, Jiang H, Zhu WThe hydrogen bond acceptor capability of halogens has long been underappreciated in the field of biology. In this work, we have surveyed structures of protein complexes with halogenated ligands to characterize geometrical preferences of C-X...H contacts and contributions of such interactions to protein-ligand binding affinity. Notably, F...H interactions in biomolecules exhibit a remarkably different behavior as compared to three other kinds of X...H (X = Cl, Br, I) interactions, which has been rationalized by means of ab initio calculations using simple model systems. The C-X...H contacts in biological systems are characterized as weak hydrogen bonding interactions. Furthermore, the electrophile "head on" and nucleophile "side on" interactions of halogens have been extensively investigated through the examination of interactions in protein structures and a two-layer ONIOM-based QM/MM method. In biomolecular systems, C-X...H contacts are recognized as secondary interaction contributions to C-X...O halogen bonds that play important roles in conferring specificity and affinity for halogenated ligands. The results presented here are within the context of their potential applications in drug design, including relevance to the development of accurate force fields for halogens.