The Halichondria sponge-derived fungus, Gymnacella dankaliensis, was cultured in two different media conditions. A modified malt extract medium containing soluble starch instead of glucose resulted in two extremely unusual steroids, dankasterones A (2) and B (3), while four additional unusual steroids, gymnasterones A (4), B (5), C (6), and D (7), were isolated from the original malt extract medium. Their stereostructures have been established on the basis of spectroscopic analyses along with X-ray crystal structure analyses, modified Mosher's method, CD exciton method, and a chemical transformation. All the steroids except for 4 exhibited significant growth inhibition against the murine P388 cancer cell line. Dankasterone A (2) also exhibited potent growth inhibition against human cancer cell lines.

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Bioassay-guided (P388 lymphocytic leukemia cell line) separation of extracts prepared from the leaves, stems, and pods of Bauhinia purpurea, and, in parallel, its roots, led to the isolation of four new dibenz[b,f]oxepins (2a, 3-5) named bauhiniastatins 1-4, as well as the known and related pacharin (1) as cancer cell growth inhibitors. The occurrence of oxepin derivatives in nature is quite rare. Bauhiniastatins 1-4 were found to exhibit significant growth inhibition against a minipanel of human cancer cell lines, and bauhiniastatin 1 (2a) was also found to inhibit the P388 cancer cell line. Structures for these new cancer cell growth inhibitors were established by spectroscopic techniques that included HRMS and 2D NMR.

In order to make clear the structural role of the C-terminal amide group of endomorphin-2 (EM2, H-Tyr-Pro-Phe-Phe-NH2), an endogenous mu-receptor ligand, in the biological function, the solution conformations of endomorphin-2 and its C-terminal free acid (EM2OH, H-Tyr-Pro-Phe-Phe-OH), studied using two-dimensional 1H NMR measurements and molecular modeling calculations, were compared. Both peptides were in equilibrium between the cis and trans isomers around the Tyr-Pro omega bond in a population ratio of approximately/= 1:2. The lack of significant temperature and concentration dependence of NH protons suggested that the NMR spectra reflected the conformational features of the respective molecules themselves. Fifty possible 3D structures for the each isomer were generated by the dynamical simulated annealing method under the proton-proton distance constraints derived from the ROE cross-peaks. These energy-minimized conformers, which were all in the phi torsion angles estimated from J(NHCalphaH) coupling constants within +/- 30 degrees, were then classified in groups one or two according to the folding backbone structures. All trans and cis EM2 conformers adopt an open conformation in which their extended backbone structures are twisted at the Pro2-Phe3 moiety. In contrast, the trans and cis conformers of EM2OH show conformational variation between the 'bow'-shaped extended and folded backbone structures, although the cis conformers of its zwitterionic form are refined into the folded structure of the close disposition of C- and N-terminal groups. These results indicate clearly that the substitution of carboxyl group for C-terminal amide group makes the peptide flexible. The conformational requirement for mu-receptor activation has been discussed based on the active form proposed for endomorphin-1 and by comparing conformational features of EM2 and EM2OH.