Cadinane sesquiterpenoids, strobilols L and M, from Strobilurus ohshimae.

Strobilols L and M, which are cadinane sesquiterpene derivatives, were isolated from the liquid culture of the edible mushroom Strobilurus ohshimae. Their structures have been established on the basis of spectral analyses. Strobilols A-M were examined for their growth inhibition activity against human cancer cell lines YMB and COLO 201.

Two cyathane-type diterpenoids from the liquid culture of Strobilurus tenacellus.

The structures of two new cyathane-type diterpenoids isolated from a liquid culture of Strobilurus tenacellus have been elucidated. The chemical structures of the new compounds 1 and 2 were identified as (12S)-11alpha,14alpha-epoxy-13alpha,14beta,15-trihydroxycyath-3-ene and (12R)-11alpha,14alpha-epoxy-13alpha,14beta,15-trihydroxycyath-3-ene, respectively, by spectral methods, including HR-EI-MS, and 1D- and 2D-NMR techniques. Compounds 1 and 2 show antimicrobial activity against Pseudomonas aeruginosa. In addition, both compounds were also tested for activity against human cancer cells, and 2 showed growth inhibitory activity against YMB and COLO 201 cells.

Fusaristatins A and B, two new cyclic lipopeptides from an endophytic Fusarium sp.

Two new cyclic lipopeptides, fusaristatins A (1) and B (2) were isolated from rice cultures of a Fusarium sp. YG-45 in the course of a screening of endophytic fungi. Their structures of 1 and 2 were determined by spectroscopic methods. 2 showed a moderate inhibitory effect on topoisomerases I (IC50: 73 microM) and II (IC50: 98 microM) without cleavable complexes. Furthermore, 1 and 2 showed the growth-inhibitory activity toward lung cancer cells LU 65 with IC50 values of 23 and 7 microM, respectively.

Effects of chelating agents on distribution and excretion of terbium in mice.

When terbium chloride (TbCl(3)) was intravenously injected into mice, terbium (Tb) was mainly distributed into the spleen, lung, and liver. Thus, the effects of five chelating agents on the distribution of Tb to the spleen, lung, and liver of mice were examined. The treatments with diethyldithiocarbamate (DDTC), N-p-methoxybenzyl-D-glucamine dithiocarbamate (MeOBGD) and 2,3-dimercaptopropanol (BAL) reduced the content of Tb in the spleen. The treatments with D-penicillamine (D-PEN), ethylenediaminetetraacetic acid (EDTA), and MeOBGD reduced the content of Tb in the lung. However, BAL treatment enhanced the content of Tb in the lung, indicating the redistribution of Tb to the tissue. Although the biliary excretion of Tb was significantly increased in mice treated with EDTA and MeOBGD, these increases were negligibly small, and the metal was not detected in the urine. These results indicate that well-known chelating agents such as D-PEN, EDTA, DDTC, MeOBGD, and BAL have little ability to excrete Tb into the bile and urine. Further studies are necessary to develop a new type of chelating agent to remove Tb effectively from the body.

Structure-effect relationship in the mobilization of cadmium in mice by several dithiocarbamates.

The structural characteristics of several dithiocarbamates (DTCs) [N-p-methylbenzyl-D-glucamine dithiocarbamate (MBGD), N-benzyl-D-glucamine dithiocarbamate (BGD), N-p-hydroxymethylbenzyl-D-glucamine dithiocarbamate (HBGD) and N-p-carboxybenzyl-D-glucamine dithiocarbamate (CBGD)] that induce in vivo mobilization of cadmium (Cd) were examined in mice. The renal and hepatic contents of Cd were lower in the treatments with Cd-DTC combinations than in that with Cd alone. Probenecid pretreatment decreased the renal content of Cd in Cd-MBGD and Cd-BGD treated mice, but it increased the renal content of Cd and decreased the urinary excretion of the metal in Cd-HBGD and Cd-CBGD treated mice. Furthermore, although ureter-ligation did not affect the renal content of Cd in Cd-MBGD and Cd-BGD treated mice, it increased the renal content of Cd in Cd-HBGD and Cd-CBGD treated mice. These findings suggest that Cd-MBGD and Cd-BGD complexes are taken up into the tubular cells by an organic anion transport system through the basolateral membrane, whereas Cd-HBGD and Cd-CBGD complexes are secreted to the tubular lumen by an organic anion transport system through the brush border membrane. The results of probenecid pretreatment also led us to assume that the hepatic transport of these four Cd-DTC complexes is regulated, at least in part, by a probenecid-sensitive organic anion transport system.

Involvement of active transport systems in the mobilization of cadmium by dithiocarbamates in vivo.

Previously, we reported that the action of cadmium (Cd) complexing dithiocarbamates, such as N-benzyl-D-glucamine dithiocarbamate (BGD) and N-p-hydroxymethylbenzyl-D-glucamine dithiocarbamate (HBGD), in removing Cd from the kidney involves a probenecid-sensitive organic anion transport system. However, other mechanisms responsible for Cd mobilizing effects of BGD and HBGD are still unclear. Therefore, in the present study we examined the effects of phloretin (an inhibitor of plasma membrane glucose carrier), phloridzin (an inhibitor of Na(+)-dependent active hexose transport) and alpha-aminoisobutyric acid (AIB, an inhibitor of amino acid transport) on the excretion and distribution of the chelating agents and Cd in mice. Phloretin pretreatment markedly decreased the biliary and urinary excretions of BGD and HBGD. Phloridzin pretreatment also decreased the biliary and urinary excretions of HBGD, but had no effect on the BGD. AIB pretreatment had no effect on the excretions of either BGD or HBGD. Phloretin pretreatment increased the hepatic and renal contents of BGD and HBGD. Contrary to this, phloridzin pretreatment decreased the hepatic content of BGD and hepatic and renal contents of HBGD, while AIB pretreatment decreased the renal contents of BGD and HBGD. The mobilizing effects of BGD and HBGD on the hepatic and renal Cd was also investigated using Cd-exposed mice. Phloretin or phloridzin pretreatment decreased the mobilizing effect of BGD and HBGD on the hepatic Cd, but had no effect on the renal Cd. These results suggest that BGD and HBGD are taken up into the liver and kidney by phloridzin- and phloretin-sensitive transport system, respectively; that Cd-BGD and Cd-HBGD complexes formed in the hepatic cells are secreted to the bile by phloridzin- and phloretin-sensitive transport systems; and that free BGD and HBGD secreted from these organ to the bile and urine might have occurred, at least in part, by different mechanisms.