Inhibitory activities of (-)-epigallocatechin-3-O-gallate against topoisomerases I and II.

The substitution of gallic acid at the 3 position of (-)-epigallocatechin-3-O-gallate (EGCG) increased the inhibition against topoisomerase I from calf thymus gland and topoisomerase II from human placenta, and the substitution of a hydroxyl group at the 3' position increased the inhibition against the topoisomerase I. These results suggested that the 3 and 3' positions of the EGCG molecule play important roles in the process of inhibition of topoisomerases I and II. EGCG showed strong inhibition against topoisomerases I from wheat germ, calf thymus gland and Vero cells, and showed weak or no inhibition against topoisomerases I from carcinoma cells such as A549, HeLa and COLO 201 cells. EGCG differentially inhibited the topoisomerases I from different sources.

Anti-herpes virus activity of Solanum steroidal glycosides.

Since some Solanum-genus plants have traditionally been used for anti-cancer and anti-herpes agents from olden times, we examined anti-herpes simplex virus type 1 (HSV-1) activity of typical steroidal glycosides with the frameworks of spirostane (including nuatigenin glycoside), furostane, solasodane, tomatidane and ergostane (including dimer) obtained from Solanum plants. Among these steroidal glycosides, the spirostanol glycosides were most effective. An inclination was observed for the potency of activity to decrease in the order of spirostane, tomatidane, ergostane, solasodane, nuatigenin type, dimer of ergostane and furostane. It was also suggested that the activity depends on the kind of oligosacchride moiety.

Inhibition of DNA topoisomerases by microbial inhibitors.

New inhibitors of DNA topoisomerase named 2280-DTI and 2890-DTI have been discovered in the culture filtrates of Micromonospora sp. strain No. 2280 and Streptomyces sp. strain No. 2890, respectively. Both inhibitors were purified from each culture filtrate by column chromatography on Diaion, Dowex and gel filtration. Both inhibitors were thermostable acidic substances with high molecular weight and inhibited topoisomerase I in a non-competitive manner. They differed from well-known inhibitors of topoisomerases such as camptothecin and doxorubicin, which inhibit the DNA rejoining reaction of the enzyme by intercalation into DNA strands or stabilizing the cleavable complex (enzyme-DNA reaction intermediate). 2280-DTI and 2890-DTI did not intercalate into DNA strands and also had no ability to stabilize the cleavable complex. It is suggested that 2280-DTI and 2890-DTI inhibit the DNA breaking and rejoining reactions of topoisomerase by direct action on the enzyme molecule.

Evaluation of the efficacy of a 3.2% glutaraldehyde product for disinfection of fibreoptic endoscopes with an automatic machine.

The efficacy of 'Cidex Plus' 3.2% alkaline glutaraldehyde was evaluated for the disinfection of fibreoptic endoscopes. The glutaraldehyde concentration in 'Cidex Plus', stored in an automatic machine (Olympus EW-20), remained higher than 2% (2.21%) even after a total of 102 disinfection cycles during 28 consecutive days. The results of the in-vitro study on antimicrobial activity showed that this alkaline glutaraldehyde product had a greater activity against 20 test organisms, including vegetative bacteria, bacterial spores, mycobacteria, and fungi, than 2% glutaraldehyde alone. The presence of 10 or 30% human serum did not appear to affect the activity of glutaraldehyde adversely. Instrument samples made from a variety of materials such as stainless steel, glass, teflon, etc. were not damaged after 168 h of immersion in alkaline glutaraldehyde, although it contained approximately 1.7 times more glutaraldehyde than 2% glutaraldehyde alone. Based on these results, 3.2% alkaline glutaraldehyde is considered to be a more effective disinfectant for fibreoptic endoscopes, with the use of an automatic machine, than 2% glutaraldehyde.