[Study on the chemical constituents of Phryma leptostachya].

OBJECTIVE: To study the chemical constituents of Phryma leptostachya. METHODS: The chemical constituents were isolated and purified by silica gel column, recrystallization and Pre-RP-HPLC and their structwes were elucidated by spectroscopic methods. RESULTS: Five compounds were obtained and identified as ursolic acid (1), quercetin (2), isovanillic acid (3), p-hydroxybenzoic acid (4), adenine arabinoside (5). CONCLUSION: Compounds 2 - 5 are isolated from this genus for the first time.

Antiviral lead compounds from marine sponges.

Marine sponges are currently one of the richest sources of pharmacologically active compounds found in the marine environment. These bioactive molecules are often secondary metabolites, whose main function is to enable and/or modulate cellular communication and defense. They are usually produced by functional enzyme clusters in sponges and/or their associated symbiotic microorganisms. Natural product lead compounds from sponges have often been found to be promising pharmaceutical agents. Several of them have successfully been approved as antiviral agents for clinical use or have been advanced to the late stages of clinical trials. Most of these drugs are used for the treatment of human immunodeficiency virus (HIV) and herpes simplex virus (HSV). The most important antiviral lead of marine origin reported thus far is nucleoside Ara-A (vidarabine) isolated from sponge Tethya crypta. It inhibits viral DNA polymerase and DNA synthesis of herpes, vaccinica and varicella zoster viruses. However due to the discovery of new types of viruses and emergence of drug resistant strains, it is necessary to develop new antiviral lead compounds continuously. Several sponge derived antiviral lead compounds which are hoped to be developed as future drugs are discussed in this review. Supply problems are usually the major bottleneck to the development of these compounds as drugs during clinical trials. However advances in the field of metagenomics and high throughput microbial cultivation has raised the possibility that these techniques could lead to the cost-effective large scale production of such compounds. Perspectives on biotechnological methods with respect to marine drug development are also discussed.

Herbicidal nucleosides from microbial sources.

The structures of five naturally-occurring herbicidal nucleosides have been determined by spectral analysis. Three (5'-deoxyguanosine, coaristeromycin and 5'-deoxytoyocamycin) are novel natural products while the remaining two (coformycin and adenine 9-beta-D-arabinofuranoside) are known natural products which have not previously been reported to be herbicidal.

Alkali lability of deoxyribonucleic acid that contains adenine arabinoside.

We have demonstrated previously that 9-beta-D-arabinofuranosyl adenosine (ara-A), like 1-beta-D-arabinofuranosyl cytosine (ara-C), incorporates exclusively into DNA, not RNA [Kufe et al., Cancer Res. 43, 2000 (1983)]. We have also demonstrated that (ara-C)DNA is degraded by alkali [Major et al., Biochem. Pharmac. 31, 861 (1982)], suggesting a structural instability of this abnormal nucleic acid. These findings have been extended by investigating the effects of various alkaline conditions on ara-A and (ara-A)DNA. The results indicate that the nucleoside was degraded under stringent conditions (0.4 M NaOH, 0.5 hr, 100 degrees) and that a similar effect occurred following exposure of (ara-A)DNA. The results also indicate that milder alkaline conditions (0.4 M NaOH, 6 hr, 37 degrees) resulted in strand scission of (ara-A)DNA at the 3'-carbon of the incorporated arabinosyl sugar without degradation of the ara-A moiety itself. These findings may be useful when attempting to purify (ara-A)DNA and confirm the structural instability of arabinosyl-containing DNA.