STRUCTURE-ACTIVITY STUDIES OF PHOTOACTIVATED ANTIVIRAL AND CYTOTOXIC TRICYCLIC THIOPHENES

The photoactivated antiviral and cytotoxic activities of the naturally occurring thiophene, alpha-terthienyl (1), and 15 synthetic analogues were evaluated against murine cytomegalovirus and Sindbis virus, and murine mastocytoma cells. After irradiation with near UV light, alpha-terthienyl and most of its analogues had significant toxicity, with minimum inhibitory concentrations in the range of 0.02-40 microM. In the absence of near UV irradiation, only one analogue had antiviral activity and five were cytotoxic. The most active analogues were those containing carboxylic acid, hydroxyl, or cyano substituents. Quantitative structure-activity relationship analysis of thiophene phototoxicity suggested that the rate of singlet oxygen production is the primary determinant of antiviral and cytotoxic activities. For phototoxicity against murine cytomegalovirus, a significant role for hydrophobicity was also demonstrated. Tricyclic thiophenes show significant potential for photochemotherapy of viral infections and cancer, and further evaluation in animal models is recommended.     

Chromone and flavonoid alkaloids: occurrence and bioactivity

The chromone and flavonoid alkaloids represent an unusual group of structurally diverse secondary metabolites, derived from the convergence of multiple biosynthetic pathways that are widely distributed through the plant and animal kingdoms. Many of them have been discovered through bioassay-guided chemical investigations of traditional medicines, suggesting potential therapeutic significance. Their unique structures and varied pharmacological activities may provide important new leads for the discovery of drugs with novel mechanisms of action. Potential therapeutic indications are as diverse as cancer and viral infections, inflammation and immunomodulation, neurological and psychiatric conditions, and diabetes.     

THE ANTI-HIV ACTIVITIES OF PHOTOACTIVE TERTHIOPHENES

Abstract— Various synthetic analogues of the naturally occurring terthiophene, α-terthienyl (αT), were evaluated for anti-human immunodeficiency virus (HIV) activity. The compounds were incubated individually with a known amount of the virus, with or without UVA radiation (long-wavelength ultraviolet) and residual virus was monitored for its ability to produce cytopathic effects in cell culture and the production of virus-specific protein (p24). The basic terthiophene structure was essential for good anti-HIV activity, although various side chains, such as alcohols, bromo, methyl, thiomethyl and trimethylsilyl groups, permitted retention of maximum activity. Under optimum conditions, as little as 12 ng/mL of these compounds ( i.e approximately 3 × 10⁻⁸ M ) could inactivate 10³ infectious virions. None of the compounds however were more active than αT itself. In all cases, UVA radiation was essential. Several side chains decreased the antiviral efficacy, and some side chains abrogated the activity.     

Monocyclic phenolic acids; hydroxy- and polyhydroxybenzoic acids: occurrence and recent bioactivity studies

Among the wide diversity of naturally occurring phenolic acids, at least 30 hydroxy- and polyhydroxybenzoic acids have been reported in the last 10 years to have biological activities. The chemical structures, natural occurrence throughout the plant, algal, bacterial, fungal and animal kingdoms, and recently described bioactivities of these phenolic and polyphenolic acids are reviewed to illustrate their wide distribution, biological and ecological importance, and potential as new leads for the development of pharmaceutical and agricultural products to improve human health and nutrition.     

Thioglycosynthases: double mutant glycosidases that serve as scaffolds for thioglycoside synthesis

A double mutant, retaining glycosidase that lacks both the catalytic nucleophile and the catalytic acid/base residues efficiently catalyzes thioglycoside formation from a glycosyl fluoride donor and thiosugar acceptors.     

Experiments on jet/vortex interaction

An experimental study was performed to evaluate the effect of a cold jet on a single trailing vortex. Flow visualization and particle image velocimetry (PIV) measurements were conducted in wind and water tunnels. The main parameters were the ratio of jet-to-vortex strength, the jet-to-vortex distance, the jet inclination angle and the Reynolds number. It was shown that the jet turbulence is wrapped around the vortex and ingested into it. This takes place faster with decreasing jet-to-vortex distance and increasing jet strength. Both time-averaged and instantaneous flow fields showed that the trailing vortex became diffused with its rotational velocity and vorticity levels reduced when the jet is located close to the vortex. The mechanism with which the jet interacts with the vortex is a combination of vortices shed by the jet and the turbulence. No noticeable differences were found within the Reynolds number range tested. The effect of jet on the vortex is delayed when the jet is blowing at an angle to the free stream and away from the vortex such as during take-off.