Peloruside E (22-Norpeloruside A), a Pelorusane Macrolide from the New Zealand Marine Sponge Mycale hentscheli, Retains Microtubule-Stabilizing Properties.

A new peloruside congener, peloruside E (5), has been isolated in sub-milligram quantities from a specimen of the New Zealand marine sponge Mycale hentscheli. The structure of 5 differs from the parent compound peloruside A (1) by replacement of the C-10 gem-dimethyl moiety with a monomethyl substituent and represents the first structural deviation in the pelorusane scaffold. Peloruside E (5) is potently antiproliferative (HL-60, IC50 90 nM, cf. 1, 19 nM) and polymerizes purified tubulin, albeit at a rate lower than that of 1.

A review of monoamine oxidase (MAO) inhibitors in tobacco or tobacco smoke.

Tobacco smoking is reputed to be the most difficult addiction of all to give up, and nicotine has been noted as the major addictive agent in tobacco smoke. However, research shows that nicotine addiction is due to more than nicotine alone. One hypothesis is that monoamine oxidase (MAO) inhibition from non-nicotinic components in, or derived from, tobacco smoke contributes to nicotine addiction. Harman and norharman, have been recognised as major and potent MAO inhibitors in tobacco smoke, but these two inhibitors together comprise perhaps less than 10% of the total MAO A inhibitory activity in cigarette smoke suggesting other unidentified components may make significant contributions to total inhibitory activity. Therefore, we reviewed an index of the chemical components of tobacco and tobacco smoke and identified those known to be MAO inhibitors. Amongst these inhibitors, phenols and phenolic acids with MAO inhibitory activity are commonly reversible and selective MAO A inhibitors, whereas trans,trans-farnesol, 2-methyl-1,4-naphthoquinone (menadione), 1,4-naphthoquinone, scopoletin, and diosmetin with MAO inhibitory activity are reversible and selective MAO B inhibitors. The compound, 1,4-benzoquinone is an irreversible MAO A inhibitor and to the best of our knowledge, this is the first irreversible MAO A inhibitor to be reported in tobacco smoke. MAO inhibitors have been used clinically to treat depression, anxiety, and Parkinson's disease. The MAO inhibitors identified from tobacco and tobacco smoke and summarized in this review, are potential pharmacological candidates to be investigated further. This review will enhance our knowledge of the way tobacco smoke affects MAO activity in smokers and will also be important in helping to understand nicotine addiction.

Biologically Active Compounds Present in Tobacco Smoke: Potential Interactions Between Smoking and Mental Health.

Tobacco dependence remains one of the major preventable causes of premature morbidity and mortality worldwide. There are well over 8,000 compounds present in tobacco and tobacco smoke, but we do not know what effect, if any, many of them have on smokers. Major interest has been on nicotine, as well as on toxic and carcinogenic effects and several major and minor components of tobacco smoke responsible for the negative health effects of smoking have been elucidated. Smokers themselves report a variety of positive effects from smoking, including effects on depression, anxiety and mental acuity. Smoking has also been shown to have protective effects in Parkinson's Disease. Are the subjective reports of a positive effect of smoking due to nicotine, of some other components of tobacco smoke, or are they a manifestation of the relief from nicotine withdrawal symptoms that smoking provides? This mini-review summarises what is currently known about the components of tobacco smoke with potential to have positive effects on smokers.