Evaluation of naturally occurring curcuminoids and related compounds against mosquito larvae.

The three curcuminoid components commonly isolated from Curcuma longa, curcumin (1), demethoxycurcumin (2), and bis-demethoxycurcumin (3) were separated and isolated from a commercially available turmeric extract product in high purity and sufficient amounts. Three more derivatives of curcumin, the di-O-demethylcurcumin (4), di-O-methylcurcumin (5) and the di-O-acetylcurcumin (6) were also synthesized and characterized. All six compounds were evaluated for their larvicidal effect against the mosquito Culex pipiens. Curcumin (1) exhibited highly potent larvicidal activity with LC(50) value of 19.07mgL(-1). Moreover, di-O-demethylcurcumin (4), was found to be equally active with LC(50) value of 12.42mgL(-1). Based on the LC(90) values of the two compounds, di-O-demethylcurcumin (4) was the most active of all, resulting in an LC(90) value of 29.40mgL(-1), almost half of the LC(90) value 61.63mgL(-1) found for compound 1. The rest of the compounds were inactive at concentrations even as high as 150mgL(-1) indicating a dependence of the larvicidal activity upon the substitution patent and the presence of aromatic hydroxyl and methoxy moieties. These results show for the first time the potential of this valuable natural product regarding its use as vector control agent.

Stabilization of microtubules by Combretastatin D derivatives.

The effect of five derivatives of Combretastatin D on tubulin polymerization was investigated. All of them were found to stabilize microtubules to various degrees. The derivatives bearing polar substituents were found to be the most active.

Inhibition of topoisomerase I by naphthoquinone derivatives.

Alkannin and shikonin are naturally occurring naphthoquinones. We have tested several derivatives of the title compounds and we have found that naphthoquinones bearing at least one phenolic hydroxyl group are potent inhibitors of topoisomerase I. The ability of the tested compounds to complex Zn++ parallels with a few exceptions their topoisomerase I inhibition properties while their intercalation and redox properties do not.

Total synthesis of taxol.

Taxol, a substance originally isolated from the Pacific yew tree (Taxus brevifolia) more than two decades ago, has recently been approved for the clinical treatment of cancer patients. Hailed as having provided one of the most significant advances in cancer therapy, this molecule exerts its anticancer activity by inhibiting mitosis through enhancement of the polymerization of tubulin and consequent stabilization of microtubules. The scarcity of taxol and the ecological impact of harvesting it have prompted extension searches for alternative sources including semisynthesis, cellular culture production and chemical synthesis. The latter has been attempted for almost two decades, but these attempts have been thwarted by the magnitude of the synthetic challenge. Here we report the total synthesis of taxol by a convergent strategy, which opens a chemical pathway for the production of both the natural product itself and a variety of designed taxoids.

Synthesis and antimicrobial properties of 2H-pyran-3(6H)-one derivatives and related compounds.

The synthesis of several derivatives of 2H-pyran-3(6H)-ones and their Michael adducts is described. Phenylthio, benzenesulfonyl, p-acetylaminobenzenesulfonyl, and p-bromophenyl substituents are beneficial for activity against gram-positive bacteria. 2-[4-(Phenylthio)phenyl]-2-methyl-6-methoxy-2H-pyran-3(6H)-one (8a) showed a minimum inhibitory concentration of 1.56 micrograms/mL against Staphylococcus aureus ATCC 2593, and 2-[4-(phenylthio)phenyl]-2-methyl-6-[(p-nitrobenzoyl)oxy]-2H-pyran-3 (6H)-one (9) showed a minimum inhibitory concentration of 0.75 microgram/mL against Streptococcus sp. C203M. In general, derivatives of 6-hydroxy-2H-pyran-3(6H)-ones with substituents at C-2 and C-6 showed significant activity against gram-positive bacteria. More specifically, the bulkier the C-2 substituent, the greater the antibacterial activity. Michael adducts of thiols (13) showed activity, which may be due to a retro-Michael reaction. In conclusion, the alpha,beta-enone system is essential for the activity of 6-hydroxy-2H-pyran-3(6H)-ones, and the size and nature of substituents at C-2 are associated with antimicrobial activity.