NF-kappaB is a ubiquitous and well-characterised protein responsible for the regulation of complex phenomena, with a pivotal role in controlling cell signalling in the body under certain physiological and pathological conditions. Among other functions, NF-kappaB controls the expression of genes encoding the pro-inflammatory cytokines (e. g., IL-1, IL-2, IL-6, TNF-alpha, etc.), chemokines (e. g., IL-8, MIP-1alpha, MCP1, RANTES, eotaxin, etc.), adhesion molecules (e. g., ICAM, VCAM, E-selectin), inducible enzymes (COX-2 and iNOS), growth factors, some of the acute phase proteins, and immune receptors, all of which play critical roles in controlling most inflammatory processes. Since NF-kappaB represents an important and very attractive therapeutic target for drugs to treat many inflammatory diseases, including arthritis, asthma, and the auto-immune diseases, most attention has been paid in the last decade to the identification of compounds that selectively interfere with this pathway. Recently, a great number of plant-derived substances have been evaluated as possible inhibitors of the NF-kappaB pathway. These include a wide range of compound classess, such as lignans (manassantins, (+)-saucernetin, (-)-saucerneol methyl ether), sesquiterpenes (costunolide, parthenolide, celastrol, celaphanol A), diterpenes (excisanin, kamebakaurin), triterpenes (avicin, oleandrin), polyphenols (resveratrol, epigallocatechin gallate, quercetin), etc. In this mini-review we will discuss the medicinal chemistry of these compounds with regards to the NF-kappaB inhibition.

Tubulin protein is a major target for anticancer drug discovery. As a result, antimitotic agents constitute an important class of the current anticancer drugs. Hundreds of tubulin inhibitors, naturally occurring, semisynthetic or synthetic, have been reported. Among these, combretastatin A-4 (CA-4), isolated from a South African tree Combretum caffrum, is one of the most potent antimitotic agents. CA-4 shows strong cytotoxicity against a variety of cancer cells, including multi-drug resistant cancer cell lines. It has also been demonstrated to exert highly selective effects in proliferating endothelial cells. CA-4 disodium phosphate (CA4DP), a water-soluble prodrug of CA-4, shows potent antivascular and antitumor effects in a wide variety of preclinical tumor models. Consequently, a number of CA-4 analogues has been synthesized and evaluated. In this paper, the structure-activity relationships and pharmacological properties of the CA-4 derivatives as a class of potent antimitotic anticancer agents are reviewed and discussed.

No abstract

Two new furo-1,2-naphthoquinones, crataequinones A (1) and B (2), were isolated from the fruits of Crataegus pinnatifida. The structures of two new compounds were determined as 11,12-dimethoxy-3,4-furo-1,2-naphthoquinone (1) and 11,12-dimethoxy-5-hydroxy-3,4-furo-1,2-naphthoquinone (2) by spectroscopic analysis. The two compounds 1 and 2 showed significant inhibitory activity with IC50 values of 33 and 90 microM, respectively, against the expression of intercellular adhesion molecule-1 (ICAM-1).

No abstract