Current Bioactive Compounds - Volume 8, Issue 2, 2012

Epoxycarotenoids form a family of about 200 natural pigments present in photosynthetic organisms, fungi, and animal and human tissues. Numerous studies have evidenced that they exert strong antiproliferative, cytotoxic and proapoptotic activities in cancer cells grown in vitro, and that some of them are resorbed per os, suggesting that they may prevent cancer in vivo. This paper presents a comprehensive description of epoxycarotenoids reported up to 2011 (chemical structure, natural sources, human and animal absorption studies, physiological metabolites) and reviews their biological activity in cancer cells grown in vitro (antiproliferative, cytotoxic and pro-apoptotic activities; molecular and pharmacological targets, ability to reverse multidrug resistance, anti-angiogenic activity).

Several studies have provided evidence that the ployphenol curcumin can influence immune responses significantly. Here we overview the effects of curcumin in physiological and in pathological immune responses, including the recent findings from the use of curcumin to modulate immune-mediated diseases.

Foods enriched in β-glucans including oat and edible fungi as well as some purified β-glucans have been shown to reduce atherosclerotic lesions. The multiple mechanisms may be involved to affect several aspects of the pathogenesis of atherosclerosis such as phagocytosis of macrophages, NO production, epithelial cell functions and blood levels of cholesterol. Structurally different β-glucans may have different effects in the pathogenesis of atherosclerosis. The study of structure-function relationship may provide an approach for optimizing β-glucans to be used in the prevention of atherosclerosis.

The biotransformations of artemisinin and artemisinin derivatives leading to metabolites that may serve as prospective candidates for antimalarial evaluation or as starting materials for hemisynthesis of antimalarial derivatives are reviewed, focusing on the preparation of regio- and stereoselectively hydroxylated derivatives still possessing the 1,2,4- trioxane structure that can be used as scaffolds for the production of novel antimalarials with increased water solubility, lower toxicity and decreased potential for resistance. A special emphasis has been also placed on the recent manufacturing of artemisinin and derivatives via microbiological methods, involving cloning and overexpression of biosynthetic enzymes and allowing to design an alternative route for artemisinin production.

Ginseng, an ancient and famous herbal drug in oriental traditional medicine, has been used as a valuable tonic and for the treatment of various diseases. In medicinal purpose, ginseng root is used more common than aerial parts such as leaves and flower buds although extracts from ginseng aerial parts also contain similar active ingredients having pharmacological functions. This article reviews the purification of thirty four ginsenosides (1-34) from ginseng leaves and flower buds and their pharmacological effects. Ginsenosides are structurally classified into protopanaxadiol (PPD) and protopanaxatriol (PPT) types depending on their aglycones. The anti-oxidant activity of PPD-type ginsenosides like Rb1, Rd, Rc, and Rh2 was more active than that of PPT-type ginsenosides. Moreover, the presence of hydroperoxy in ginsenoside molecule was important for the intracellular reactive oxygen species (ROS) scavenging activity of ginsenosides. It became evident that ginsenoside F1 (8), ginsenoside F5 (9) and floralginsenoside Ta (21) remarkably inhibited the growth of HL-60 cells via the apoptosis pathway. Ginsenoside I (33) displayed potent inhibitory effect on IL-12 p40 production in lipopolysaccharide (LPS)-stimulated bone marrow-derived dendritic cells (BMDCs) with IC50 of 6.7 μM although floralginsenoside Kc (20) and floralginsenoside J (29) showed moderate effects. Ginsenoside F1 (8), a major ginsenoside of ginseng leaves, and notoginsenosie R1 (5) significantly decreased contraction by 35 ± 3.4% and by 53 ± 1.1% at 10 μM, respectively. Floralginsenoside Kc (20), a new ginsenoside from flower-buds, showed positive inotropic effect.

LASSBio-542 is a thalidomide analog synthesized as a 2-phenoxy-phthalimide derivative with the ability to inhibit Tumor Necrosis Factor-alpha (TNFα), behaving similarly in some instances to the original drug in vitro and in animal models. In new experiments comparing the biological activities of both drugs, we identified LASSBio-542 as an immunomodulator compound with extra properties dissimilar to those of thalidomide. While the extent of TNFα, IL-12p40 and IL-1β production stimulated by Lipopolysaccharide (LPS) inhibition was similar to thalidomide, Interleukin(IL)-10 production was inhibited by LASSBio-542; and Nuclear Factor kappa-B (NFκB) activation via proinflammatory stimulus was also inhibited by both drugs. In the same vein, angiogenesis was impaired while endothelial cell migration was affected by LASSBio-542 alone. Modulation of pro-angiogenic factors induced by TNFα in Human Umbilical Endothelial Vein Cells (HUVEC) such as IL-8, Vascular Endothelial Growth Factor-A (VEGF-A), Cyclooxygenase-2(COX-2), and TNFα itself was also observed by semiquantitative real-time PCR. The study of this molecule may provide new insights into thalidomide mechanisms and new therapeutic options for diseases characterized by singular alterations in the cytokine networks and angiogenesis impairments.

2-Cyanoethanethioamide (1) reacted with α,β-unsaturated ketones 2a,b to afford the corresponding 2- thioxopyridine-3-carbonitrile derivatives 6a,b. The reactivity of the latter products towards various chemical reagents was studied to yield both thieno[2,3-b]pyridines 9a-r and 3-aminothieno[2,3-b]pyridine-2-carbohydrazides 10a,b which were used in turn, to prepare N-phenylmethylenethieno[2,3-b]pyridine-2-carbohydrazides 13a,bpyrido[3',2':4,5]thieno[3,2- d]pyrimidinones (15a,b,16a,b) and pyrido[3',2':4,5]thieno[3,2-d]triazinones 17a,b. Considering the data of IR,1H NMR, mass spectra and elemental analyses the chemical structures of the newly synthesized heterocyclic compounds were elucidated.