Current Bioactive Compounds - Volume 8, Issue 4, 2012

This review deals with nitrogen oxides (NO, NO2, N2O) and NO derivatives peroxynitrite, peroxynitrous acid and nitroxyl, in relation to therapeutic effects and toxicity. An important member is NO which plays a multiple role in physiological action. The derivatives formed from interactions with superoxide are powerful oxidants functioning in toxicity. Nitroxyl (HNO), a metabolite of hydroxamic acids and hydroxyurea, is involved in the mode of action. Antioxidant action is discussed, as well as cell signaling. A multifaceted approach to bioaction is recommended.

Leishmaniasis is among the neglected diseases that represent 90% of the world burden of morbidity. According to the WHO, there are 12 million people, mostly deeply impoverished who suffer from visceral leishmaniasis (VL). The drugs currently used for the treatment of human cutaneous and visceral leishmaniasis are toxic, have severe adverse reactions which limit their use, and have presented teratogenic and cardiotoxic effects and increasing resistance. Given this scenario, the search for new, accessible and effective drugs for the treatment of leishmaniasis is a priority. This review aims to provide an overview of selected phenolic compounds with antileishmanial activities that have been published from 2007 to the present. Natural source or efficient synthesis, biological assays and possible mechanisms of actions are also described. Five flavonoids, six chalcones and three polyphenols have shown a selective index (SI) equal or greater than 20 which places them with greater antileishmanial activity. Quercitrin (3), hispidulin (6), octa-acetylhyperoside (11a), biochanin A (13) and ageconyflavone C (14) showed a SI range between 19.5 and 100. Chalcones 31, 33, 41, 42 65 and 67 were the highest antileishmanial compounds. Polyphenols 74 and 85 showed an important selective index when tested on promastigotes (71.4) and amastigotes (36.5) of L major and axenic amastigotes of L. mexicana (20). Compound 83 has demonstrated a potent in vitro (19.7) and in vivo effect on Balb/c mice experimentally infected with L. amazonensis. A wide range of biological assays with several strains and different parasite forms, have identified promising compounds, but few of them are conducted to clinical trials. This restriction emphasizes the necessity to reach a consensus regarding in vitro and in vivo screening protocol to advance leading compounds to clinical trials.

The oil of black seed (Nigella sativa) has been used as a folk medicine to treat a number of physiological disorders such as epilepsy, gastric problems, allergic conditions and various hepato-biliary ailments. Despite being unaware of the underlying phenomena for the cure of these diseases, people especially in the Mediterranean region have been using this ancient herb since ages. Researches in the 20th century conducted with the aim of tracking molecular pathways of anti-oxidant and anti-inflammatory mechanisms disclosed a great deal of information pertaining to the structural-activity relationships. Rigorous studies revealed that the major active constituent of Nigella sativa oil (NSO) is Thymoquinone (THQ) which exerts the majority of pharmacological actions observed by the essential oil. Since then, a large number of investigator groups have identified numerous molecular pathways of almost all major diseases which can be cured by THQ. Being a phytochemical, THQ has a high lipophilicity which makes it a poorly soluble agent in aqueous fluids restricting its systemic bioavailability. Also, THQ is highly light and heat-sensitive which further complicates its successful formulation for drug delivery. This review thus offers an insight to adequately comprehend the large number of pharmacological actions along with general mechanisms and major molecular targets pertaining to THQ. Additionally, a section dealing with the application of nanotechnological approaches to appropriately deliver the drug to its intended site of action has been elaborated.

In the present investigation, several phenolics based structurally related compounds of steroidal and nonsteroidal skeletons were synthesized and tested for their modulatory effect on ornithine decarboxylase (ODC) activity, an enzyme overexpressed in cancer. Additionally, these compounds were also examined for radical scavenging action to establish a correlation with the cancer chemopreventive property. Our result suggests that the tested compounds possessed radical scavenging activity, for being the inherent property of the phenolics. 3-(3',4'5'-trimethoxyphenyl)-4,5,6- trimethoxyindan-1-one oxime (15) exhibited highest inhibition of enzyme activity (91%) followed by 1-(2,4- dibromophenyl)-3-[3-methoxyestra 1,3,5(10)-trien-17-acetate,2-yl]-2-propen-1-one (26) (85%), 2-Hydroxy, 3-(3',4',5'- trimethoxy phenyl)-4,5,6-trimethoxy ind-2-en-1-one (17) (80%), 1-(3,4-methylenedioxyphenyl)-3-(3,4,5- trimethoxyphenyl)-2-propen-1-one (13) (74%) and 1-(3-methoxy, 4-hydroxyphenyl)-3-[3-methoxyestra 1,3,5(10)-trien- 17-acetate, 2-yl]-2-propen-1-one (28)(67%). Furthermore, it was observed that 1-(3-Methoxy, 4- hydroxyphenyl)-3-[3- methoxyestra 1,3,5 (10)-trien-17-acetate, 2-yl]-2-propen-1-one (28) showed the highest scavenging effect (67%) in nitric oxide (NO) assay, whereas 1-(3-methylphenyl)-3-[3-methoxy, 17-hydroxyestra 1,3,5(10)-trien, 2-yl]-2-propen-1-one (25) showed maximum inhibition of radical formation in 2,2-diphenyl-1-picrylhydrazyl (DPPH) analysis. Most of these compounds possessed a 3,4,5- trimethoxyphenyl unit which might be inducing enzyme inhibition and scavenging radical formation which could be further investigated to establish the structure-activity relationship.

The aim of this work was to review the ability of NIR spectroscopy to determine different parameters in wines, especially volatile compounds in barrel aged red wines, which are the highest quality in the market. Moreover, in this work we reviewed studies on the use of near infrared spectroscopy to discriminate wines. In general, the results showed this spectroscopy technique can be used as a rapid tool to determine different parameters, such as volatile compounds, phenolic compounds, and classical parameters in wines. Furthermore, NIR spectroscopy can be utilized to classify different wines, quickly and cheaply, but it takes time for calibration and validation of the method. Therefore, this technique can be used to authenticate and analyze wines.

Ceramide, a derivative of sphingolipid breakdown products, acts as second messenger for multiple extracellular stimuli including growth factors, chemical agents, and environmental stresses. They have been shown to be crtically involved in various biological processes, including differentiation, senescence, cell-cycle arrest, proliferation, and apoptosis. Ceramide molecules form distinct domains in the cell membrane, which may serve to re-organize cellular receptors and signaling molecules. Because of their promising biological activities and applications, here we focus on: biosynthesis, existence, importance, and structure elucidation, as well as representative examples concerning their structure and activity.