Metal-mediated reductive hydrodehalogenation of organic halides.

Synergism between natural products and antibiotics against infectious diseases

The search for limonoids started long back when scientists started looking for the factor responsible for bitterness in citrus which has negative impact on citrus fruit and juice industry worldwide. The term limonoids was derived from limonin, the first tetranortriterpenoid obtained from citrus bitter principles. Compounds belonging to this group have exhibited a range of biological activities like insecticidal, insect antifeedant and growth regulating activity on insects as well as antibacterial, antifungal, antimalarial, anticancer, antiviral and a number of other pharmacological activities on humans. Although hundreds of limonoids have been isolated from various plants but, their occurrence in the plant kingdom is confined to only plant families of order Rutales and that too more abundantly in Meliaceae and Rutaceae, and less frequently in Cneoraceae and Harrisonia sp. of Simaroubaceae. Limonoids are highly oxygenated, modified terpenoids with a prototypical structure either containing or derived from a precursor with a 4,4,8-trimethyl-17-furanylsteroid skeleton. All naturally occurring citrus limonoids contain a furan ring attached to the D-ring, at C-17, as well as oxygen containing functional groups at C-3, C-4, C-7, C-16 and C-17. The structural variations of limonoids found in Rutaceae are less than in Meliaceae and are generally limited to the modification of A and B rings, the limonoids of Meliaceae are more complex with very high degree of oxidation and rearrangement exhibited in the parent limonoid structure. To counter the problem of bitterness in citrus juice and products genetic engineering of citrus to maximize the formation of limonoid glucosides for reducing limonoid bitterness is the focus of recent and future research. Regarding the biological activities of limonoids the investigations are to be directed towards detailed characterization, quantification, and designing a simple as well as versatile synthetic route of apparently important limonoids. Extraction methods too should be optimized; evaluation and establishment of pharmaco-dynamic and kinetic principles, and structure activity relationships should be a key goal associated with limonoids so that they can be safely introduced in our arsenal of pharmaceuticals to safeguard the humanity from the wrath of disease and its discomfort.

Limonoids: Overview of significant bioactive triterpenes distributed in plants kingdom

Traditional medicine has been a fertile source for revealing novel lead molecules for modern drug discovery. In plants, terpenoids represent a chemical defense against environmental stress and provide a repair mechanism for wounds and injuries. Interestingly, effective ingredients in several plant-derived medicinal extracts are also terpenoid compounds of monoterpenoid, sesquiterpenoid, diterpenoid, triterpenoid and carotenoid groups. Inflammatory diseases and cancer are typical therapeutic indications of traditional medicines. Thus folk medicine supports the studies which have demonstrated that plant-derived terpenoid ingredients can suppress nuclear factor-κB (NF-κB) signaling, the major regulator in the pathogenesis of inflammatory diseases and cancer.We review the extensive literature on the different types of terpenoid molecules, totalling 43, which have been verified both inhibiting the NF-κB signaling and suppressing the process of inflammation and cancer. It seems that during evolution, plants have established a terpene-based host defense which also represents a cornucopia of effective therapeutic compounds for common human diseases.

Terpenoids: natural inhibitors of NF-κB signaling with anti-inflammatory and anticancer potential

Natural Science Foundation of China[30000213, 30370160, 30670214]; National Basic Research Program of China (973 Program)[2009CB522300]; Chinese Academy of Sciences

Meliaceous limonoids: chemistry and biological activities.

In the continuous search for antifungal compounds from plants, the hydroxycoumarin scopoletin (1) was isolated from seed kernels of Melia azedarach L. from which three other compounds, vanillin (2), 4-hydroxy-3-methoxycinnamaldehyde (3), and (±) pinoresinol (4), have also been isolated. Guided fractionation through autobiography on TLC using Fusarium verticillioides (Saccardo) Nirenberg as test organism led to the isolation of 1, which exhibited a minimum inhibitory concentration (MIC) of 1.50 mg/mL in the microbroth dilution method. Despite its own weak activity, when the coumarin was combined with the above-mentioned compounds, a strong enhancement of the antifungal effect was observed, even showing a complete inhibition in the growth of the pathogen when 1 was added at a concentration of up to 5% of its MIC value. The same level of effectiveness was observed when the synthetic antifungal agents Mancozeb and Carboxin were each combined with compounds 1−4, in which cases it became possible to decrease th...

Antifungal Synergistic Effect of Scopoletin, a Hydroxycoumarin Isolated from Melia azedarach L. Fruits

Extracts from different parts of Melia azedarach L. were studied as potential antifungal agents for selected phytopathogenic fungi. In a serial agar dilution method, hexanic and ethanolic extracts from fruit, seed kernels, and senescent leaves exhibited fungistatic activity against Aspergillus flavus,Diaporthe phaseolorum var. meridionales, Fusarium oxysporum, Fusarium solani, Fusarium verticillioides, and Sclerotinia sclerotiorum. Both hexanic extract from senescent leaves and ethanolic extract from seed kernel were highly effective on all tested fungi, with minimum inhibitory concentration (MIC) values ranging from 0.5 to 25 mg/mL and 0.5 to 5 mg/mL, respectively. In addition, all of the above-mentioned extracts showed fungicidal activity on these fungi, with ethanolic seed kernel extract being the most active. Three compounds displaying activity against F. verticillioides were isolated from the ethanolic seed kernel extract and were characterized as vanillin (1), 4-hydroxy-3-methoxycinnamaldehyde (2), and (+/-)-pinoresinol (3), with MICs of 0.6, 0.4, and 1.0 mg/mL, respectively. These compounds also showed a synergistic effect when combined in different concentrations, needing four times less concentration to reach complete inhibition in the growth of F. verticillioides.

Antifungal effects of different organic extracts from Melia azedarach L. on phytopathogenic fungi and their isolated active components.

Systematic fractionation of a fruit extract from Argentine Melia azedarach L., which was monitored by an insect antifeedant bioassay, led to the isolation of meliartenin, a limonoid antifeedant, which existed as a mixture of two interchangeable isomers. At 4 μg/cm2 and 1 μg/cm2, the isomeric mixture was as active as azadirachtin in strongly inhibiting the larval feeding of Epilachna paenulata Germ. (Coleoptera: Coccinellidae) and the polyphagous pest, Spodoptera eridania (Lepidoptera: Noctuidae), respectively.

Potent limonoid insect antifeedant from Melia azedarach.

Background Head louse infestation is difficult to control because of increasing lice resistance to synthetic pediculicidal drugs. Objective To test the activity of extract and oil obtained from fruits of Melia azedarach L. against the head louse Pediculus humanus capitis. Methods A filter paper diffusion bioassay was carried out in order to determine the pediculicidal and ovicidal activity of extract and oil from M azedarach L. fruits. Results Both vegetable products, tested either individually or in combinations, showed high levels of mortality on adult lice, with values ranging between 62.9% and 96.5%. The highest mortality rate was obtained with a combination of 20% ripe fruit extract with 10% ripe fruit oil. A formulation made with both extract and oil at 10% plus the addition of emulsifier and preserving agents showed 92.3% pediculicidal activity. The products were also successful in delaying or inhibiting nymph emergence, with the formulation being the most effective, with a complete inhibition of emergence. Limitations Because adult lice are sensitive to starvation and therefore control mortalities are often higher than 20% in tests with field specimens, the results may not reflect the direct effect of the extract. Conclusions These results demonstrate the possibility of using Melia products for controlling head lice, which are difficult to control because of their resistance to the currently used anti-louse agents.

Carlos G. Ferrayoli

Papers

Antifungal Synergistic Effect of Scopoletin, a Hydroxycoumarin Isolated from Melia azedarach L. Fruits

Antifungal effects of different organic extracts from Melia azedarach L. on phytopathogenic fungi and their isolated active components.

Potent limonoid insect antifeedant from Melia azedarach.

In vitro pediculicidal and ovicidal activity of an extract and oil from fruits of Melia azedarach L.

Validation of a chiral HPLC assay for (R)-salbutamol sulfate.