The biochemistry and medical significance of the flavonoids.

https://chemistry.mdma.ch/hiveboard/rhodium/pdf/piper.phytochemistry.pdf

Phytochemistry of the genus Piper

A review of botanical phytochemicals with mosquitocidal potential.

Gene expression signature-based chemical genomic prediction identifies a novel class of HSP90 pathway modulators

In vitro antiplasmodial activity of medicinal plants native to or naturalised in South Africa.

Extracts of 22 species of Meliaceae were examined for antimalarial activity using in vitro tests with two clones of Plasmodium falciparum, one sensitive to chloroquine (W2) and one chloroquine-resistant (D6). Twelve extracts were found to have activity, including extracts of Cedrela odorata wood and Azadirachta indica leaves, which contained the limonoid gedunin. These extracts were more effective against the W2 clone than the D6 clone, suggesting there is no cross-resistance to chloroquine. Gedunin was extracted in quantity, and nine derivatives prepared for a structure-activity study, which revealed essential functionalities for activity. The study also included four other limonoids derived from related Meliaceae. Only gedunin had better activity than chloroquine against the W2 clone. This active principle could be used to standardize a popular crude drug based on traditional use of A. indica in West Africa.

Antimalarial Activity of Tropical Meliaceae Extracts and Gedunin Derivatives

2,3-Dihydro-2-(4'-hydroxyphenyl)-3-methyl-5(E)-propenylbenzofuran (conocarpan) (1), 2-(4'-hydroxy-3'-methoxyphenyl)-3-methyl-5(E)- propenylbenzofuran (eupomatenoid-5) (2), and 2-(4'- hydroxyphenyl)-3-methyl-5(E)-propenylbenzofuran (eupomatenoid-6) (3), three known neolignans found for the first time in a species of the Piperaceae, were isolated from Piper decurrens via insecticidal bioassay-guided fractionation, along with a small quantity of a new related compound, 2,3-dihydro-5-formyl-2-(4'-hydroxyphenyl)-3-methylbenzofuran (decurrenal) (4), and 3,7,11,15-tetramethyl-2(E)-hexadecen-1-ol (trans-phytol).

Insecticidal Neolignans from Piper decurrens

A quantitative ethnobotanical approach to antimalarial drug discovery led to the identification of Lansium domesticum Corr. Ser. (Meliaceae) as an important antimalarial used by Kenyah Dyak healers in Indonesian Borneo. Triterpenoid lansiolides with antimalarial activity were isolated from the bark and shown to have activity in both in vitro bioassays with Plasmodium falciparum, and in mice infected with P. berghei. A survey of African and tropical American Meliaceae led to further development of the limonoid gedunin from the traditionally used medicinal plants, tropical cedar, Cedrela odorata L., and neem, Azadirachta indica A. Juss. Gedunin has significant in vitro activity but initially showed poor in vivo activity. In vivo activity was improved by (1) incorporation into an easy to absorb suspension, (2) preparation of a more stable compound, 7-methoxygedunin; and (3) synergism with dillapiol, a cytochrome P450 3A4 inhibitor. The results show the potential for both antimalarial drug and phytomedicine development from traditionally used plants.

Traditionally-used antimalarials from the Meliaceae.

Gas chromatography analysis of the essential oils of leaves and bark collected from the newly discovered tree Pleodendron costaricense identified alpha-pinene, beta-pinene, beta-myrcene, beta-thujene, and beta-caryophyllene as their major constituents. Phytochemical analysis of P. costaricense parts led to the isolation and identification of delta-tocotrienol, beta-sitosterol, four known drimane-type sesquiterpenes, cinnamodial (1), cinnamosmolide (2), polygodial (3), and mukaadial (4), and two new compounds, a drimane-type sesquiterpene, parritadial (5), and an eremophilane-type sesquiterpene, pleodendione (6). Antifungal assays with the two major compounds, 1 and 2, were carried out, and results showed a high activity of 1 against Alternaria alternata (MIC = 3.9 microg/mL), Candida albicans azole-resistant strain D10, and Wangiella dermatitides (MICs = 15.6 microg/mL). Compound 2 showed less potent antifungal activities than 1 but was more effective against Candida albicans azole-resistant strain CN1A (MIC = 23.4 microg/mL) and Pseudallescheria boydii (MIC = 78.1 microg/mL). A combination of the dialdehyde sesquiterpenes with dillapiol showed a synergistic antifungal effect with 1 and an additive effect with 4 and 5.

Phytochemistry and antifungal properties of the newly discovered tree Pleodendron costaricense.

XThe CHCl3-soluble extract of Piper guanacastensis (Piperaceae) was found to have noteworthy insecticidal activity to Aedes atropalpus mosquito larvae (LC50 80.5 Ig/mL). Bioassay-guided fractionation afforded methyl 4-hydroxy-3-(3′-methyl-2′-butenyl)benzoate (1) as the major bioactive constituent (LC50 20.5 Ig/mL). The separation of compound 1 from its transesterification artifact (2), ethyl 4-hydroxy-3-(3′-methyl-2′-butenyl)benzoate, was achieved by recycling reversed-phase HPLC. The flavonoids acacetin, chrysin, and pinostrobin were also isolated from the active fraction but did not display insecticidal properties. The Piperaceae or pepper family is widely used in tropical regions throughout the world as medicines, condiments in regional cuisine, and pest-control agents. 1 As a part of a program aimed at the development of potentially useful phytochemicals as insect control agents (“green insecticides”) and because of our interest in the chemical ecology of the American neotropical Piperaceae, we now report the isolation and identification of a novel prenylated phenolic from Piper guanacastensis C. DC., an endemic species of Costa Rica in Central America. The insecticidal and growth-reducing properties of this plant material, as well as the activity of 13 additional species in the Piperaceae, were established previously using as model insect the European corn borerOstrinia nubilalis(Lepidoptera: Pyralidae). 2 This investigation confirmed that tropical American Piper species, including P. guanacastensis, have insecticidal activities comparable to previously studied African and Asian species. Bioactivity-guided fractionation of selected active crude extracts indicated the importance of phenyl propanoids (Piper aduncum), amides (Piper tuberculatum), and lignans (Piper decurrens) as the chemical defenses of the Piperaceae. 2,3 In the present study, the EtOH extract of P. guanacastensis aerial parts was found to be toxic to mosquito larvae, Aedes atropalpus L. (Diptera: Culicidae), the model insect used during bioactivity-guided fractionation of the crude total extract (LC50 ) 127.5 Ig/mL) for isolation of the active principle. The insecticidal activity was traced to the CHCl3-soluble fraction. Further fractionation on a silica gel column yielded a fraction rich in a mixture of prenylated benzoic acids derivatives, which had most of the insecticidal activity. HPLC separation furnished esters 1 (LC50 ) 20.5 Ig/ mL) and 2 (LC50 ) 25.7 Ig/mL) in pure form as the major active components. The structure of compound 1 was elucidated as methyl 4-hydroxy-3-(3′-methyl-2′butenyl)benzoate on the basis of spectral analysis. Derivative2represents the ethyl ester analog of natural product1and, therefore, an artifact of extraction formed by prolonged storage of the plant material in EtOH. The flavonoids acacetin, chrysin, and pinostrobin were also isolated from the CHCl3-soluble fraction but did not have pronounced insecticidal activity. These compounds have been found in other medicinally important Piper species, especially in those native to the Middle and Far East. 4

http://repositorio.fciencias.unam.mx:8080/xmlui/bitstream/handle/11154/2882/Methyl%204-hydroxy-3-(3'-methyl-2'-butenyl)benzoate,%20major%20insecticidal%20principle%20from%20Piper%20guanacastensis.pdf?sequence=2

T. Durst

Papers

Antimalarial Activity of Tropical Meliaceae Extracts and Gedunin Derivatives

Insecticidal Neolignans from Piper decurrens

Traditionally-used antimalarials from the Meliaceae.

Phytochemistry and antifungal properties of the newly discovered tree Pleodendron costaricense.

Methyl 4-Hydroxy-3-(3'-methyl-2'-butenyl)benzoate, Major Insecticidal Principle from Piper guanacastensis