Mosquito repellents based on a natural chromene analogue with longer duration of action than N,N-diethyl-meta-toluamide (DEET).

Mosquito repellents play a major role in reducing bites and therefore mitigating transmission of mosquito-borne diseases. There is concern by some about the reported neurotoxic effects of the popular repellent DEET. Also, a product with longer effective activity after application is needed. This paper describes the synthesis and repellent activity of (2,2 dimethyl-2H-chromen-5-yl)methanol, a derivative of chromene amide that is a compound from the plant Amyris texana . This compound is more potent and provides longer duration of protection than DEET against Aedes aegypti (L.), the primary vector that transmits pathogens causing yellow and dengue fevers in humans.

Triterpenoids and flavonoids from Cecropia schreberiana Miq. (Urticaceae).

Phytochemical investigation of the leaves of Cecropia schreberiana Miq. (Urticaceae) led to the isolation of four triterpenoids (1-4), three flavone C-glycosides (5-7), two flavan-3-ols (8, 9), two flavanolignans (10, 11), and two proanthocyanidins (12, 13). All compounds were isolated from C. schreberiana for the first time. This is the first report demonstrating the presence of arjunolic acid (4), cinchonain Ia (10), and cinchonain Ib (11) in the Urticaceae family. The occurrence of flavanolignans within the family Urticaceae supports the likelihood that such compounds are more common within the class Magnoliopsida than previously thought.

Labdane diterpenoids from Leonotis leonurus.

Three known (leoleorins A-C) and eight hitherto unknown (leoleorins D-J and 16-epi-leoleorin F) labdane diterpenoids, were isolated from leaves of Leonotis leonurus. The absolute configurations of leoleorins A and D were established by X-ray crystallographic analyses. In a competitive binding assay, all isolated compounds showed inhibition in excess of 50% at various CNS receptors. Leoleorin C showed moderate binding affinity (Ki=2.9 µM) for the Sigma 1 receptor.

Bis-spirolabdane diterpenoids from Leonotis nepetaefolia.

Ten new bis-spirolabdane diterpenoids, leonepetaefolins A-E (1, 3, 5, 7, 9) and 15-epi-leonepetaefolins A-E (2, 4, 6, 8, 10), together with eight known labdane diterpenoids (11-18) as well as two known flavonoids, apigenin and cirsiliol, were isolated from the leaves of Leonotis nepetaefolia. The structures of the new compounds were determined on the basis of 1D- and 2D-NMR experiments including (1)H, (13)C, DEPT, (1)H-(1)H COSY, HSQC, HMBC, and NOESY. The absolute configuration of an epimeric mixture of 1 and 2 was determined by X-ray crystallographic analysis. The compounds isolated were evaluated for their binding propensity in several CNS G-protein-coupled receptor assays in vitro.

Natural-product-based chromenes as a novel class of potential termiticides.

BACKGROUND: Among the termite infestations in the United States, the Formosan subterranean termite, Coptotermes formosanus Shiraki (Isoptera: Rhinotermitidae), is considered to be the most devastating termite pest. This pest most likely invaded North America as a result of the disembarkation of wooden military cargo at the port of New Orleans that arrived from Asia during and after World War II. It has now spread over other states, including Texas, Florida, South Carolina and California. Devastation caused by C. formosanus in North America has been estimated to cost $ US 1 billion a year. Over the past decades, organochlorines and organophosphates, the two prominent classes of termite control agents, have been banned owing to environmental and human health concerns. At the present time, phenylpyrazoles, pyrethroids, chloronicotinyls and pyrroles are being used as termite control agents. Mammalian toxicity and seeping of these compounds into groundwater are some of the drawbacks associated with these treatments. The instruction for the application of these termiticides indicate ground water advisory. Hence, with the increasing spread of termite infestation there is an increased need to discover effective, environmentally friendly and safe termite control agents with minimal mammalian toxicity. RESULTS: Chromene analogs derived from a natural-product-based chromene amide isolated from Amyris texana were tested in a collaborative discovery program for effective, environmentally friendly termite control agents. Several chromene derivatives were synthesized and characterized as a novel class of potential termiticides, followed by bioassays. These compounds exhibited significantly higher mortalities compared with untreated controls in laboratory bioassays. CONCLUSION: Chromene derivatives have been shown to be a potential novel class of termiticides against Formosan subterranean termites.

Labdane diterpenoids from Leonurus sibiricus.

Six new labdane diterpenoids, preleosibirone A (1), 13-epi-preleosibirone A (2), isopreleosibirone A (3), leosibirone A (4), leosibirone B (5), and 15-epi-leosibirone B (6), were isolated from the leaves of Leonurus sibiricus. The absolute configurations of 1, 2, 5, and 6 were established by X-ray crystallographic analyses, and leosibirone A (4) was shown to be an artifact of the isolation process.

Chemical constituents, antimicrobial and antimalarial activities of Zanthoxylum monophyllum.

From the leaves and bark of Zanthoxylum monophyllum, a new lignan, 3-methoxy-3',4'-methylenedioxylignan-4,8,9,9'-tetraol (1), has been isolated along with 22 known compounds (2- 23), fifteen of them reported for the first time from Z. monophyllum. Their chemical structures were elucidated using detailed spectroscopic studies and chemical analysis. All compounds were evaluated for antimicrobial and antiprotozoal activities. Alkaloids BIS-[6-(5,6-dihydro-chelerythrinyl)] ether (2) and 6-ethoxy-chelerythrine (4) exhibited strong activity against Aspergillus fumigatus and methicillin-resistant Staphylococcus aureus (MRSA). Compound 4-methoxy-N-methyl-2-quinolone (9) exhibited significant activity against MRSA (IC50 value of 8.0 µM) while compound 5,8,4'-trihydroxy-3,7,3'-trimethoxyflavone (10) showed weak activity against Plasmodium falciparum.

Antileishmanial Germacranolides from Calea zacatechichi.

Phytochemical study of the leaves and stems of Calea zacatechichi Schl. (Asteraceae) led to the isolation of a series of six germacranolides (1-6) with significant antileishmanial activity. The structure of a new compound named by us as calealactone D (1) was determined by NMR and MS, and its absolute configuration by X-ray crystallography. In addition, calealactone E (5) was discovered as a new naturally occurring compound, and the absolute configuration of calealactone C (2) was also determined by X-ray crystallography. All compounds were biologically evaluated in antimicrobial and antiprotozoal assays.

Xenobiotic biotransformation of 4-methoxy-N-methyl-2-quinolone, isolated from Zanthoxylum monophyllum.

Phytochemical evaluation of Zanthoxylum monophyllum has led to the isolation of the alkaloid 4-methoxy-N-methyl-2-quinolone (1) with a significant activity against methicillin-resistant Staphylococcus aureus (MRSA), with an IC50 value of 1.5 microg/mL. Xenobiotic biotransformation of 1 has been conducted with the general goal of increasing the bioactivity of the compound and contributing new leads for further pharmacological research. Twenty-nine microorganisms were used for screening and two (Aspergillus flavus and Cunninghamella echinulata var. echinulata) were able to transform compound 1 to 4-methoxy-2-quinolone (2). Structural identification of the compounds was based on NMR, IR, and MS data.

New class of algicidal compounds and fungicidal activities derived from a chromene amide of Amyris texana.

A chromene amide, N-[2-(2,2-dimethyl-2H-1-benzopyran-6-yl)ethyl]-N,3-dimethylbutanamide, was isolated from the EtOAc extract of the leaves of Amyris texana and found to have moderate antifungal activity against Colletotrichum spp. and selective algicidal activity against Planktothrix perornata, a cyanobacterium (blue-green alga) that causes musty off-flavor in farm-raised channel catfish (Ictalurus punctatus). To improve the selective algicidal activity and provide water solubility, a series of chromene analogues were synthesized and evaluated for algicidal activity using a 96-well microplate rapid bioassay. In addition, the chromene analogues were evaluated for antifungal and phytotoxic activities. Hydrochloride salts of a chromene amine analogue showed improved water solubility and selectivity toward P. perornata with activity comparable to that of the naturally occurring chromene amide.

Estimation of treatment time for microbial preprocessing of biomass.

Biochemical conversion of lignocellulosic biomass to ethanol involves size reduction, preprocessing, pretreatment, enzyme hydrolysis, and fermentation. In recent years, microbial preprocessing has been gaining attention as a means to produce labile biomass for lessening the requirement of pretreatment severity. However, loss of sugars due to microbial consumption is a major consequence, suggesting its minimization through optimization of nutrients, temperature, and preprocessing time. In this work, we emphasized estimation of fungal preprocessing time, at which higher sugar yields can be achieved after preprocessing and enzyme hydrolysis. The estimation is based on the enzymatic activity profile obtained by treating switchgrass with Phanerochaete chrysosporium for 28 days. Enzyme assays were conducted once in every 7 days for 28 days, for activities of phenol oxidase, peroxidase, beta-glucosidase, beta-xylosidase, and cellobiohydrolase. We found no activity for phenol oxidase and peroxidase, but the greatest activities for cellulases on the seventh day. We then treated switchgrass for 7 days with P. chrysosporium and observed that the preprocessed switchgrass had higher glucan (39%), xylan (17.5%), and total sugar yields (25.5%) than the unpreprocessed switchgrass (34%, 37.5%, and 20.5%, respectively, p < 0.05). This verifies the utility of using enzyme assays for initial estimation of preprocessing time to enhance sugar yields.

Algicide constituents from Swinglea glutinosa.

Oscillatoria perornata, a cyanobacterium (blue-green alga), common in catfish production ponds in the southeastern United States, produces the monoterpene 2-methylisoborneol (MIB), which is absorbed into catfish flesh and imparts a "musty" taste, rendering them unpalatable and unmarketable. Algicides that are currently in the commercial market to control O. perornata have broad-spectrum toxicity toward other beneficial phytoplankton, such as the green alga Selenastrum capricornutum, as well as low biodegradability. As part of our continuing efforts to search for natural-product-based algicides, the ethyl acetate extract of the roots of Swinglea glutinosa was investigated. This report describes isolation and structure elucidation of one novel coumarin, two known coumarins, and nine acridone alkaloids from S. glutinosa root extracts and the evaluation of these compounds for algicidal activity against O. perornata.

Alkamides from the leaves of Zanthoxylum syncarpum.

Three alkamides (1-3) were isolated from the leaves of Zanthoxylum syncarpum. The structures of the new compounds 1 and 2 were established by spectroscopic data and chemical conversion, and by the X-ray crystallography of 1. Compound 3, the racemic form of the known compound syncarpamide, showed moderate antiplasmodial activity, with IC50 values of 4.2 and 6.1 microM against Plasmodium falciparum D6 clone and W2 clone, respectively.

Syncarpamide, a new antiplasmodial (+)-norepinephrine derivative from Zanthoxylum syncarpum.

A new (+)-norepinephrine derivative, syncarpamide (1), along with a known coumarin, (+)-S-marmesin (2), and one known alkaloid, decarine (3), have been isolated from the stem of Zanthoxylum syncarpum. The structure of compound 1 was elucidated on the basis of 1D and 2D NMR, MS, IR, optical rotation, and CD analyses. Its absolute stereochemistry was elucidated by synthesis of its enantiomer and subsequent comparison of CD data. Characterizations of compounds 2 and 3 were based on spectral analysis and comparison with reported data. Compounds 1 and 3 showed antiplasmodial activity, with IC(50) values of 2.04 and 1.44 microM against Plasmodium falciparum D(6) clone and 3.06 and 0.88 microM against P. falciparum W(2) clone, respectively. Compound 3 showed cytotoxicity at 56.42 microM, whereas compound 1 was not cytotoxic at 10.42 microM. Compound 1 was tested for hypotensive activity, but no activity was observed. Compound 2 showed no antiplasmodial or antimicrobial activities.

Phenolic compounds from Nymphaea odorata.

Assay-guided fractionation of the ethanol extract of Nymphaea odorata resulted in the identification of two lignans, one new (1) and one known (2), together with six known flavonol glycosides (3-8). The structures of 1-8 were established by spectroscopic analysis as nymphaeoside A (1), icariside E(4) (2), kaempferol 3-O-alpha-l-rhamnopyranoside (afzelin, 3), quercetin 3-O-alpha-l-rhamnopyranoside (4), myricetin 3-O-alpha-l-rhamnopyranoside (myricitrin, 5), quercetin 3-O-(6' '-O-acetyl)-beta-d-galactopyranoside (6), myricetin 3-O-beta-d-galactopyranoside (7), and myricetin 3-O-(6' '-O-acetyl)-beta-d-galactopyranoside (8). Compounds 3, 4, and 7 showed marginal inhibitory effect against fatty acid synthase with IC(50) values of 45, 50, and 25 microg/mL, respectively.

Flavonoids with activity against methicillin-resistant Staphylococcus aureus from Dalea scandens var. paucifolia.

Bioassay-guided fractionation of the ethyl acetate extract of the roots of Dalea scandens (Miller) R. Clausen var. paucifolia led to the isolation of new flavonoids, 2( S)-5'-(-1"',1"'-dimethylallyl)-8-(3",3"-dimethylallyl)-2',4',5,7-tetrahydroxyflavanone, 2( S)-5'-(1"',1"'-dimethylallyl)-8-(3",3"-dimethylallyl)-2'-methoxy-4',5,7-trihydroxyflavanone and 5'-(1"',1"'-dimethylallyl)-8-(3",3"-dimethylallyl)-2',4',5,7-tetrahydroxyflavone. Structure elucidation was carried out by spectroscopic methods. All three compounds showed significant activity against both methicillin-susceptible and methicillin-resistant Staphylococcus aureus.

Evaluation of Podophyllum peltatum accessions for podophyllotoxin production.

In an effort to develop a sustainable source of podophyllotoxin for the production of anticancer drugs such as etoposide, teniposide and etopophos, Podophyllum peltatum accessions with podophyllotoxin-rich leaf biomass were identified and transplanted to different growing conditions by vegetative cuttings. Results indicate that the lignan profile in leaves does not change over time or due to environment conditions. Podophyllotoxin and alpha-peltatin content in the blades seems to be stable with an inverse relationship of concentration between these compounds. A podophyllotoxin-rich leaf accession showed low biosynthetic capability to synthesize alpha- and beta-peltatin and the converse was also true, indicating that selection and cultivation of high-yielding podophyllotoxin leaf biomass may reduce production costs.