Tony Durst

Insecticidal defenses of Piperaceae from the neotropics.

Insecticidal and growth-reducing properties of extracts of 14 species of American neotropical Piperaceae were investigated by inclusion in diets of a polyphagous lepidopteran, the European corn borer,Ostrinia nubilalis. Nutritional indices suggested most extracts acted by postdigestive toxicity.Piper aduncum, P. tuberculatum, andP. decurrens were among the most active species and were subjected to bioassay-guided isolation of the active components. Dillapiol was isolated from the active fraction ofP. aduncum, piperlonguminine was isolated fromP. tuberculatum, and a novel neolignan fromP. decurrens. The results support other studies on Asian and AfricanPiper species, which suggest that lignans and isobutyl amides are the active defence compounds in this family.

Bioassay‐guided fractionation of lemon balm (Melissa officinalis L.) using an in vitro measure of GABA transaminase activity

A novel pharmacological mechanism of action for the anxiolytic botanical Melissa officinalis L. (lemon balm) is reported. The methanol extract was identified as a potent in vitro inhibitor of rat brain GABA transaminase (GABA‐T), an enzyme target in the therapy of anxiety, epilepsy and related neurological disorders. Bioassay‐guided fractionation led to the identification and isolation of rosmarinic acid (RA) and the triterpenoids, ursolic acid (UA) and oleanolic acid (OA) as active principles. Phytochemical characterization of the crude extract determined RA as the major compound responsible for activity (40% inhibition at 100 µg/mL) since it represented approximately 1.5% of the dry mass of the leaves. Synergistic effects may also play a role. Copyright

Insecticidal activity of Piper tuberculatum Jacq. extracts: synergistic interaction of piperamides

Abstract 1  The insecticidal activity of the neotropical pepper Piper tuberculatum Jacq. and its isolated piperamides was studied. Bioassays with the mosquito Aedes atropalpus L. assessed the relative toxicity of the whole extract of Piper tuberculatum and four of the piperamides, which were isolated and identified, then prepared synthetically. 2  The results confirm that P. tuberculatum leaf extracts are as effective as black pepper seed extract and provide an alternative pepper insecticide from a more convenient source, the leaves. 3  Experiments with piperamides showed that the tertiary and quaternary mixtures have greater‐than‐additive toxicity compared to single compounds or binary mixtures. One of the four amide compounds, 4,5‐dihydropiperlonguminine, was the most acutely toxic in mosquito larvae bioassays. 4  A study of piperamide levels from different P. tuberculatum populations in Costa Rica determined that they were relatively homogeneous. Piper tuberculatum from only one of the five sites had higher levels of one piperamide, 4,5‐dihydropiperine, in both leaf and stem parts. One explanation for differences in the amide concentrations between populations is that one site is ecologically unique compared to the other four.

Traditionally-Used Antimalarials from the Meliaceae

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.

Reaction of (R)-pantolactone esters of alpha-bromoacids with amines a remarkable synthesis of optically active alpha-amino esters

(R)-Pantolactone esters of racemic α-bromo acids react with amines to give α-amino esters having the (S)-configuration at the α-carbon in yields which are considerably greater than the 50% expected on the basis of a simple SN2 displacement reaction.

Preparation of optically active stilbene oxides via sulfonium salts derived from C2 symmetric thiolanes.

Abstract Trans-stilbene oxides have been obtained in up to 83% enantiomeric excess via reaction of S-benzyl ylides prepared from optically active trans-2,5-disubstituted thiolanes.

Multiple modes of insecticidal action of three classes of polyacetylene derivatives from Rudbeckia hirta

Polyacetylene derivatives (PADs) occurring in Rudbeckia hirta (Asteraceae) were isolated or chemically synthesized and examined for their insecticidal properties against mosquito larvae under different light regimes: dark (D), visible (VIS) and visible+near-ultra-violet (VIS+UV). A straight chain polyine, 1-tridecene-3,5,7,9,11-pentayne, was highly toxic under all light regimes tested although a thiarubrine, 3-(1-propynyl)-6-(3,5-hexadien-1-ynyl)-1,2-dithiacyclohexa-3,5-diene, and a thiophene, 2-(1-propynyl)-5-(3,5-hexadien-1-ynyl)-thiophene, showed a toxicity that significantly varied between the light regimes. The thiarubrine was more toxic against mosquito larvae under D or VIS+UV conditions while the thiophene had a more pronounced toxicity only in presence of VIS+UV irradiation. The distinctive insecticidal properties in darkness of the thiarubrine compare to the thiophene were also confirmed in trials with larvae of a herbivorous insect, Manduca sexta. Such a variability in the light-modulated toxicity to insects for different biosynthetically related PADs emphasizes a diversity in the insecticidal mechanisms of action.

Asymmetric synthesis of alpha-halo esters

Abstract The reaction of (R)-Pantolactone with α-halogenated ketenes has been found to proceed with good to excellent diastereoselectivities (de 75 to > 95%). The (R)-Pantolacto chiral auxiliary induced the (S)-configuration at the new chiral center in most cases.

Effects of oral exposure to naturally-occurring and synthetic deoxynivalenol congeners on proinflammatory cytokine and chemokine mRNA expression in the mouse

The foodborne mycotoxin deoxynivalenol (DON) induces a ribotoxic stress response in mononuclear phagocytes that mediate aberrant multi-organ upregulation of TNF-α, interleukins and chemokines in experimental animals. While other DON congeners also exist as food contaminants or pharmacologically-active derivatives, it is not known how these compounds affect expression of these cytokine genes in vivo. To address this gap, we compared in mice the acute effects of oral DON exposure to that of seven relevant congeners on splenic expression of representative cytokine mRNAs after 2 and 6h. Congeners included the 8-ketotrichothecenes 3-acetyldeoxynivalenol (3-ADON), 15-acetyldeoxynivalenol (15-ADON), fusarenon X (FX), nivalenol (NIV), the plant metabolite DON-3-glucoside (D3G) and two synthetic DON derivatives with novel satiety-inducing properties (EN139528 and EN139544). DON markedly induced transient upregulation of TNF-α IL-1β, IL-6, CXCL-2, CCL-2 and CCL-7 mRNA expressions. The two ADONs also evoked mRNA expression of these genes but to a relatively lesser extent. FX induced more persistent responses than the other DON congeners and, compared to DON, was: 1) more potent in inducing IL-1β mRNA, 2) approximately equipotent in the induction of TNF-α and CCL-2 mRNAs, and 3) less potent at upregulating IL-6, CXCL-2, and CCL-2 mRNAs. EN139528s effects were similar to NIV, the least potent 8-ketotrichothecene, while D3G and EN139544 were largely incapable of eliciting cytokine or chemokine mRNA responses. Taken together, the results presented herein provide important new insights into the potential of naturally-occurring and synthetic DON congeners to elicit aberrant mRNA upregulation of cytokines associated with acute and chronic trichothecene toxicity.

Singlet oxygen photosensitizing properties of bithiophene and terthiophene derivatives

Abstract An extensive set of thiophene intervals has been evaluated to determined their sensitized quantum yields for singlet oxygen generation in solution. The values have been determined using laser excitation and time-resolved detection of the near-IR phosphorescence from singlet oxygen. Values determined in this work, cited in earlier publications and thesis dissertations, as well as those in the literature have been combined in an extensive set of tables providing an up-to-date compilation of these efficiencies. These values are independently being used to derive quantitative structure-activity relationships (QSARs) whereby an optimum set of physical parameters for the phototoxicity to a desired target organism may be ascertained.