Anti-nematodal activity

Antimalarial activity. The dried leaf was inactive on Plasmodium falciparum D-6 and W-2, ICjf, greater than 1000 nmols " h Antimycobacterial activity. Essential oil, on agar plate, was active on AntimycO bacterium smegmatis, MIC 0.1 mg/mL 5 Anti-nematodal activity. Water extract of the dried leaf at variable concentrations produced strong activity on Meloidogyne incognita. ... 

Antimycobacterial activity. Ethanol (95%) and water extracts of the entire plant, on agar plate, were inactive on Mycobacterium tuberculosis ° Leaf juice, on agar plate, produced weak activity on Mycobacterium tuberculosis, MIC less than 1 20 L Anti-nematodal activity. Methanol ex-tract of the fruit, at a concentration of 1 mg/ mL, was active, and the water extract, at a concentration of 10 mg/mL, produced weak activity on Toxacara canis . 

Antileukemic activity. Aucubin, in combination with caffeic acid, chlorogenic acid, ferulic acid, p-coumaric acid, and vanillic acid, exhibited weak antileukemic activity (inhibitory concentration [ICJjo 26-56 pg/ mL, international system of units 2-11) on human leukemia and lymphoma cell lines. Water-insoluble compounds, such as triterpenoids (oleanolic acid and ursolic acid), monotepene (linalool), and flavonoid (luteolin) produced strong activity " . Anti-nematodal activity. Water extract of the dried seed, at various concentrations, was active on Meloidogyne incognita Anti-yeast activity. Ethanol (80%) extract of the dried entire plant, on agar plate at a concentration of 1 mg/mL, was inactive on Candida albicans K... 

A. Structure-Effect Relations between Calystegines and Glycosidases Mechanism of Inhibition Toxicology of Calystegines Possible Medicinal Applications Activity of Calystegines in Plants A. Plant Rhizosphere Allelopathic Activity Insect Feeding Repellent Activity Anti-Nematode Activity Plant-Fungi Interactions... 

The end of patent cover for most of the modern anthelmintics means that market prices have fallen and therefore funds are lower for investment in research into animal health by pharmaceutical companies. As it is the animal health market that drives any search for anti-parasitic drugs by the pharmaceutical companies, few companies are now looking for modern anti-nematodal drugs and the market size for drugs that kill trematodes and cestodes are such that a search for new drugs cannot be financially justified. Unless a novel anthelmintic that kills nematodes happens to have activity against trematodes or cestodes, it is unlikely that new drugs will become available... 

Other benzimidazoles 46 (CDRI 82-437) has been found to display potent anti-filarial activity as it kills almost 100% of the microfilariae and adult worms of L. carinii, D. viteae and Brugia nialayi in rodents both by oral and parenteral route of administrations. The therapeutic dose of this compound is 10-50 mg/kg (i.p. or s.c.) or 100-200 mg/kg (oral) for 5 days. It also shows high activity against hookworms, A. ceylanicum in hamsters at an oral dose of 50 mg/kg [58,59]. Compound 52 (CDRI 81-470) exhibits 100% activity against different nematodes and cestodes in experimental and domestic animals at an oral dose of 2.5-100 mg/kg [67]. The efficacy of... 

Brefeldin (96), an octaketide macrolide with antiviral, cytotoxic, can-cerostatic and phytotoxic activity, was active (50 jig/ml) towards Anguil-lula aceti [142, 157]. Radicicol (monorden) (97), a macrolide antibiotic produced by Deuteromycetes, possesses cytotoxic, antiprotozoal and anti-neoplastic activity [158]. The diethyl ether derivative showed weak activity (LD50 0.2 mg/ml) against a soil nematode, but the cytotoxicity was considerably higher (LD50 3.1 ig/ml) [159]. 

ES-62 is a large and hence immunogenic molecule whose posttranslational addition of PC is dependent on a nematode-spedfic pathway. For these reasons, it is not suitable for use as drug. However, small PC-based derivatives oflFer a viable alternative. Towards this end we have shown that small PC-containii molecules (e.g., PC- cans) can mimic some of the activities of ES-62 in vitro. The next step will be to demonstrate that the same is true with respect to ES-62 s anti-inflammatory activity in vivo. 

Little is known about the nervous systems of cestodes and trematodes except that they probably differ from those of nematodes, since milbemycins and avermectins have no effect on them. However, a highly effective anti schistosomal and antitapeworm agent, praziquantel (see Chapter 54 Clinical Pharmacology of the Anthelmintic Drugs), is known to enhance Ca2+ influx and induce muscular contraction in those parasites, though it exerts no action on nematodes or insects. Some benzodiazepine derivatives have activities similar to those of praziquantel these activities are unrelated to the anxiolytic activities in the mammalian central nervous system. The nerves and muscles in schistosomes and tapeworms are thus interesting subjects for future chemotherapeutic studies. 

Maduramicin (92), a polyether ionophore, has been found as a metabolite of Noccirdia and Actinomadura species [149]. Its structure was determined by X-ray crystallographic studies and an investigation of its biosynthesis revealed that it incorporated 8 acetate, 7 propionate units with 4 methoxy methyls derived from methionine. It displayed anti-malarial [150] and nematocidal activity (0.5-30 ppm) towards phyto- and animal-parasitic nematodes [151]. 

As seen in the sections above, several of the diarylheptanoids of Types I, n, and V have been reported to exhibit various types of biological activities. Most of these studies have been performed on biomedically relevant targets in vitro (e.g. protein kinase C [14], LPS-activated macrophages [22], CC14-challenged hepatocytes [10], but in vivo anti-inflammatory effects have also been demonstrated for some compounds [3, 17]. Toxic effects on parasites, such as nematodes [6,27] and trypanosomatids [8] have also been recorded for the first time. 

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