Development of novel anti-filarial agents using carbamo(dithioperoxo)thioate derivatives.

A series of novel carbamo(dithioperoxo)thioate derivatives have been prepared in excellent yield using a significantly fast, one-pot three component reaction and experimented for their potential as anti-filarial agents against model filarial nematode Setaria cervi. Among 23 compounds (4a-w) evaluated for the anti-filarial activities, five compounds (4a, 4b, 4c, 4d and 4h) have shown promising anti-proliferative effects on the juvenile stage microfilariae (mf) as well as in adults in a time and dose dependent manner. Compound 4a was found most active against oocytes, mf and adult nematods as well as non-cytotoxic to the normal cells. It has been established that the anti-filarial activity of the compounds were observed due to the involvement of reactive oxygen species (ROS) and apoptosis. Several biochemical and microscopic experiments have been carried out to establish the fact that both intrinsic and extrinsic pathways of apoptosis contribute to the compound 4a mediated death phenomenon of the filarial nematodes.

Reduction in the number of infective Trichinella spiralis larvae in mice by use of homeopathic drugs.

BACKGROUND: Trichinellosis caused by the gastrointestinal nematode Trichinella spiralis occurs in humans, domestic animals and wild animals. It is difficult to control the muscle phase of the parasite. Homeopathic drugs such as Cina and Santoninum have anthelmintic properties. We have observed that in material doses, the homeopathic drug Podophyllum also has nematotoxic properties. We have also observed that homeopathic potency can influence the water permeability of cells. OBJECTIVE: The purpose of this study was to investigate whether potentized homeopathic drugs such as Cina 30, Santoninum 30 and Podophyllum mother tincture can affect the muscle phase of the parasite T. spiralis in mice. Another objective was to see whether trichinellosis and its treatment with the 3 named homeopathic drugs could alter the water content in the muscle tissue of mice. MATERIALS AND METHODS: Cina 30 and Santoninum 30 were prepared from the mother tincture of the flowering tops of Artemisia nilagirica and its active principle santonin, in each case by successive dilution (1:100) with 90% ethanol and sonication in 30 steps following the single glass method (K30). Ethanol 30 was prepared by successive dilution of 90% ethanol with 90% ethanol (1:100) followed by sonication in 30 steps. In each step, the dilution was sonicated at 20 KHz for 30 s. We have observed before that sonication is a more uniform, measurable and effective process of mechanical agitation of a liquid than manual succussion. Experimentally infected mice were orally treated with an aqueous Podophyllum suspension at 60 mg/kg/day. Each potentized drug was diluted 1:20 with distilled water and administered orally at 0.05 ml/mouse/day. Each mouse was inoculated with T. spiralis larvae at a dose of 200 larvae/mouse by esophageal intubation. Treatment was started on day 7 post-infection and continued for 120 days. After completion of treatment, the mice were sacrificed and the larvae were extracted from muscles by HCl-pepsin digestion. The water content of the muscles was measured by determining the difference between fresh weight and dry weight of the tissue. RESULTS: Podophyllum Theta, Cina 30 and Santoninum 30 reduced the larval population in the studied mice by 68.14%, 84.10% and 81.20%, respectively, as compared to the untreated control group. Ethanol 30 achieved no significant reduction in the larval population compared to the untreated control group. The water content of the muscle tissue in the untreated control group and the Podophyllum-treated groups was significantly higher than in the Ethanol 30-, Cina 30- and Santoninum 30-treated groups. CONCLUSIONS: (1) Podophyllum Theta, Cina 30 and Santoninum 30 were effective in the muscle phase of T. spiralis infection and significantly reduced the larval population in the treated mice. The potencies were more effective than the mother tincture, an effect which was not due to the medium ethanol. (2) The potencies significantly reduced the water content of the muscle tissue which might have affected the larvae. The effect of Podophyllum Theta might be due to the direct toxic effect of the drug on the larvae.