Antifilarial actions of green tea extract and a synthetic heterocyclic thiazolidine derivative, Im8 compound in experimental mouse model.

In spite of the advances in drug development and research against human lymphatic filariasis following the WHO mandate to address the disease-associated socioeconomic burden, diethylcarbamazine (DEC, N, N-diethyl-4-methyl-1-piperazine carboxamide) is the only available antifilarial drug to date. The major obstacle for further development of antifilarial drugs is the lack of validation of candidate drugs in the experimental animal models. Both, green tea extract and a synthetic heterocyclic thiazolidine derivative (Im8; 2-chloro-N-(4-phenylthiazol-2-yl), showed efficacy of antifilarial action in our earlier in vitro study and hence, they were screened in the present study for their antifilarial potential in the BALB/c mouse filariasis model. Mice were treated with 25 mg/kg dose of either Im8 or green tea extract or DEC or only with their respective vehicles. The untreated mice served as controls. Following insertion of the micropore chamber laden with microfilariae (Mf) of Brugia malayi, the drug or vehicle was administered s.c. in mice at 12 h intervals as 4 doses. After 12 h of administration of the last dose, the micropore chambers were removed to determine the action of the treatments as the loss of Mf motility. The green tea extract showed a significant antifilarial action and Im8 showed relatively less but significant antifilarial action as compared to the respective vehicle controls. Both the green tea extract and Im8 showed higher activity than that was exerted by DEC. These results revealed a greater efficacy of green tea and thiazolidine derivative, Im8 as the novelantifilarial agents in the experimental mouse model of filariasis.

Targeting folate metabolism for therapeutic option: A bioinformatics approach.

Lymphatic filariasis, commonly called elephantiasis, poses a burden of estimated level of 5.09 million disability adjusted life year. Limitations of its sole drug, diethylcarbamazine (DEC) drive exploration of effective filarial target. A few plant extracts having polyphenolic ingredients and some synthetic compounds possess potential dihydrofolate reductase (DHFR) inhibitory effect. Here, we postulated a plausible link between folates and polyphenolics based on their common precursor in shikimate metabolism. Considering its implication in structural resemblance based antagonism, we have attempted to validate parasitic DHFR protein as a target. The bioinformatics approach, in the absence of crystal structure of the proposed target, used to authenticate and for virtual docking with suitable tested compounds, showed remarkably lower thermodynamic parameters as opposed to the positive control. A comparative docking analysis between human and Brugia malayi DHFR also showed effective binding parameters with lower inhibition constants of these ligands with parasitic target, but not with human counterpart highlighting safety and efficacy. This study suggests that DHFR could be a valid drug target for lymphatic filariasis, and further reveal that bioinformatics may be an effective tool in reverse pharmacological approach for drug design.