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Urgent need to develop newer drugs to kill adult filarial worms in lymphatic system: Dr. Nisha Mathew

Peethaambaran Kunnathoor, Chennai
Tuesday, November 14, 2017, 08:00 Hrs  [IST]

There is an urgent need to develop an effective drug to kill or permanently sterilize the adult worms in the lymphatic system because no drug has proved yet as a magic bullet against adult filarial worms.
Though there is add-ons to the existing knowledge on newer molecules with antifilarial activity, no drug has come out as a remedy with highly specific properties to eliminate the worms, according to Dr. Nisha Mathew, professor at the ICMR-Vector Control Research Centre in Pondicherry.
The drugs currently used for Lymphatic Filariasis include Diethylcarbamazine (DEC) and Ivermectin, either alone or in combination with albendazole. But, none of these is effective in killing the long lived adult worms, she said while speaking in a seminar on ‘mosquito-borne diseases‘.
Lymphatic Filariasis is one of the neglected tropical diseases (NTDs) among the 20 NTDs listed by the World Health Organisation (WHO). It is caused by the infection with parasitic filarial nematodes, Wuchereria bancrofti, Brugia malayi and B. Timori, which are transmitted through mosquito bites.
Target structure based drug design is one of the several approaches for developing anti-parasitic agents and this method has gained importance in recent years. Few targets for chemotherapy have been identified in filariae and other parasitic nematodes. Filarial glutathione S transferase (GST) has been identified as a potential biochemical target for antifilarial drug development.
Similarly, ligand design, receptor-ligand docking, synthesis and screening of compounds for selective toxicity to filarial GST and in vitro evaluation of effective GST inhibitors for macrofilaricidal activity have been carried out.
Molecular docking was carried out with the comparatively modeled 3D-structure of wbGST as the receptor and the substituted naphthoquinones (NPQs) as ligands. Substituted amino NPQs were synthesized by direct amination. All the molecules were screened for antifilarial activity against filarial GST as drug target followed by in vitro evaluation by worm motility and MTT reduction assay.
The results of in silico and in vitro studies with the synthesized 1, 4 - naphthoquinone analogues on filarial GST and in vitro  macrofilaricidal activity has open up a promising biochemical target for antifilarial drug development, said Dr. Nisha.


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