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Virtual screening and in vitro assay of potential drug like inhibitors from spices against glutathione-S-transferase of filarial nematodes

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Abstract

Glutathione-S-transferase(s) (GST) enzyme from Brugia malayi has been exploited as a target in lymphatic filariasis therapeutics. An active GST is a homodimer of a 208 residue long monomer consisting of two domains, a smaller α/β domain and a larger α domain. The components of the glutathione (GSH) system, mainly GST enzymes, are critical antioxidant and detoxification system responsible for the long-term existence of filarial worms in mammalian host; hence they are major chemotherapeutic targets in filarial species. In the present study, 58 phytochemicals from 10 plants, predicted and reported to have potential nematicidal activity and ADMET satisfaction, have been docked to GST enzyme of B. malayi to assess their binding affinity and consequently their inhibitory activity. A comparative study has been made with commonly employed chemotherapeutic GST inhibitors such as cibacron-blue, butylated hydroxyanisole, hexyl glutathione and ethacrynic acid. In vitro effects of potential drug like compound from in silico results have been done for validation of docking studies. In vitro assay revealed efficacy in GST inhibition in the following compounds: linalool (97.50%), alpha-pinene (90.00%), strychnine (87.49%), vanillin (84.99%), piperine (79.99%), isoeugenol (62.49%), curcumin (57.49%), beta-caryophyllene (39.50%), cinnamic acid (27.49%), capsaicin (19.99%), citronellol (19.99%) and geraniol (17.49%). An online database (www.spicebioinfo.res.in/gstleadbase) has been developed, which will serve as a useful repository of information on GST inhibitors for future development of drugs against filarial nematodes. These findings thus suggest that the above phytochemicals could be potentially developed as lead molecules for targeting GST of lymphatic filarial parasites.

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Acknowledgments

We acknowledge with thanks the facilities provided by Director, Indian Institute of Spices Research (IISR), Calicut; Dr. Santhosh J. Eapen, Co-ordinator, Distributed Information Sub-Centre (DBT, New Delhi), of IISR (Indian Institute of Spices Research), Dr. O.K. Sindu, District Veterinary Centre Campus, Calicut, who supplied the filarial nematodes Dirofilaria immitis and the assistance rendered by Ms. M. Dinsha, Senior Research Fellow, IISR.

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  1. Indian Institute of Spices Research, Calicut, 673012, Kerala, India

    Shamina Azeez, Rosana O. Babu, Riju Aykkal & Reena Narayanan

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  1. Shamina Azeez
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  2. Rosana O. Babu
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  3. Riju Aykkal
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  4. Reena Narayanan
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Correspondence to Shamina Azeez.

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Azeez, S., Babu, R.O., Aykkal, R. et al. Virtual screening and in vitro assay of potential drug like inhibitors from spices against glutathione-S-transferase of filarial nematodes. J Mol Model 18, 151–163 (2012). https://doi.org/10.1007/s00894-011-1035-2

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  • DOI: https://doi.org/10.1007/s00894-011-1035-2

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