Published July 14, 2018 | Version v1
Journal article Open

IN SILICO MOLECULAR DOCKING STUDIES ON PHYTOCOMPOUNDS FROM THE PLANT KALANCHOE PINNATA TARGETING THE PI-CLASS GLUTATHIONE-S-TRANSFERASE OF WUCHERERIA BANCROFTI

Authors/Creators

  • 1. Department of Biotechnology, Thanthai Hans Roever College, Perambalur- 621220, Tamil Nadu, India

Description

Mosquitoes are serious threat to public health through which several dangerous diseases are transmitted in both animals and human beings. The mosquito Culex quinquefasciatus is a significant vector of the filarial nematode, Wuchereria bancrofti, and cause Lymphatic filariasis. The residual spray of insecticides in the control of vector borne diseases is limited. Majority of the chemical pesticides are harmful to man and animals, some of which not easily degradable and spreading toxic effects. In recent years interest in plant based products has been revived because of the development resistance, cross-resistance and possible toxicity hazardous associated with synthetic insecticides and the rise of their cost. In the present study molecular docking analysis were performed using secondary metabolites selected from the plant Kalanchoe pinnata against the glutathione-s-transferase protein of Wuchereria bancrofti. Result suggested that among the four bioactive compounds viz., vitamin D, beta-amyrin, alpha-amyrin and stigmasterolbonded with the Pi-class glutathione –S-transferase protein (PDB ID:5D73) producing a good glide score. Whereas the four compounds, the partition coefficient (QPlogPo/w) and water solubility (QPlogS), critical for estimation of absorption and distribution of drugs within the body ranged between 6.941 to 8.968 and -7.261 to -10.376. Cell permeability (QPPCaco2), a key factor governing drug metabolism and its access to biological membranes, ranged from 3413 to 4557, QPPMDCK ranges from 1864 to 2548M. Overall, the percentage human oral absorption for the compounds ranged 100%. All these pharmacokinetic parameters are within the acceptable range defined for human use, thereby indicating their potential as drug-like molecules

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References

  • Arensburger, P., Megy, K., Waterhouse, R.M., Abrudan, J., Amedeo, P. and Antelo, B. et al., 2010. Sequencing of Culex quinquefasciatus establishes a platform for mosquito comparative genomics. Science, 330, 86-88.
  • Durrheim, D.N., Wynd, S., Liese, B and Gyapong, J.O., 2004. Editorial: Lymphatic filariasis endemicity-an indicator of poverty? Trop. Med. Int. Health, 9, 843-845.
  • Gaddaguti, V., Jwala Mounika, S., Sowjanya, K., Rao, T., Krishna Chakravarthy, M.S.R. and Rao, R.A.P., 2012. GC MS analysis and in silico molecular docking studies of mosquito repellent compounds from Hyptis suaveolens. Int. J. Bioassays., 01(09), 36-41.
  • Indian Council of Medical Research, 2002. Prospects of elimination of lymphatic filariasis in India, Bulletin 32, 5-6.
  • Islam, M.D.S., Patwary, N.I.A., Muzahid, N.H., Shah Md. Shahik, S.Md., Sohel, Md. A. and Hasan, Md. A., 2014. A Systematic Study on Structure and Function of ATPase of Wuchereria bancrofti.Toxicol. Int., 21(3), 269-274.
  • Kitchen, D. B., Decornez, H., Furr, J.R. and Bajorath, J., 2004. Docking and scoring in virtual Screening for drug discovery: Methods and applications. Nat. Rev. Drug Discov., 3(3), 935- 949.
  • Lipinski, C.A., Lombardo, F., Dominy, B.W. and Feeney, P.J., 1997. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development. Adv. Drug Delivery Rev. 23, 3-26.
  • Loganathan, K., Ali, K.S., Rakesh, J.G., Mohan, A., Thulasibabu, R., Gad, R.G., Purushothaman, M., Silambarasan, S., and Nasser, A.J.A., 2015. Small molecule antagonist for EGFR-a preliminary computational framework of azo derivatives as therapeutic agent for bladder cancer. World J. Pharm. Res., 4(8), 1069-1078.
  • Michae, l.E. and Bundy, D.A.P., 1997. Global mapping of lymphatic filariasis, Parasitol. Today, 13, 472-476.
  • Molyneux, D.H. and Zagaria, N., 2002. Lymphatic filariasis elimination: progress in global programme development. Ann. Trop. Med. Parasitol., 96(2), 15-40
  • Nuez, A.D.L, and Rodriguez, R., 2008. Current methodology for the assessment of ADME-Tox properties on drug candidate molecules. Biotec. Apl., 25, 97-110.
  • Ottesen, E.A., 2000. The global programme to eliminatelymphatic filariasis. Trop. Med. Int. Health, 5, 591-594.
  • Ottesen, E.A., Hooper, P.J., Bradley, M. and Biswas, G., 2008. The global programme to eliminate lymphatic filariasis: Health impact after 8 years. PLoS. Negl. Trop. Dis., 2(10), 317.
  • Prueksaritanont, T., and Tang, C., 2012. ADME of Biologics. What Have We Learned from Small Molecules? AAPS J., 14(3), 410-419.
  • Qikprop,2013. Version 3.7. Schrodinger, LLC, New York.
  • Rackham, M.D., Brannigan, J.A., Moss, D.K., Yu, Z., Wilkinson, A.J., Holder, A.A., Tate, E.W and Leather barrow, R.J., 2012. Discovery of Novel and Ligand-Efficient Inhibitors of Plasmodium falciparum falciparum and Plasmodium vivax N-Myristoyl transferase. J. Med. Chem., 56(1), 371-375.
  • Reddy, M.R. and Erion, M.D., 1998. Structure-based drug design approaches for predicting binding affinities of HIV1 protease inhibitors. J. Enzyme Inhib, 14, 1-14.
  • Rocha, A., Broga, C., Belein, M., Carrera, A., Aguiar-santos, A., Oliveira, P., Texeira, M.J., and Funtado, A., 2009. Comparison of tests for the detection of circulating filarial antigen (Og4c3-ELISA and AD 12-ICT) and ultrasound with microfilariae. Men. Inst. Oswaldo Cruz, 104(4), 621-625.
  • Sasa, M., 1976. The antifilariasis campaign. Its History and future prosoects. In: M. Sasa, Human filariasis, A global survey of epidemiology and control, university of Tokyo press, Tokyo, p. 336.
  • Sasidharan, S.Y., Chen, D., Saravanan, K.M., Sundram, L. and Latha, Y., 2011. Extraction, isolation and characterization of bioactive compounds from plants' extracts. Afr. J. Tradit., Compl. Altern. Med., 8(1), 1-10.
  • Schrodinger, L.L.C.,2014.Small-Molecule Drug Discovery Suite 2013-2: Glide, version 6.0, New York.
  • Taylor, R.D., Jewsbury, P.J. and Essex, J.W., 2002. A review of protein-small molecule docking methods. J. Comput. Aided Mol. Des., 16, 151-166.
  • Waterbeemd, H.D. and Gifford, E., 2003. Admet in silico modelling: towards prediction paradise? Nat. Publ. Group, 192-204.
  • World Health Organisation, 2011. Lymphatic filariasis Fact sheet.

Subjects

Zoology
10.5281/zenodo.1312119