Inhibition of Wb-iPGM using analogues of Clorsulon and co-administration with DEC for bancroftian filariasis treatment

Wucherria bancroft i (Wb) is the main causative agent of Filariasis. Lym- phatic Filariasis (LF) is a disabling, disfiguring, and a poverty promoting disease which is caused by the parasitic filarial nematode worms. The identification of essen- tial nematode genes has shown that independent phosphoglycerate mutase (iPGM) is an excellent drug target against parasitic nematodes. In this current study, we have used our previously modeled structure of Wb-iPGM to inhibit the Embden Mayerhoff pathways of Wb using the Clorsulon and their analogues. Further, these analogues were scrutinized based on the pharmacokinetics and best complex were proposed to inhibit the Wb-iPGM enzyme. This current study provides an insight towards the pro- cess of design and development of novel drug target and their mode of interaction with the potent anthelmintic drugs.

[1]  J C Madden,et al.  Classification of chemicals according to mechanism of aquatic toxicity: an evaluation of the implementation of the Verhaar scheme in Toxtree. , 2008, Chemosphere.

[2]  R. Martin,et al.  Modes of action of anthelmintic drugs. , 1997, Veterinary journal.

[3]  Zakia Bibi,et al.  Nutrition & Metabolism BioMed Central Review Role of cytochrome P450 in drug interactions , 2008 .

[4]  Michael P Barrett,et al.  Energy generation in insect stages of Trypanosoma brucei: metabolism in flux. , 2005, Trends in parasitology.

[5]  Muthuvel Suresh Kumar,et al.  Drug targets for lymphatic filariasis: a bioinformatics approach. , 2013, Journal of vector borne diseases.

[6]  Richard A. Friesner,et al.  Flexible ligand docking with Glide. , 2007, Current protocols in bioinformatics.

[7]  J. Foster,et al.  Mining Predicted Essential Genes of Brugia malayi for Nematode Drug Targets , 2007, PloS one.

[8]  J. Foster,et al.  Cofactor-independent Phosphoglycerate Mutase Has an Essential Role in Caenorhabditis elegans and Is Conserved in Parasitic Nematodes* , 2004, Journal of Biological Chemistry.

[9]  M. J. Jedrzejas,et al.  Mechanism of Catalysis of the Cofactor-independent Phosphoglycerate Mutase from Bacillus stearothermophilus , 2000, The Journal of Biological Chemistry.

[10]  Francis H. Zenie,et al.  Accelerating Drug Discovery , 1994, Bio/Technology.

[11]  P. Das,et al.  An allele specific PCR assay for screening for drug resistance among Wuchereria bancrofti populations in India. , 2009, The Indian journal of medical research.

[12]  Syed P Hasan,et al.  Noncompliance leading to drug accumulation resulting in phenytoin toxicity. , 2003, Journal of the National Medical Association.

[13]  P. Galtier,et al.  Fasciola hepatica: influence of gender and liver biotransformations on flukicide treatment efficacy of rats infested and cured with either clorsulon/ivermectin or triclabendazole. , 2000, Experimental parasitology.

[14]  M. Bhat,et al.  Hyperglycemia regulates MDR‐1, drug accumulation and ROS levels causing increased toxicity of carboplatin and 5‐fluorouracil in MCF‐7 cells , 2011, Journal of cellular biochemistry.

[15]  Modeling, docking, simulation, and inhibitory activity of the benzimidazole analogue against β-tubulin protein from Brugia malayi for treating lymphatic filariasis , 2012, Medicinal Chemistry Research.

[16]  R. K. Shenoy,et al.  Treatment of lymphatic filariasis: current trends. , 2001, Indian journal of dermatology, venereology and leprology.

[17]  B. Strodel,et al.  Molecular modeling, dynamics, and an insight into the structural inhibition of cofactor independent phosphoglycerate mutase isoform 1 from Wuchereria bancrofti using cheminformatics and mutational studies , 2013, Journal of biomolecular structure & dynamics.

[18]  P. J. Hooper,et al.  The Global Programme to Eliminate Lymphatic Filariasis: Health Impact after 8 Years , 2008, PLoS neglected tropical diseases.

[19]  N. Arunachalam,et al.  Effectiveness of two annual, single‐dose mass drug administrations of diethylcarbamazine alone or in combination with albendazole on soil‐transmitted helminthiasis in filariasis elimination programme , 2004, Tropical medicine & international health : TM & IH.

[20]  H. van de Waterbeemd,et al.  ADMET in silico modelling: towards prediction paradise? , 2003, Nature reviews. Drug discovery.

[21]  F. Lombardo,et al.  Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. , 2001, Advanced drug delivery reviews.

[22]  Joëlle Quetin-Leclercq,et al.  NL MIND-BEST: a web server for ligands and proteins discovery--theoretic-experimental study of proteins of Giardia lamblia and new compounds active against Plasmodium falciparum. , 2011, Journal of theoretical biology.

[23]  A. R. Rivas-Alcalá,et al.  CHEMOTHERAPY OF ONCHOCERCIASIS: A CONTROLLED COMPARISON OF MEBENDAZOLE, LEVAMISOLE, AND DIETHYLCARBAMAZINE , 1981, The Lancet.

[24]  B. Duke.  Lymphatic and other filariases. , 1981, British medical journal.

[25]  R. Wade,et al.  The role of hydrogen-bonds in drug binding. , 1989, Progress in clinical and biological research.

[26]  J Devillers,et al.  Evaluation of the OECD QSAR Application Toolbox and Toxtree for estimating the mutagenicity of chemicals. Part 2. α-β unsaturated aliphatic aldehydes , 2010, SAR and QSAR in environmental research.

[27]  A. Y. Lu,et al.  Role of pharmacokinetics and metabolism in drug discovery and development. , 1997, Pharmacological reviews.

[28]  C. Lipinski.  Drug-like properties and the causes of poor solubility and poor permeability. , 2000, Journal of pharmacological and toxicological methods.

[29]  P. Skuce,et al.  Benzimidazole resistance allele haplotype diversity in United Kingdom isolates of Teladorsagia circumcincta supports a hypothesis of multiple origins of resistance by recurrent mutation. , 2010, International journal for parasitology.