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Probing the opportunities for designing anthelmintic leads by sub-structural topology-based QSAR modelling

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Abstract

A quantitative structure–activity (QSAR) model has been developed for enriched tubulin inhibitors, which were retrieved from sequence similarity searches and applicability domain analysis. Using partial least square (PLS) method and leave-one-out (LOO) validation approach, the model was generated with the correlation statistics of \(q^{2}\) and \(r_\mathrm{pred}^2 \) of 0.68 and 0.69, respectively. The present study indicates that topological descriptors, viz. BIC, CH_3_C, IC, JX and Kappa_2 correlate well with biological activity. ADME and toxicity (or ADME/T) assessment showed that out of 260 molecules, 255 molecules successfully passed the ADME/T assessment test, wherein the drug-likeness attributes were exhibited. These results showed that topological indices and the colchicine binding domain directly influence the aetiology of helminthic infections. Further, we anticipate that our model can be applied for guiding and designing potential anthelmintic inhibitors.

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Abbreviations

MAE:

Mean analysis error

PSA:

Polar surface area

BBB:

Blood brain barrier

WHO:

World Health Organization

LDA:

Linear discriminant analysis

MLR:

Multi linear regression

ANN:

Artificial neural network

OECD:

Organization for Economic Co-operation and Development

NTDs:

Neglected tropical diseases

STH:

Soil transmitted helminths

nNE:

Number of negative prediction error value

nPE:

Number of positive prediction error value

FCFP:

Functional class fingerprints

DS:

Discovery Studio

SmTGR:

Schistosoma mansoni thioredoxin-glutathione reductase

S-PLS:

Stepwise-partial least square

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Acknowledgements

Prabodh Ranjan would like to thank the financial support from the University Grants Commission (UGC), Govt. of India. Mohd Athar acknowledges generous support from the Department of Science and Technology (DST), Govt. of India as INSPIRE-SRF Fellowship. Prakash C. Jha also would like to thank UGC for providing SERB (EMR/2016/003025) Grant, and the Central University of Gujarat for providing basic computational facilities. Discussion with Dr. Pravin Ambure, University of Gdansk, Poland are also gratefully acknowledged.

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  1. CCG@CUG, School of Chemical Sciences, Central University of Gujarat, Sector-30, Gandhinagar, Gujarat, 382030, India

    Prabodh Ranjan & Mohd Athar

  2. CCG@CUG, Centre for Applied Chemistry, Central University of Gujarat, Sector-30, Gandhinagar, Gujarat, 382030, India

    Prakash Chandra Jha

  3. Department of Chemistry, School of Advanced Sciences, VIT University, Vellore, Tamil Nadu, 632014, India

    Kari Vijaya Krishna

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  1. Prabodh Ranjan
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Correspondence to Prakash Chandra Jha.

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Ranjan, P., Athar, M., Jha, P.C. et al. Probing the opportunities for designing anthelmintic leads by sub-structural topology-based QSAR modelling. Mol Divers 22, 669–683 (2018). https://doi.org/10.1007/s11030-018-9825-4

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