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QSAR modeling for the prediction of pGI50 activity of compounds on LOX IMVI cell line and ligand-based design of potent compounds using in silico virtual screening

  • Bello Abdullahi UmarEmail author
  • Adamu Uzairu
  • Gideon Adamu Shallangwa
  • Uba Sani
Original Article
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Abstract

The anti-melanoma activity (pGI50) values of 71 compounds from the National Cancer Institute (NCI) data bank on LOX IMVI cell line were modeled to illustrate the Quantitative structure–activity relationship (QSAR) of the compounds. The genetic function algorithm (GFA) has been used to select the most relevant descriptors so as to improve the performance of the QSAR model. The statistical significance of the model was verified based on the values of validation parameters such as \( R_{{{\text{train}} }}^{2} \) (0.867), \( R_{{{\text{adj}} }}^{2} \) (0.848), \( Q_{{{\text{cv}} }}^{2} \) (0.809) and \( R_{{{\text{test}} }}^{2} \) (0.749) needed to evaluate the robustness and strength of the model. The result of the internal and external validation of the model indicates that the model is good and could be used to predict pGI50 of anti-melanoma compounds on LOX IMVI cell line for which no experimental data are available. Compound 41 was selected using in-silico screening method as a template due to its good pGI50 (9.793) and was utilized to design new potent compounds, thereby enhancing the activity of the parent structure. Ten (10) new potent compounds were deigned and predicted using the proposed model. The predicted pGI50 of the majority of the designed analogous were more than the lead compound 41 used for the design and among which compound N5 showed the best activity (pGI50=13.186). Thus, this study provides a valuable approach and new direction to novel drug discovery.

Keywords

LOX IMVI cell line NCI Anti-melanoma GFA-MLR QSAR Williams plot 

Notes

Acknowledgements

The authors sincerely acknowledge Ahmadu Bello University, Zaria for providing the softwares used and all the members of the group for their advice and encouragement in the cause of this research.

Funding

The authors received no direct funding for this research.

Compliance with ethical standards

Conflict of interest

The authors have declared they have no conflict of interest.

Human and animal rights statement

This article does not contain any studies with human or animal subjects.

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Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2019

Authors and Affiliations

  • Bello Abdullahi Umar
    • 1
    Email author
  • Adamu Uzairu
    • 1
  • Gideon Adamu Shallangwa
    • 1
  • Uba Sani
    • 1
  1. 1.Department of Chemistry, Faculty of Physical SciencesAhmad Bello UniversityZariaNigeria

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