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Tautomeric origin of dual effects of N1-nicotinoyl-3-(4′-hydroxy-3′-methyl phenyl)-5-[(sub)phenyl]-2-pyrazolines on bacterial and viral strains: POM analyses as new efficient bioinformatics’ platform to predict and optimize bioactivity of drugs

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Abstract

In this study, we have amalgamated computational methodologies, viz. Petra, Osiris and Molinspiration (POM) to identify pharmacophores and antipharmacophores for antibacterial/antiviral activities of some 2-pyrazolines derivatives. Lipophilicity and the presence of tautomerism process are the major factors that govern the orientation to antibacterial and/or antiviral activity. On other hand, it was observed that these compounds have two different active sites and can inhibit both antiviral and antibacterial strains. Further, we have carried out receptor-based electrostatic analysis to confirm the electronic, steric and hydrophobic requirements for future modifications. The analyses provide substantial idea about the structural features responsible for their combined antibacterial/antiviral activity and provide guidelines for further modifications, with the aim of improving the activity and selectivity of designed drugs targeting HIV and tuberculosis microorganisms.

Graphical Abstract

The speculative assertions presented in many papers published in many reputed journals are meaningless. Most of the authors discuss of the antiviral activity compared to the antibacterial activity. There authors seem to consider that there is only one tautomeric form taking one mechanism of action for both antiviral and antibacterial activities. This is false; here, we clarify things on the basis of POM analyses.

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Acknowledgments

Prof. T. Ben Hadda would like to thank the ACTELION; the Biopharmaceutical Company of Swiss, for the on-line molecular properties calculations and to Ministry of High Science and Education of Rabat (Morocco) for financial support.

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Authors and Affiliations

  1. Laboratoire Chimie Matériaux, Faculté des Sciences, Mohammed First University, 60000, Oujda, Morocco

    Taibi Ben Hadda

  2. New Drug Discovery Research, Department of Medicinal Chemistry, Sunrise University, Alwar, 301030, Rajasthan, India

    Mohamed A. Ali

  3. Department of Chemistry, Vidya Bharati College, Amravati, 444602, Maharashtra, India

    Vijay Masand

  4. Laboratoire Chimie Plantes Synthèse Organique et Bioorganique, Faculté des Sciences, Université Mohammed V-Agdal, Rabat, Morocco

    Said Gharby

  5. Laboratoire de Chimie Physique des Biomolécules et Interfaces Biologiques, Faculté des Sciences de la Nature et de la Vie, Université de Mascara, 29000, Mascara, Algeria

    Teffaha Fergoug

  6. Department of Chemistry, King Saud University, Riyadh, 11451, Saudi Arabia

    Ismail Warad

  7. Institute for Research in Molecular Medicine, Universiti Sains Malaysia, 11800, Minden, Penang, Malaysia

    Mohamed A. Ali

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  1. Taibi Ben Hadda
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Correspondence to Taibi Ben Hadda.

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Hadda, T.B., Ali, M.A., Masand, V. et al. Tautomeric origin of dual effects of N1-nicotinoyl-3-(4′-hydroxy-3′-methyl phenyl)-5-[(sub)phenyl]-2-pyrazolines on bacterial and viral strains: POM analyses as new efficient bioinformatics’ platform to predict and optimize bioactivity of drugs. Med Chem Res 22, 1438–1449 (2013). https://doi.org/10.1007/s00044-012-0143-6

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