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Molecular drug design, synthesis and pharmacophore site identification of spiroheterocyclic compounds: Trypanosoma crusi inhibiting studies

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Abstract

Synthesis and evaluation of the bioactivity of spiroheterocycles (STC) against Trypanosoma cruzi are described. Selectivity indices were improved for two compounds versus the leads 17 and 20, the spiro-thiochromanone (STC) derivatives 17–26, thus increasing the therapeutic interest of our family. As our previous studies conducted on the structure of pharmacophore sites of our compounds made us hypothesize the existence of original sites, STC can be considered as promising tools further anti-trypanosoma studies, as probes for affinity chemotherapy. Compounds 17 and 20 are more potent and more selective than benznidazole and nifurtimox.

Graphical abstract

The highest anti-trypanosoma cruzi (TC) activity is obtained for compounds 17 and 20 which exhibited low IC50 values (1.5 and 3.78 μM), up to sixfold lower than clinical drugs, nifurtimox (Nfx) or up to fourfold lower than benznidazole (Bdz).

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Acknowledgments

We are grateful to staff of Federal University of Pernambuco, Recife-Brazil for the help in biological assay. Prof. T. Ben Hadda would like to thank the ACTELION; the Biopharmaceutical Company of Swiss, for the online molecular properties calculations.

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Authors and Affiliations

  1. Laboratoire Chimie Matériaux, Faculté Sciences, Université Mohamed I, Oujda, Morocco

    Taibi Ben Hadda

  2. Laboratoire Chimie Organique, Université Sidi Mohamed Ben Abdellah, Fès, Morocco

    Abdelali Kerbal, Brahim Bennani, Ghali Al Houari & Maria Daoudi

  3. LabSINFA, DPS-CHS, Federal University of Pernambuco, Recife, Brazil

    Ana C. L. Leite

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

    Vijay H. Masand

  5. Department of Pharmaceutical Chemistry, Sahyadri College of Pharmacy, Methawade, Sangola, Solapur, 413307, Maharashtra, India

    Rahul D. Jawarkar

  6. Laboratoire Chimie Plantes Synthèse Organique Et Bioorganique, FS, Rabat, Morocco

    Zoubida Charrouf

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  1. Taibi Ben Hadda
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  2. Abdelali Kerbal
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  8. Rahul D. Jawarkar
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  9. Zoubida Charrouf
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Correspondence to Taibi Ben Hadda or Rahul D. Jawarkar.

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Ben Hadda, T., Kerbal, A., Bennani, B. et al. Molecular drug design, synthesis and pharmacophore site identification of spiroheterocyclic compounds: Trypanosoma crusi inhibiting studies. Med Chem Res 22, 57–69 (2013). https://doi.org/10.1007/s00044-012-0010-5

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  • DOI: https://doi.org/10.1007/s00044-012-0010-5

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