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Morita–Baylis–Hillman adducts derived from thymol: synthesis, in silico studies and biological activity against Giardia lamblia

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Abstract

Giardiasis is a neglected disease, and there is a need for new molecules with less side effects and better activity against resistant strains. This work describes the evaluation of the giardicidal activity of thymol derivatives produced from the Morita–Baylis–Hillman reaction. Thymol acrylate was reacted with different aromatic aldehydes, using 1,4-diazabicyclo[2.2.2]octane (DABCO) as a catalyst. Eleven adducts (8 of them unpublished) with yields between 58 and 80% were obtained from this reaction, which were adequately characterized. The in silico prediction showed theoretical bioavailability after oral administration as well as antiparasitic activity against Giardia lamblia. Compound 4 showed better biological activity against G. lamblia. In addition to presenting antigiardial activity 24 times better than thymol, this MBHA was obtained in a short reaction time (3 h) with a yield (80%) superior to the other investigated molecules. The molecule was more active than the precursors (thymol and MBHA 12) and did not show cytotoxicity against HEK-293 or HT-29 cells. In conclusion, this study presents a new class of drugs with better antigiardial activity in relation to thymol, acting as a basis for the synthesis of new bioactive molecules.

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Molecular hybridization technique combined with the Morita–Baylis–Hillman reaction provided new thymol derivatives with giardicidal activity superior to the precursor molecules.

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Acknowledgements

The authors are grateful for financial support from the Brazilian agencies National Council for Scientific and Technological Development (CNPq), Minas Gerais Research Foundation (FAPEMIG), Coordination for the Improvement of Higher Education Personnel (CAPES), Federal Universities of Paraíba (UFPB) and Minas Gerais (UFMG).

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Authors and Affiliations

  1. Laboratory of Medicinal Organic Synthesis of Paraíba (LASOM-PB), Department of Chemistry, Federal University of Paraíba, João Pessoa, PB, 58.051-900, Brazil

    Francisco J. S. Xavier, Aleff C. Castro, Fábio P. L. Silva, Claudio G. Lima-Junior & Mário L. A. A. Vasconcellos

  2. Postgraduate Program in Natural and Synthetic Bioactive Products, Federal University of Paraíba, João Pessoa, PB, 58.051-900, Brazil

    Andressa B. Lira & Margareth de F. F. M. Diniz

  3. Department of Parasitology, Federal University of Minas Gerais, Belo Horizonte, MG, 31270-901, Brazil

    Gabriel C. Verissimo & Maria A. Gomes

  4. Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, MG, 31270-901, Brazil

    Fernanda S. de S. Saraiva & Elaine M. de Souza-Fagundes

  5. Academic Unit of Biological Sciences, Center for Health and Rural Technology, Federal University of Campina Grande, Patos, PB, 58.708-110, Brazil

    Abrahão A. de Oliveira Filho

  6. Department of Pharmaceutical Sciences, Federal University of Paraíba, João Pessoa, PB, 58.051-900, Brazil

    Margareth de F. F. M. Diniz

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Xavier, F.J.S., Lira, A.B., Verissimo, G.C. et al. Morita–Baylis–Hillman adducts derived from thymol: synthesis, in silico studies and biological activity against Giardia lamblia. Mol Divers 26, 1969–1982 (2022). https://doi.org/10.1007/s11030-021-10308-1

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