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

Molecular diversity 2022 Aug

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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 Eleven adducts (8 of them unpublished) with yields between 58 and 80% were obtained from this reaction, which were adequately characterized.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. Molecular hybridization technique combined with the Morita-Baylis-Hillman reaction provided new thymol derivatives with giardicidal activity superior to the precursor molecules. © 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.

Citation

Francisco J S Xavier, Andressa B Lira, Gabriel C Verissimo, Fernanda S de S Saraiva, Abrahão A de Oliveira Filho, Elaine M de Souza-Fagundes, Margareth de F F M Diniz, Maria A Gomes, Aleff C Castro, Fábio P L Silva, Claudio G Lima-Junior, Mário L A A Vasconcellos. Morita-Baylis-Hillman adducts derived from thymol: synthesis, in silico studies and biological activity against Giardia lamblia. Molecular diversity. 2022 Aug;26(4):1969-1982