"Novel chemo-enzymatic synthesis, structural elucidation and first antiprotozoal activity profiling of the atropoisomeric dimers of trans-8-Hydroxycalamenene".

Autor: Bassanini I; Istituto di Scienze e Tecnologie Chimiche ''Giulio Natta'' - SCITEC, Consiglio Nazionale delle Ricerche, Via Mario Bianco 9, 20131 Milano, Italy. Electronic address: ivan.bassanini@cnr.it., Tognoli C; Istituto di Scienze e Tecnologie Chimiche ''Giulio Natta'' - SCITEC, Consiglio Nazionale delle Ricerche, Via Mario Bianco 9, 20131 Milano, Italy. Electronic address: chiara.tognoli@scitec.cnr.it., Meli M; Istituto di Scienze e Tecnologie Chimiche ''Giulio Natta'' - SCITEC, Consiglio Nazionale delle Ricerche, Via Mario Bianco 9, 20131 Milano, Italy. Electronic address: massimiliano.meli@scitec.cnr.it., Parapini S; Dipartimento di Scienze Biomediche per la Salute, Università degli Studi di Milano, Via Pascal 36, 20133, Milano, Italy. Electronic address: silvia.parapini@unimi.it., Basilico N; Dipartimento di Scienze Biomediche, Chirurgiche ed Odontoiatriche, Università degli Studi di Milano, Via Pascal 36, 20133, Milano, Italy. Electronic address: nicoletta.basilico@unimi.it., Fronza G; Istituto di Scienze e Tecnologie Chimiche ''Giulio Natta''- SCITEC, Consiglio Nazionale delle Ricerche, Via Luigi Mancinelli 7, 20131, Milano, Italy. Electronic address: giovanni.fronza@scitec.cnr.it., Serra S; Istituto di Scienze e Tecnologie Chimiche ''Giulio Natta''- SCITEC, Consiglio Nazionale delle Ricerche, Via Luigi Mancinelli 7, 20131, Milano, Italy. Electronic address: stefano.serra@scitec.cnr.it., Riva S; Istituto di Scienze e Tecnologie Chimiche ''Giulio Natta'' - SCITEC, Consiglio Nazionale delle Ricerche, Via Mario Bianco 9, 20131 Milano, Italy. Electronic address: sergio.riva@scitec.cnr.it.
Jazyk: angličtina
Zdroj: Bioorganic chemistry [Bioorg Chem] 2024 Dec; Vol. 153, pp. 107917. Date of Electronic Publication: 2024 Oct 24.
DOI: 10.1016/j.bioorg.2024.107917
Abstrakt: Leishmaniasis and malaria are two debilitating protozoan diseases affecting millions globally, particularly in tropical and subtropical regions. Current therapeutic options face significant challenges due to emerging drug-resistant strains, necessitating the discovery of novel antiprotozoal agents. This study explores, for the first time, the antiprotozoal potential of calamenenes and their dimers, naturally occurring sesquiterpenes found in essential oils, through a novel chemo-enzymatic synthesis approach. Using the laccase from Trametes versicolor, atropoisomeric dimers of (-)- and (+)-8-trans-hydroxycalamenene were synthesized from commercially available (-)- and (+)-menthol. Structural elucidation was achieved via 2D-NMR spectroscopy, electronic circular dichroism, and DFT calculations. In vitro profiling against Leishmania spp and drug-resistant Plasmodium falciparum revealed that calamenene dimers exhibited significantly higher antiprotozoal activity compared to their monomeric counterparts, highlighting the potential of dimeric terpenoids as promising antiprotozoal agents. This work lays the foundation for developing novel antimalarial drugs based on calamenene scaffolds, encouraging further interactome studies to optimize their pharmacological properties.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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