New derivatives from dehydrodieugenol B and its methyl ether displayed high anti-Trypanosoma cruzi activity and cause depolarization of the plasma membrane and collapse the mitochondrial membrane potential
In: ISSN: 0009-2797 ; Chemico-Biological Interactions ; https://hal.science/hal-03798572 ; Chemico-Biological Interactions, 2022, 366, pp.110129. ⟨10.1016/j.cbi.2022.110129⟩, 2022
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International audience ; In the present work, dehydrodieugenol B (1) and its methyl ether (2), isolated from Nectandra leucantha twigs, were used as starting material for the preparation of two new derivatives (1a and 2a) containing an additional methoxycarbonyl unit on allyl side chains. Compounds 1a and 2a demonstrated activity against trypomastigotes (EC(50) values of 13.5 and 23.0 μM, respectively) and against intracellular amastigotes (EC(50) values of 10.2 and 6.1 μM, respectively). Additionally, compound 2a demonstrated no mammalian cytotoxicity up to 200 μM whereas compound 1a exhibited a CC(50) value of 139.8 μM. The mechanism of action studies of compounds 1a and 2a demonstrated a significant depolarization of the plasma membrane potential in trypomastigotes, followed by a mitochondrial membrane potential collapse. Neither calcium level nor reactive oxygen species alterations were observed after a short-time incubation. Considering the potential of compound 2a against T. cruzi and its simple preparation from the natural product 2, isolated from N. leucantha, this compound could be considered a new hit for future drug design studies in Chagas disease.
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New derivatives from dehydrodieugenol B and its methyl ether displayed high anti-Trypanosoma cruzi activity and cause depolarization of the plasma membrane and collapse the mitochondrial membrane potential
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| Autor/in / Beteiligte Person: | Galhardo, Thalita S ; Ueno, Anderson K ; Costa-Silva, Thaís A ; Tempone, André G ; Carvalho, Wagner A ; Fischmeister, Cedric ; Bruneau, Christian ; Mandelli, Dalmo ; Lago, João Henrique G ; Universidade Federal do ABC = Federal University of ABC = Université Fédérale de l'ABC Brazil (UFABC) ; Federal University of Sao Paulo (Unifesp) ; Instituto Adolfo Lutz São Paulo, Brazil ; Institut des Sciences Chimiques de Rennes (ISCR) ; Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes) ; Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie - CNRS Chimie (INC-CNRS)-Centre National de la Recherche Scientifique (CNRS) ; The authors acknowledge CAPES−COFECUB for support to the project no. PHC 884-17 (France) and 883/2017 (Brazil), CNPq (project 312288/2019-0 and 404843/2018-2) ; FAPESP (2021/02789-7, 2021/04464-8, 2018/01258-5, 2018/07885-1, 2018/10279-6, 2017/24931-4, 2017/17044-1, and 2016/05006-5), CAPES (Finance Code 001), Institutional Internationalization Program CAPES-PrInt/UFABC and the Multi-User Central Facilities (CEM/UFABC) for the experimental support. J.H.G.L., A.G.T. and D.M. also thank CNPq for fellowships. Finally, T. S. G. thanks the CAPES−COFECUB grant 88887.198050/2018-00. |
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| Zeitschrift: | ISSN: 0009-2797 ; Chemico-Biological Interactions ; https://hal.science/hal-03798572 ; Chemico-Biological Interactions, 2022, 366, pp.110129. ⟨10.1016/j.cbi.2022.110129⟩, 2022 |
| Veröffentlichung: | HAL CCSD ; Elsevier, 2022 |
| Medientyp: | academicJournal |
| DOI: | 10.1016/j.cbi.2022.110129 |
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