Premium
Synthesis, In Vitro Antiprotozoal Activity and Cytotoxicity of New Thymol Carbonate Derivatives
Author(s) -
Clemente Camila M.,
Ravetti Soledad,
Allemandi Daniel A.,
Hergert Lisandro Y.,
Pineda Tatiana,
Robledo Sara M.
Publication year - 2021
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.202101461
Subject(s) - thymol , antiprotozoal , antiparasitic , cytotoxicity , chemistry , antiparasitic agent , trypanosoma cruzi , trypanocidal agent , hemozoin , in vitro , bioavailability , pharmacology , biochemistry , biology , essential oil , trypanosoma brucei , medicine , chromatography , parasite hosting , heme , pathology , world wide web , computer science , gene , enzyme
Abstract Considering the biological properties of thymol and its derivatives and the urgency of effective drugs for neglected tropical diseases, we report the synthesis of a novel series of carbonates of thymol, using N,N‐carbonyldiimidazole and several aliphatic alcohols. The in vitro leishmanicidal, trypanocidal, antiplasmodial and cytotoxic activities of thymol and derivatives were also studied together with the in silico physicochemical and pharmacokinetic properties of synthesized compounds. Both, thymol and carbonate derivatives although were cytotoxic to mammal U‐937 cells, they were also highly active against Plasmodium falciparum and Trypanosoma cruzi parasites. When relating the cytotoxicity with antiparasitic activity all compounds, except 1 g and 1 i were more selective against parasites than against the mammal cells. Computational analysis indicates good oral bioavailability for all compounds. Results suggest that thymol and their carbonate derivatives have promising therapeutic potential as antiplasmodial, trypanocidal and leishmanicidal agents; nonetheless further studies are needed to validate their efficacy as antiparasitic drugs in in vivo assays.