Synthesis and Biological Evaluation of New Eugenol-Derived 1,2,3-Triazoles as Antimycobacterial Agents

Abstract

Eugenol has diverse biological properties including antimycobacterial activity, and the triazole ring is an important heterocycle in antimycobacterial compounds. Therefore, this research aimed to synthesize novel eugenol-derived 1,2,3-triazole as antimycobacterial agents with interesting cytotoxic profile and pharmacological assets. Sixteen compounds were obtained and characterized by nuclear magnetic resonance (NMR), infrared (IR), and high-resolution mass spectrometry (HRMS). Among them, the best growth inhibition properties from a microdilution assay were observed for three derivatives: a benzylic ether (minimum inhibitory concentration (MIC) = 48.89 µM) against Mycobacterium abscessus (ATCC 19977), an O-galactosyde (MIC = 31.76 µM) against Mycobacterium massiliense (ATCC 48898) and a sulfonate (MIC = 88.64 µM) against Mycobacterium fortuitum (ATCC 6841). They can form biofilms, and the infection progression is challenging to control due to multi-drug resistance profiles against diverse antibiotics. In conclusion, the above-mentioned compounds represent starting points in the search of bioactive molecules against mycobacteria with low cytotoxicity and better pharmacological profiles.

Design, Synthesis, Antimicrobial Evaluation and in Silico Studies of Eugenol‐Sulfonamide Hybrids

“…Pharmacological properties of eugenol have been extensively highlighted, especially involving its antibacterial and antifungal properties [17–22] . Our research group has previously demonstrated that synthetic compounds obtained from natural phenylpropanoids, such as eugenol or its analogs (dihydroeugenol and isoeugenol), have important antimicrobial activity and that hybrids obtained from phenylpropanoids and sulfonamide moieties have important antitumor activity [23–30] . Taking advantage of the molecular hybridization strategy (and the well‐established antibacterial potential of eugenol and sulfonamide‐based drugs separately) herein we present for the first time the antibacterial activity of eugenol and dihydroeugenol‐based hybrids bearing the sulfonamide functionality ( Scheme 1).…”

Preparation of Mechanically Robust Bio-Based Polyurethane Foams Using Depolymerized Native Lignin

“…Kraft lignin Indulin AT (KL) was obtained from Ingevity (North Charleston, SC, USA). Dihydroconiferyl alcohol (DCA) was prepared from eugenol by the reaction with borane dimethyl sulfide and oxidation with hydrogen peroxide as previously described . Information on chemicals used for analysis is provided in the Supporting Information.…”

Tailored Functionalization of Natural Phenols to Improve Biological Activity

“…Several examples are present in the literature about ( i ) O -alkylation of eugenol with terminal alkynes, followed by reaction with different benzyl azides [ 203 , 204 , 205 ]; ( ii ) eugenol conversion in epoxide and ring opening to obtain the corresponding alkyl azides, followed by reaction with different alkynes [ 206 ]; ( iii ) hydroboration oxidation at the allylic position of eugenol, followed by mesylation and azidation reactions, to achieve the eugenol azide; then, reaction with phenylacetylene to afford the triazole. Importantly, the first step of this latter process requires -OH protection trough silylation, thus allowing the synthesis of variously substituted products ( Scheme 18 ) [ 207 ].…”

“…Synthesized eugenol triazole derivatives showed leishmanicidal [ 205 ], antimycobacterial [ 207 ], trypanocidal [ 206 ], anticancer [ 203 ] as well as protease inhibitory [ 204 ] activity. Triazole eugenol glucosides also showed significant bactericidal activity and low toxicity to normal cells [ 208 ].…”

“… Synthesis of different eugenol triazole derivatives [ 207 ]. Abbreviations: TIPSCl = triisopropylsilyl chloride; TBAF = tetrabutylammonium fluoride.…”