Antitubercular activity of 1,2,3-triazolyl fatty acid derivatives

Abstract

A collection of 1,2,3-triazoles unsaturated fatty acid mimics were efficiently synthesized by click chemistry. The 1,4-disubstituted analogs prepared covered different alkyl chain lengths and triazole positions. The compounds were subsequently tested against Mycobacterium tuberculosis, being most of them active with some of the analogs displaying activity at micromolar concentration. The most potent member of the series has the triazole moiety on the C-2 position with a carbon chain of eight or ten carbon atoms. The 1,5-isomers of the most active analog were significantly less active than the original isomer. The activity of the selected hit was assayed on several clinical MTB multi-drug resistant strains providing the same MIC.

Exploring the chemical space of 1,2,3-triazolyl triclosan analogs for discovery of new antileishmanial chemotherapeutic agents

“…We have previously reported bioactive 1,2,3-triazolyl derivatives against Leishmania parasite (amino sterols) and M. tuberculosis (fatty acids derivatives). 16,17 In this opportunity, our aim was to develop novel structures inspired on the structures of TRC and 8PP, to find new chemical entities as candidates for antileishmanial drug discovery. The presence of putative enoyl-ACP reductase encoding genes in Leishmania prompted us to prepare and assay a library of 1,4 disubstituted 1,2,3-triazolyl catechols.…”

“…Antimycobacterial activity was determined by two-fold dilution of the compounds in Middlebrook 7H9-ADS-Gly medium as described previously. 16 For 6 Colony Forming Units) was used to inoculate the wells. Plates were sealed with Parafilm and incubated at 37°C for five days.…”

4-(4-(((1H-Benzo[d][1,2,3]triazol-1-yl)oxy)methyl)-1H-1,2,3-triazol-1-yl)-7-chloroquinoline

“…In this connection, the nitrogen containing heterocycles are found in abundance in most of the medicinal compounds. In particular, triazoles are five-membered rings, which contain two carbon and three nitrogen atoms and many covalently linked triazole hybrids exhibits diverse biological activities, such as anti-inflammatory [13], anticancer [14], antibacterial [15], and antitubercular [16] (Figure 1a-l).…”

Preparation of chiral β-hydroxytriazoles in one-pot chemoenzymatic bioprocesses catalyzed by Rhodotorula mucilaginosa

“…Azole compounds have been extensively studied as potential targets for drug discovery since they possess a broad range of biological properties, including antimicrobial, antiviral, antiepileptic, anti -HIV [12]. In particular, 1,2,3-triazoles are active against tuberculosis [13][14][15]. Besides, βhydroxytriazole derivatives, specifically the R enantiomers, have been reported as potential βadrenergic receptor blockers [16,17].…”