Synthesis, Leishmanicidal and Cytotoxic Activity of Triclosan-Chalcone, Triclosan-Chromone and Triclosan-Coumarin Hybrids

Abstract

Twelve hybrids derived from triclosan were obtained via Williamson etherification of O-triclosan alkyl bromide plus chalcone and O-coumarin or O-chromone alkyl bromide plus triclosan, respectively. Structures of the products were elucidated by spectroscopic analysis. The synthesized compounds were evaluated for antileishmanial activity against L. (V) panamensis amastigotes. Cytotoxic activity was also evaluated against mammalian U-937 cells. Compounds 7-9 and 17, were active against Leishmania parasites (EC 50 = 9.4; 10.2; 13.5 and 27.5 µg/mL, respectively) and showed no toxicity toward mammalian cells (>200 µg/mL). They are potential candidates for antileishmanial drug development. Compounds 25-27, were active and cytotoxic. Further studies using OPEN ACCESSMolecules 2014, 19 13252 other cell types are needed in order to discriminate whether the toxicity shown by these compounds is against tumor or non-tumor cells. The results indicate that compounds containing small alkyl chains show better selectivity indices. Moreover, Michael acceptor moieties may modify both the leishmanicidal activity and cytotoxicity. Further studies are required to evaluate if the in vitro activity against Leishmania panamensis demonstrated here is also observed in vivo.

Synthesis, leishmanicidal, trypanocidal and cytotoxic activities of quinoline-chalcone and quinoline-chromone hybrids

“…Initially, 7-hydroxychromone was treated with potassium hydroxide and 1,ω-dibromoalkanes (ω = 3, 4, 5, 7, 9 and 12) to obtain the respective bromoalkyl derivatives 15-19 in yields similar to previous reports (Otero et al, 2014;Li et al, 2013) but in significantly shorter times. These compounds were coupled with quinoline to produce compounds 20-24 in 34-70% yields.…”

“…Quinoline-chalcone hybrids 8-13 were obtained via microwave assisted Williamson etherification (Peng et al, 2002;Otero et al, 2014) between bromoalkylquinoline 2-7 and 3,4-dimethoxy-4'-hydroxychalcone. Reaction yields ranged between 44% and 65%.…”

Synthesis, leishmanicidal, trypanocidal and cytotoxic activity of quinoline-hydrazone hybrids

“…An electrophilic conjugated system could be generated from o-hydroxybenzylidene-N-acylhydrazone framework due to the ability of this system to be converted into an electrophilic quinone methide intermediate through a pericyclic rearrangement [38]. This mechanism has been reported for other α,β-unsaturated compounds such as lactones, chromones and cinnamic acid esters [39][40][41].…”

Antiprotozoal activity and cytotoxicity of extracts from Solanum arboreum and S. ovalifolium (Solanaceae)

“…These compounds could participate in a conjugated addition of nucleophilic amino acid residues present in target enzymes such as cysteine proteases on leishmania (Mottram et al, 2004) in a Michael type mechanism. This mechanism has been reported for other α,β-unsaturated compounds such as lactones and chromones Otero et al, 2014).…”