Synthesis, antiprotozoal activity and cytotoxicity in U-937 macrophages of triclosan–hydrazone hybrids

Abstract

The synthesis and biological activities (cytotoxicity, leishmanicidal, and trypanocidal) of 11 triclosan-hydrazone hybrids are described herein. The structure of the products was elucidated by spectral data (NMR, IR) and mass spectrometric analyses. The synthesized compounds were evaluated against amastigotes forms of L. (V) panamensis, which is the most prevalent Leishmania species in Colombia, and against Trypanosoma cruzi, which is the major pathogenic species to Chagas disease in humans. In addition, the cytotoxic activity of the synthesized compounds was evaluated against human U-937 macrophages. Hydrazone hybrids were obtained as Esynperiplanar and E-antiperiplanar conformers. Nine of them were active against L. (V) panamensis (5a-5d, 5f-5j) and eight of them against T. cruzi (5a, 5c, 5d, 5f-5j), with EC 50 values lower than 40 µM. The compounds 5c, 5e, and 5h exhibit the best selectivity index against both L. (V) panamensis and T. cruzi, with values ranging from 5.90 to 16.55, thus showing potential as starting compounds for the eventual development of drugs against these parasites. The presence of hydroxy or methoxy groups in positions 2 and 4 of the aromatic ring of the benzylidene moiety increases both activity and cytotoxicity. There is no clear relationship between the antiprotozoal activity and the methylation pattern of the hydroxy groups, since in some cases methylation decreases the activity (5d vs. 5g) while in other cases the activity is increased (5c vs. 5f and 5i vs. 5j).

Design, Synthesis, and Biological Evaluation of Pyridazinones Containing the (2-Fluorophenyl) Piperazine Moiety as Selective MAO-B Inhibitors

“…In addition, the carbons of pyridazinone C 6 , pyridazinone C 4 , and 2-fluorophenyl C 5 were double in 13 C-NMR spectrum at low MHz ( Figure 1 C). These pairs of signals clearly show that these compounds exist in two stereoisomeric forms, as other isomers described previously [ 32 , 33 ].…”

New phenoxyacetohydrazones against Trypanosoma cruzi

“…The synthetic route planned to achieve the NAH targets compounds (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19) consists in three steps. To a suspension of phenol (20) and potassium carbonate in acetonitrile, was added methyl bromoacetate (21) and the reaction was warmed till re ux to furnish methyl 2-phenoxyacetate ( 22) in 96% yield [21].…”

“…The hydrazinolysis of the ester furnished the key N-acylhydrazide intermediate ( 23) in 95% yield [22]. Finally, the target compounds (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19), were obtained by addition to carbonyl followed by the elimination of water between the N-acylhydrazide ( 23) and the corresponding aromatic aldehydes (Het/ArCHO) in water, using hydrochloric acid as catalyst described in Scheme 1 [17,23].…”

“…The in vitro screening using trypomastigote revealed 11, with an 3,4-dihydroxyphenyl group attached to the imine unit, as the most active compound with an IC 50 /24 h= 10.3 µM, equivalent to benznidazole, the reference drug. In order to evaluate the contribution of its hydroxyl groups at C-3 and at C-4, we compared its activity with different analogues ; 3,4-OCH 3 (12); 3-OCH 3 , 4-OH ( 13); 3-OH, 4-OCH 3 (14) and -O-CH 2 -O-( 16)]. We observed an important decrease in the activity, indicating that the two hydroxyl groups in the catechol subunit present a pharmacophoric characteristic against T. cruzi.…”

Furanchalcone–biphenyl hybrids: synthesis, in silico studies, antitrypanosomal and cytotoxic activities

“…showing EC 50 values of 1.10 µM and 4.6 µM, respectively [16,17]. Quinoline-chalcone hybrid 2e also exhibited trypanocidal activity with a value of 31.73 µM [18].…”