非表示:
キーワード:
-
要旨:
Symmetrical and unsymmetrical bis-aryl-a,b-unsaturated ketones were synthesized in moderate to
excellent yield by treating cyclohexanone with various aldehydes. Dimethylammonium dimethylcarbamate
(DIMCARB) was used as both catalyst and reaction medium for the synthesis of monoarylidenes
cycloadduct intermediates, which was further used to produce diarylidene cyclohexanones. All the 34
compounds synthesized were evaluated for their anti-proliferative activity, particularly against promastigote
of Leishmania amazonensis, epimastigoteand trypomastigoteof Trypanosoma cruzi. Eighteen
compounds displayed anti-leishmanial activity against promastigotes of L. amazonensis with IC50 values
ranging from 2.8 to 10 mM. In addition, two compounds exhibited significant antitrypanosomal activity
against epimastigotes of T. cruzi with IC50 values of 5.2 ± 0.8 and 3.0 ± 0.0 mM, while five compounds
exhibited activity from 15.0 ± 1.4 to 30.2 ± 1.8 mM against trypomastigote of T. cruzi. Moreover, all compounds
were more selective against the parasites than the epithelial cells. The unsymmetrical compounds
16, 28, 30 and 33 can be considered as favorable anti-parasitic lead molecule having IC50 and EC50
values in the low-micromolar range, better than the reference drug benznidazole, and low cytotoxicity
against Vero cells. The potent compounds were screened in silico against 17 enzymes of T. cruzi and best
scoring were found against Dihydroorotate Dehydrogenase.
