Symmetrical and unsymmetrical substituted 2,5-diarylidene cyclohexanones as anti-parasitic compounds

Author(s)

Din, Zia Ud ^{[1, 2]} ; Trapp, Marilia Almeida ^[1] ; de Medeiros, Livia Soman ^[1] ; Lazarin-Bidoia, Danielle ^[3] ; Garcia, Francielle Pelegrin ^[3] ; Peron, Francieli ^[3] ; Nakamura, Celso Vataru ^[3] ; Rodriguez, Ihosvany Camps ^[4] ; Wadood, Abdul ^[5] ; Rodrigues-Filho, Edson ^[1]

Affiliation

^[1] Univ Fed Sao Carlos, Dept Chem, LaBioMMi, CP 676, BR-13565905 Sao Carlos, SP - Brazil

^[2] Woman Univ Swabi, Dept Chem, Swabi 23340, KP - Pakistan

^[3] Univ Estadual Maringa, Lab Inovacao Tecnol Desenvolvimento Farmacos & Co, Ave Colombo 5790, Bloco B-08, BR-87020900 Maringa, PR - Brazil

^[4] Univ Fed Alfenas UNIFAL MG, Inst Ciencias Exatas ICEx, Lab Modelagem Computac LaModel, Ave Jovino Fernandes Sales S-N, BR-37130000 Alfenas, MG - Brazil

^[5] Abdul Wali Khan Univ Mardan, Dept Biochem, Mardan 23200 - Pakistan

• Document type: Journal article
• Source: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY; v. 155, p. 596-608, JUL 15 2018.
• Web of Science Citations: 1

Abstract

Symmetrical and unsymmetrical bis-aryl-alpha,beta-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 mu M. 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 mu M, while five compounds exhibited activity from 15.0 +/- 1.4 to 30.2 +/- 1.8 mu M 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. (C) 2018 Elsevier Masson SAS. All rights reserved. (AU)

• FAPESP's process: 10/11384-6 - Biotransformation of natural and synthetic products using endophytic microorganisms, a chemical-ecologycal approach for the production of bioactive substances
• Grantee: Edson Rodrigues Filho
• Support Opportunities: Regular Research Grants