Design, synthesis and biological evaluation of new aryl thiosemicarbazone as antichagasic candidates

作者：Blau Lorena^*; Menegon Renato Farina; Trossini Gustavo H G; Dutra Molino Joao Vitor; Vital Drielli Gomes; Barretto Cicarelli Regina Maria; Passerini Gabriela Duo; Bosquesi Priscila Longhin; Chin Chung Man

来源：European Journal of Medicinal Chemistry, 2013, 67: 142-151.

DOI：10.1016/j.ejmech.2013.04.022

• Chagas disease
• Thiosemicarbazone
• Oxidative stress
• Cruzain
• Docking
• Mutagenicity

The present work reports on the synthesis, biological assaying and docking studies of a series of 12 aryl thiosemicarbazones, which were planned to act over two main enzymes, cruzain and trypanothione reductase. These enzymes are used as targets of trypanocidal activity in Chagas disease control with a minimal mutagenic profile. Three p-nitroaromatic thiosemicarbazones showed high activity against Ttypanosoma cruzi in in vitro assays (IC50 < 57 mu M), and no mutagenic profile was observed in micro-nucleous tests. Although the in vitro inhibition test showed that 10-mu M doses of eight compounds inhibited cruzain activity, no correlation was found between cruzain inhibition and trypanocidal activity.

• 出版日期2013-9