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

详细信息    查看全文

• 作者：Lorena Blau ; Renato Farina Menegon ; Gustavo H.G. Trossini ; Jo?o Vitor Dutra Molino ; Drielli Gomes Vital ; Regina Maria Barretto Cicarelli ; Gabriela Du¨® Passerini ; Priscila Longhin Bosquesi ; Chung Man Chin
• 关键词：Chagas disease ; Thiosemicarbazone ; Oxidative stress ; Cruzain ; Docking ; Mutagenicity
• 刊名：European Journal of Medicinal Chemistry
• 出版年：2013
• 出版时间：September, 2013
• 年：2013
• 卷：67
• 期：Complete
• 页码：142-151
• 全文大小：1281 K

文摘

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 Trypanosoma cruzi in in?vitro assays (IC₅₀?<?57?¦ÌM), and no mutagenic profile was observed in micronucleous tests. Although the in?vitro inhibition test showed that 10-¦ÌM doses of eight compounds inhibited cruzain activity, no correlation was found between cruzain inhibition and trypanocidal activity.