Aromatic glycosyl disulfide derivatives: Evaluation of their inhibitory activities against Trypanosoma cruzi

详细信息    查看全文

• 作者：Bessy Gutié ; rrez^a ; Christian Muñ ; oz^a ; Luis Osorio^a ; Krisztina Fehé ; r^b ; T&uuml ; nde-Zita Illyé ; s^c ; Zsuzsa Papp^c ; Ambati Ashok Kumar^c ; Katalin E. Kö ; vé ; r^c ; Herná ; n Sagua^a ; Jorge E. Araya^a ; Patricio Morales^d ; Lá ; szló ; Szilá ; gyi^c ; ^{lszilagyi@unideb.hu} ; Jorge Gonzá ; lez^a ; ^{jgonzalez@uantof.cl}
• 关键词：SDFVZUPHBRAFNX-XYGWXUJBSA-N ; QBQGHUWKYXMVED-IJTJVXSJSA-N ; RANXBKQGNYWKHN-XUYUUWNASA-N ; RANXBKQGNYWKHN-IQUPQFMESA-N ; WLLZLSXZYIMQQC-XUYUUWNASA-N ; WLLZLSXZYIMQQC-IQUPQFMESA-N ; JLSAVDGVJNUFQH-IQUPQFMESA-N ; BAORVJMPOKICFI-GTHRRLHISA-N ; BAORVJMPOKICFI-XBSSEPBX
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2013
• 出版时间：15 June, 2013
• 年：2013
• 卷：23
• 期：12
• 页码：3576-3579
• 全文大小：503 K

文摘

Aromatic oligovalent glycosyl disulfides and some diglycosyl disulfides were tested against three different Trypanosoma cruzi strains. Di-(¦Â-d-galactopyranosyl-dithiomethylene) benzenes 2b and 4b proved to be the most active derivatives against all three strains of cell culture-derived trypomastigotes with IC₅₀ values ranging from 4 to 11 ¦ÌM at 37 ¡ãC. The inhibitory activities were maintained, although somewhat lowered, at a temperature of 4 ¡ãC as well. Three further derivatives displayed similar activities against at least one of the three strains. Low cytotoxicities of the active compounds, tested on confluent HeLa, Vero and peritoneal macrophage cell cultures, resulted in significantly higher selectivity indices (SI) than that of the reference drug benznidazole. Remarkably, several molecules of the tested panel strongly inhibited the parasite release from T. cruzi infected HeLa cell cultures suggesting an effect against the intracellular development of T. cruzi amastigotes as well.