O(2)-dependent efficacy of novel piperidine- and piperazine-based chalcones against the human parasite Giardia intestinalis.

Abstract

Giardia intestinalis is the most frequent protozoan agent of intestinal diseases worldwide. Though commonly regarded as an anaerobic pathogen, it preferentially colonizes the fairly oxygen-rich mucosa of the proximal small intestine. Therefore, when testing new potential antigiardial drugs, O2 should be taken into account, since it also reduces the efficacy of metronidazole, the gold standard drug against giardiasis. In this study, 46 novel chalcones were synthesized by microwave-assisted Claisen-Schmidt condensation, purified, characterized by high-resolution mass spectrometry, (1)H and (13)C nuclear magnetic resonance, and infrared spectroscopy, and tested for their toxicity against G. intestinalis under standard anaerobic conditions. As a novel approach, compounds showing antigiardial activity under anaerobiosis were also assayed under microaerobic conditions, and their selectivity against parasitic cells was assessed in a counterscreen on human epithelial colorectal adenocarcinoma cells. Among the tested compounds, three [30(a), 31(e), and 33] were more effective in the presence of O2 than under anaerobic conditions and killed the parasite 2 to 4 times more efficiently than metronidazole under anaerobiosis. Two of them [30(a) and 31(e)] proved to be selective against parasitic cells, thus representing potential candidates for the design of novel antigiardial drugs. This study highlights the importance of testing new potential antigiardial agents not only under anaerobic conditions but also at low, more physiological O2 concentrations.

• Authors: Vijay Bahadur, Daniela Mastronicola, Hemandra Kumar Tiwari, Yogesh Kumar, Micol Falabella, Leopoldo Paolo Pucillo, Paolo Sarti, Alessandro Giuffrè, Brajendra Kumar Singh
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 58 Issue 1 Pg. 543-9 ( 2014) ISSN: 1098-6596 [Electronic] United States
• PMID: 24217695 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antiprotozoal Agents
• Chalcones
• Piperazines
• Piperidines
• Piperazine
• piperidine

Topics

• Antiprotozoal Agents (adverse effects, chemistry, pharmacology)
• Caco-2 Cells
• Cell Survival (drug effects)
• Chalcones (adverse effects, chemistry, pharmacology)
• Giardia lamblia (drug effects)
• Humans
• Piperazine
• Piperazines (chemistry)
• Piperidines (chemistry)