Organometallic Derivatization of the Nematocidal Drug Monepantel Leads to Promising Antiparasitic Drug Candidates
| Autor: | Patrick Mac, Gilles Gasser, Sandro Konatschnig, Robin B. Gasser, Malay Patra, Abdul Jabbar, Jeannine Hess, Loganathan Rangasamy, Erik M. Jorgensen, Olivier Blacque |
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| Přispěvatelé: | University of Zurich, Gasser, Robin B |
| Rok vydání: | 2016 |
| Předmět: |
10120 Department of Chemistry
0301 basic medicine Antinematodal agent 1503 Catalysis Antiparasitic medicine.drug_class Drug Resistance Crystallography X-Ray Catalysis 03 medical and health sciences chemistry.chemical_compound 540 Chemistry medicine Aminoacetonitrile Animals Organic chemistry Anthelmintic Derivatization Antiparasitic Agents biology Antinematodal Agents Bioorganometallic chemistry Organic Chemistry General Chemistry Potentiator biology.organism_classification Antiparasitic agent 3. Good health 030104 developmental biology chemistry Haemonchus 1605 Organic Chemistry Haemonchus contortus medicine.drug |
| Zdroj: | Chemistry – A European Journal. 22:16602-16612 |
| ISSN: | 1521-3765 0947-6539 |
| DOI: | 10.1002/chem.201602851 |
| Popis: | The discovery of novel drugs against animal parasites is in high demand due to drug-resistance problems encountered around the world. Herein, the synthesis and characterization of 27 organic and organometallic derivatives of the recently launched nematocidal drug monepantel (Zolvix®) are described. The compounds were isolated as racemates and were characterized by 1H, 13C, and 19F NMR spectroscopy, mass spectrometry, and IR spectroscopy, and their purity was verified by microanalysis. The molecular structures of nine compounds were confirmed by X-ray crystallography. The anthelmintic activity of the newly designed analogues was evaluated in vitro against the economically important parasites Haemonchus contortus and Trichostrongylus colubriformis. Moderate nematocidal activity was observed for nine of the 27 compounds. Three compounds were confirmed as potentiators of a known monepantel target, the ACR-23 ion channel. Production of reactive oxygen species may confer secondary activity to the organometallic analogues. Two compounds, namely, an organic precursor (3 a) and a cymantrene analogue (9 a), showed activities against microfilariae of Dirofilaria immitis in the low microgram per milliliter range. |
| Databáze: | OpenAIRE |
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