2. Academic Validation
  3. Synthesis, Anthelmintic Activity, and Mechanism of Action of 5-Aryl-1 H-indoles

Synthesis, Anthelmintic Activity, and Mechanism of Action of 5-Aryl-1 H-indoles

  • J Agric Food Chem. 2025 Dec 31;73(52):33059-33069. doi: 10.1021/acs.jafc.5c14071.
Alena Kadlecová 1,  Karolina Dzedulionytė Müldür 2 3,  Miroslav Peřina 1,  Kristýna Bieleszová 4,  Chao Zhang 5,  Daniel Kováříček 4,  Elora Valderas-García 6,  Dominik Vítek 7,  Miglė Valikonytė 2,  Algirdas Šačkus 2,  Joana Solovjova 2,  Vida Malinauskienė 2,  Karel Doležal 4 5,  Ondřej Novák 5,  Florian M W Grundler 8,  Peter Roy 9,  Maria Martínez-Valladares 8,  Jiří Voller 1 7,  A Sylvia S Schleker 8,  Asta Žukauskaitė 4
Affiliations

Affiliations

  • 1 Depatment of Experimental Biology, Faculty of Science, Palacký University, Šlechtitelů 27, CZ-77900 Olomouc, Czech Republic.
  • 2 Department of Organic Chemistry, Kaunas University of Technology, Radvilėnu pl. 19, LT-50254 Kaunas, Lithuania.
  • 3 Department of Pharmaceutical Sciences, Division of Pharmaceutical Chemistry, Faculty of Life Sciences, University of Vienna, Josef-Holaubek-Platz 2, A-1090 Vienna, Austria.
  • 4 Department of Chemical Biology, Faculty of Science, Palacký University, Šlechtitelů 27, CZ-77900 Olomouc, Czech Republic.
  • 5 Laboratory of Growth Regulators, Institute of Experimental Botany, The Czech Academy of Sciences & Faculty of Science, Palacký University, Šlechtitelů 27, CZ-77900 Olomouc, Czech Republic.
  • 6 Instituto de Ganadería de Montaña (CSIC-Universidad de León), Departamento de Sanidad Animal, Grulleros, ES-24346 León, Spain.
  • 7 Institute of Molecular and Translational Medicine, Faculty of Medicine, Palacký University, CZ-77515 Olomouc, Czech Republic.
  • 8 INRES - Molecular Phytomedicine, University Bonn, Karlrobert-Kreiten-Str. 13, D-53115 Bonn, Germany.
  • 9 Department of Molecular Genetics & Department of Pharmacology & Toxicology, University of Toronto, The Donnelly Centre, Rm 1202 160 College St., ON M5S 3E1 Toronto, Canada.
PMID: 41401077 DOI: 10.1021/acs.jafc.5c14071
Abstract

Parasitic nematodes are a significant concern in human and veterinary medicine as well as agriculture. In this study, we prepared twenty-seven 5-phenyl-1H-indole derivatives bearing various substituents on the phenyl ring and assessed their efficacy against nematodes. Using Caenorhabditis elegans, we selected the most potent compounds and evaluated their toxicity on selected animal and plant-parasitic nematode species. Compounds featuring 4-chloro, 4-fluoro, and 4-trifluoromethoxy groups on the phenyl ring inhibited the motility of exsheathed L3 larvae of Hemonchus contortus while exhibiting limited cytotoxicity in mammalian cell cultures. These compounds showed similar effects against the plant-parasitic nematodes Heterodera schachtii and Ditylenchus destructor, albeit with reduced potency. We propose that the compounds might act as inhibitors of mitochondrial complex II as inferred from molecular modeling, decreased mitochondrial membrane potential, and reduced activity in C. elegans complex II mutants.

Keywords

C. elegans; SDH inhibitor; indole; mitochondrial complex II; parasitic nematodes.

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