2. Academic Validation
  3. Anthelmintic efficacy evaluation and mechanism of N-methylbenzo[d]oxazol-2-amine

Anthelmintic efficacy evaluation and mechanism of N-methylbenzo[d]oxazol-2-amine

  • Sci Rep. 2023 Dec 21;13(1):22840. doi: 10.1038/s41598-023-50305-y.
Pattaneeya Prangthip # 1,  Jumreang Tummatorn # 2 3,  Poom Adisakwattana 4,  Naphatsamon Uthailak 5,  Usa Boonyuen 6,  Phornpimon Tipthara 7,  Joel Tarning 7 8,  Pavitra Laohapaisan 2,  Charnsak Thongsornkleeb 2 3,  Somsak Ruchirawat 2 3,  Onrapak Reamtong 9
Affiliations

Affiliations

  • 1 Department of Tropical Nutrition and Food Science, Faculty of Tropical Medicine, Mahidol University, Bangkok, 10400, Thailand.
  • 2 Program on Chemical Sciences, Chulabhorn Graduate Institute, Center of Excellence on Environmental Health and Toxicology (EHT), OPS, MHESI, 54 Kamphaeng Phet 6, Laksi, Bangkok, 10210, Thailand.
  • 3 Laboratory of Medicinal Chemistry, Chulabhorn Research Institute, 54 Kamphaeng Phet 6, Laksi, Bangkok, 10210, Thailand.
  • 4 Department of Helminthology, Faculty of Tropical Medicine, Mahidol University, Bangkok, 10400, Thailand.
  • 5 Department of Social and Environmental Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, 10400, Thailand.
  • 6 Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University, Bangkok, 10400, Thailand.
  • 7 Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, 10400, Thailand.
  • 8 Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.
  • 9 Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University, Bangkok, 10400, Thailand. onrapak.rea@mahidol.ac.th.
  • # Contributed equally.
PMID: 38129499 DOI: 10.1038/s41598-023-50305-y
Abstract

Parasitic roundworms cause significant sickness and mortality in Animals and humans. In livestock, these nematodes have severe economic impact and result in losses in food production on a global scale. None of the currently available drugs ideally suit all treatment circumstances, and the development of drug-resistant nematode strains has become a challenge to control the Infection. There is an urgent need to develop novel anthelmintic compounds. According to our previous report, N-methylbenzo[d]oxazol-2-amine (1) showed anthelmintic activity and lowest cytotoxicity. In this study, in vivo anthelmintic properties were evaluated using Trichinella spiralis infected mice. Toxicity was evaluated using the rats and mode of action using molecular docking and metabolomics approaches. The in vivo results demonstrate that a dose of 250 mg/kg reduced the T. spiralis abundance in the digestive tract by 49%. The 250 mg/kg Albendazole was served as control. The relatively low acute toxicity was categorized into chemical category 5, with an LD50 greater than 2000 mg/kg body. Molecular docking analysis showed the T. spiralis tubulin beta chain and glutamate-gated channels might not be the main targets of compound 1. Metabolomics analysis was used to explain the effects of compound 1 on the T. spiralis adult worm. The results demonstrated that compound 1 significantly up-regulated the metabolism of purine, pyrimidine and down-regulated sphingolipid metabolism. In conclusion, compound 1 could be a potential molecule for anthelmintic development. The bioavailability, pharmacokinetics, and absorption of this compound should be studied further to provide information for its future efficacy improvement.

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