دورية أكاديمية
أعرض في EDS

Molecular interaction analysis of the lignans from Piper cubeba in complex with Haemonchus contortus phosphomethyltransferase.

التفاصيل البيبلوغرافية
العنوان: Molecular interaction analysis of the lignans from Piper cubeba in complex with Haemonchus contortus phosphomethyltransferase.
المؤلفون: Borges A; Universidade Estadual Paulista, Departamento de Física e Química, Faculdade de Engenharia de Ilha Solteira, Ilha Solteira, SP, Brazil; Faculdade de Medicina, Centro Universitário de Santa Fé do Sul - UNIFUNEC, Santa Fé do Sul, SP, Brazil., de Oliveira IP; Universidade Federal de Minas Gerais, Instituto de Ciências Agrícolas, Montes Claros, MG, Brazil., Lescano CH; Universidade de Campinas, Faculdade de Ciências Médicas, Campinas, SP, Brazil., Parreira RLT; Universidade de Franca, Centro de Pesquisas em Ciências Exatas e Tecnológicas, Franca, SP, Brazil., Orenha RP; Universidade de Franca, Centro de Pesquisas em Ciências Exatas e Tecnológicas, Franca, SP, Brazil., da Silva de Laurentiz R; Universidade Estadual Paulista, Departamento de Física e Química, Faculdade de Engenharia de Ilha Solteira, Ilha Solteira, SP, Brazil. Electronic address: rosangela.laurentiz@unesp.br.
المصدر: Veterinary parasitology [Vet Parasitol] 2023 Sep; Vol. 321, pp. 110001. Date of Electronic Publication: 2023 Aug 01.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier Country of Publication: Netherlands NLM ID: 7602745 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-2550 (Electronic) Linking ISSN: 03044017 NLM ISO Abbreviation: Vet Parasitol Subsets: MEDLINE
أسماء مطبوعة: Publication: Amsterdam : Elsevier
Original Publication: Amsterdam : Elsevier Scientific Pub. Co.
مواضيع طبية MeSH: Haemonchus* , Piper* , Lignans*/pharmacology , Nematoda* , Anthelmintics*/pharmacology, Animals ; Molecular Docking Simulation ; Phosphorylcholine/pharmacology ; Larva ; Mammals
مستخلص: In vitro larvicidal assays carried out previously by our research group with cubebin, dihydrocubebin and hinokinin, lignans extracted from the fruits of Piper cubeba, against Haemonchus contortus larvae showed strong action larvicidal these compounds. Hinokinin was the most active (EC 50 = 0.34 µg/mL) with strong action on the cuticle of the larvae as observed by scanning electron microscopy of the L3 stage. Therefore, to understand the mechanism of action of these compounds in silico studies were carried out using the enzyme phosphomethyltransferase of Haemonchus contortus that contain PMT-1 and PMT-2 di-domains responsible for phosphocholine synthesis, which is one of the main lipids in nematodes. This pathway is not found in mammals, so this enzyme is an important biological target for the development of new anthelmintics. Results of molecular docking, molecular dynamic and a density functional theory calculations studies with the three lignans show few interactions with PMT-1. However, hinokinin has important interactions with PMT-2, that can deactivate the enzyme and interrupt the phosphocholine synthesis, which is an essential compound for the development and maintenance of the nematode cuticle and its survive. Therefore, the previous results of the in vitro assay allied with in silico results, now realized; suggest that hinokinin may be a possible selective target for the development of new anthelmintics against Haemonchus contortus since the PMT-2 domain is present in this nematode.
Competing Interests: Declaration of Competing Interest None.
(Copyright © 2023 Elsevier B.V. All rights reserved.)
فهرسة مساهمة: Keywords: Haemonchus contortus; Lignans; Molecular docking; Molecular dynamic; Theoretical calculations
المشرفين على المادة: 26543-89-5 (hinokinin)
107-73-3 (Phosphorylcholine)
0 (Lignans)
0 (Anthelmintics)
تواريخ الأحداث: Date Created: 20230807 Date Completed: 20230831 Latest Revision: 20230831
رمز التحديث: 20231215
DOI: 10.1016/j.vetpar.2023.110001
PMID: 37549491
قاعدة البيانات: MEDLINE
الوصف
تدمد:1873-2550
DOI:10.1016/j.vetpar.2023.110001