Synthesis and structure-activity relationship study of pyrrolidine-oxadiazoles as anthelmintics against Haemonchus contortus.

Animals Anthelmintics / chemical synthesis Cell Line Haemonchus / drug effects Humans Molecular Structure Motor Activity / drug effects Oxadiazoles / chemical synthesis Parasitic Sensitivity Tests Pyrrolidines / chemical synthesis Stereoisomerism Structure-Activity Relationship
Anthelmintic Drug discovery Haemonchus contortus Pyrrolidine-oxadiazoles Structure-activity relationship

Journal

European journal of medicinal chemistry
ISSN: 1768-3254
Titre abrégé: Eur J Med Chem
Pays: France
ID NLM: 0420510

Informations de publication

Date de publication:
15 Mar 2020
Historique:
received: 05 12 2019
revised: 22 01 2020
accepted: 22 01 2020
pubmed: 6 2 2020
medline: 15 12 2020
entrez: 5 2 2020
Statut: ppublish

Résumé

Parasitic roundworms (nematodes) are significant pathogens of humans and animals and cause substantive socioeconomic losses due to the diseases that they cause. The control of nematodes in livestock animals relies heavily on the use of anthelmintic drugs. However, their extensive use has led to a widespread problem of drug resistance in these worms. Thus, the discovery and development of novel chemical entities for the treatment of parasitic worms of humans and animals is needed. Herein, we describe our medicinal chemistry optimization efforts of a phenotypic hit against Haemonchus contortus based on a pyrrolidine-oxadiazole scaffold. This led to the identification of compounds with potent inhibitory activities (IC

Identifiants

DOI: 10.1016/j.ejmech.2020.112100 PMID: 32018095
pubmed: 32018095
pii: S0223-5234(20)30067-2
doi: 10.1016/j.ejmech.2020.112100
pii:
doi:

Substances chimiques

Anthelmintics 0
Oxadiazoles 0
Pyrrolidines 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

112100

Informations de copyright

Copyright © 2020 Elsevier Masson SAS. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of competing interest The authors declare no conflict of interest.

Auteurs

Banfeng Ruan (B)

Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Melbourne, Victoria, 3052, Australia; Key Lab of Biofabrication of Anhui Higher Education, Institution Centre for Advanced Biofabrication, Hefei University, Hefei, 230601, PR China.

Yuezhou Zhang (Y)

Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Melbourne, Victoria, 3052, Australia; Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville, VIC, 3010, Australia; State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, 430070, China.

Solomon Tadesse (S)

Department of Pharmaceutical Chemistry and Pharmacognosy, School of Pharmacy, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia.

Sarah Preston (S)

Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville, VIC, 3010, Australia; School of Health and Life Sciences, Federation University, Ballarat, Victoria, 3353, Australia.

Aya C Taki (AC)

Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville, VIC, 3010, Australia.

Abdul Jabbar (A)

Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville, VIC, 3010, Australia.

Andreas Hofmann (A)

Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville, VIC, 3010, Australia.

Yaqing Jiao (Y)

Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville, VIC, 3010, Australia.

Jose Garcia-Bustos (J)

Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville, VIC, 3010, Australia.

Jitendra Harjani (J)

Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Melbourne, Victoria, 3052, Australia.

Thuy Giang Le (TG)

Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Melbourne, Victoria, 3052, Australia.

Swapna Varghese (S)

Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Melbourne, Victoria, 3052, Australia.

Silvia Teguh (S)

Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Melbourne, Victoria, 3052, Australia.

Yiyue Xie (Y)

Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Melbourne, Victoria, 3052, Australia.

Jephthah Odiba (J)

Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Melbourne, Victoria, 3052, Australia.

Min Hu (M)

State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, 430070, China.

Robin B Gasser (RB)

Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville, VIC, 3010, Australia.

Jonathan Baell (J)

Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Melbourne, Victoria, 3052, Australia; School of Pharmaceutical Sciences, Nanjing Tech University, No. 30, South Puzhu Road, Nanjing, 211816, PR China; ARC Centre for Fragment-Based Design, Monash University, Parkville, VIC, 3052, Australia; Australian Translational Medicinal Chemistry Facility (ATMCF), Monash University, Parkville, Victoria, 3052, Australia. Electronic address: jonathan.baell@monash.edu.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Synthesis and structure-activity relationship...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Anti-infectieux › Antiparasitaires › Anthelminthiques › Synthesis and structure-activity relationship...
questionsmedicales.fr › Cellules › Cellules cultivées › Lignée cellulaire › Synthesis and structure-activity relationship...
questionsmedicales.fr › Eucaryotes › Animaux › Invertébrés › Helminthes › Nematoda › Chromadorea › Strongylida › Trichostrongyloidea › Haemonchus › Synthesis and structure-activity relationship...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Synthesis and structure-activity relationship...
questionsmedicales.fr › Phénomènes chimiques › Structure moléculaire › Synthesis and structure-activity relationship...
questionsmedicales.fr › Phénomènes physiologiques de l'appareil locomoteur et du système nerveux › Phénomènes physiologiques du système locomoteur › Mouvement › Activité motrice › Synthesis and structure-activity relationship...
questionsmedicales.fr › Composés hétérocycliques › Composés hétéromonocycliques › Azoles › Oxazoles › Oxadiazoles › Synthesis and structure-activity relationship...
questionsmedicales.fr › Techniques d'investigation › Évaluation préclinique de médicament › Tests de sensibilité parasitaire › Synthesis and structure-activity relationship...
questionsmedicales.fr › Composés hétérocycliques › Composés hétéromonocycliques › Pyrrolidines › Synthesis and structure-activity relationship...
questionsmedicales.fr › Phénomènes chimiques › Phénomènes de chimie organique › Isomérie › Stéréoisomérie › Synthesis and structure-activity relationship...
questionsmedicales.fr › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Phénomènes pharmacologiques › Relation structure-activité › Synthesis and structure-activity relationship...