PXD059717-1

PXD059717 is an original dataset announced via ProteomeXchange.

Title	New derivatives of benzhydroxamic acid with nematocidal activity target nematode specific C2-domain containing protein A0A6F7Q0A8
Description	Parasitic nematodes cause a wide range of diseases in animals, including humans. However, the efficacy of existing anthelmintic drugs, commonly used to treat these infections, is waning due to the increasing prevalence of drug resistance in nematode populations. This growing challenge underscores the urgent need to discover and develop novel nematocidal drugs that target new molecular pathways. In present study, 13 novel derivatives of benzhydroxamic acid (OMKs) were designed and synthesised. Their anthelmintic activity was tested in the nematodes Haemonchus contortus (barber’s pole worm) and Caenorhabditis elegans (elegant worm) and compared with classical anthelmintics. OMKs´ potential toxicity was assessed in mammalian models. Among others, one compound, designated OMK211, showed the most promising results, as it decreased viability and motility of larval and adult stages of both drug-sensitive and drug-resistant strains of H. contortus, and this was not toxic in mammalians cells in vitro and in mice in vivo. Consequently, thermal proteome profiling analysis was used to infer the molecular target of OMK211 in , H. contortus. The results revealed C2-domain containing protein A0A6F7Q0A8, encoded by gene HCON_00184900, as an interacting partner of OMK211. Using advanced structural prediction and docking tools, this protein is considered an interesting molecular target of new nematocidal drugs as its orthologs are present in several nematodes but not in mammals. In conclusion, novel derivatives of benzhydroxamic acid represent a promising new class of potential anthelmintics with a novel mechanism of action
HostingRepository	PRIDE
AnnounceDate	2025-06-16
AnnouncementXML	Submission_2025-06-15_16:21:01.776.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Karel Harant
SpeciesList	scientific name: Haemonchus contortus (Barber pole worm); NCBI TaxID: 6289;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2025-01-13 01:22:09	ID requested
⏵ 1	2025-06-15 16:21:02	announced

Kr, á, tk, ý J, Zaj, í, č, kov, á M, Taki AC, Michel O, Matou, š, kov, á P, Vok, ř, á, l I, Š, t, ě, rbov, á K, Vos, á, la O, Lungerich B, Kurz T, Gasser RB, Harant K, Sk, á, lov, á L, New derivatives of benzhydroxamic acid with nematocidal activity against Haemonchus contortus and Caenorhabditis elegans. Int J Parasitol Drugs Drug Resist, 28():100599(2025) [pubmed]

10.1016/j.ijpddr.2025.100599;

submitter keyword: Nematode, H. contortus

prof. RNDr. Lenka Skálová, Ph.D.
contact affiliation	Department of Biochemical Sciences, Faculty of Pharmacy, Charles University, Hradec Králové, Czech Republic
contact email	lenka.skalova@faf.cuni.cz
lab head
Karel Harant
contact affiliation	Charles University
contact email	harant@natur.cuni.cz
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD059717
     1. Label: PRIDE project
     2. Name: New derivatives of benzhydroxamic acid with nematocidal activity target nematode specific C2-domain containing protein A0A6F7Q0A8