New derivatives of benzhydroxamic acid with nematocidal activity against Haemonchus contortus and Caenorhabditis elegans

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11160%2F25%3A10498931" target="_blank" >RIV/00216208:11160/25:10498931 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11310/25:10498931

Result on the web

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=-PFOFaTywO" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=-PFOFaTywO</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.ijpddr.2025.100599" target="_blank" >10.1016/j.ijpddr.2025.100599</a>

Result language

angličtina

Original language name

New derivatives of benzhydroxamic acid with nematocidal activity against Haemonchus contortus and Caenorhabditis elegans

Original language 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 the present study, 13 novel derivatives of benzhydroxamic acid (OMKs) were designed and synthesized. Their anthelmintic activity was tested in the parasitic nematode Haemonchus contortus (barber&apos;s pole worm) and the free-living nematode Caenorhabditis elegans and potential toxicity assessed in mammalian models. Compound OMK211 showed the most promising results. It decreased viability and motility of larval and adult stages of both nematode species and of both drug-sensitive and drug-resistant strains of H. contortus at micromolar concentrations with the highest efficacy in H. contortus adult males (IC50 ~ 1 mu M). Moreover, OMK211 was not toxic in mammalians cells in vitro and in mice in vivo. Consequently, thermal proteome profiling analysis was used to infer the putative molecular target of OMK211 in H. contortus. The results revealed C2-domain containing protein A0A6F7Q0A8, encoded by gene HCON_00184,900, as an interacting partner of OMK211. Using advanced structural prediction and docking tools, this protein is considered an interesting putative 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, which deserve further testing.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30104 - Pharmacology and pharmacy

Project

<a href="/en/project/EH22_008%2F0004607" target="_blank" >EH22_008/0004607: New Technologies for Translational Research in Pharmaceutical Sciences /NETPHARM</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2025

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

International Journal for Parasitology: Drugs and Drug Resistance

ISSN

2211-3207

e-ISSN

2211-3207

Volume of the periodical

28

Issue of the periodical within the volume

August

Country of publishing house

NL - THE KINGDOM OF THE NETHERLANDS

Number of pages

15

Pages from-to

100599

UT code for WoS article

001505154500001

EID of the result in the Scopus database

2-s2.0-105005737725