Second-generation piperazine derivatives as promising radiation countermeasures

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11150%2F24%3A10483897" target="_blank" >RIV/00216208:11150/24:10483897 - isvavai.cz</a>

Alternative codes found

RIV/60162694:G44__/25:00563516 RIV/00179906:_____/24:10483897

Result on the web

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=gL1Cf2d3px" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=gL1Cf2d3px</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1039/d4md00311j" target="_blank" >10.1039/d4md00311j</a>

Result language

angličtina

Original language name

Second-generation piperazine derivatives as promising radiation countermeasures

Original language description

The increasing threat of nuclear incidents and the widespread use of ionizing radiation (IR) in medical treatments underscore the urgent need for effective radiation countermeasures. Despite the availability of compounds such as amifostine, their clinical utility is significantly limited by adverse side effects and logistical challenges in administration. This study focuses on the synthesis and evaluation of novel piperazine derivatives as potential radioprotective agents, with the aim of overcoming the limitations associated with current countermeasures. We designed, synthesized, and evaluated a series of 1-(2-hydroxyethyl)piperazine derivatives. The compounds were assessed for cytotoxicity across a panel of human cell lines, and for their radioprotective effects in the MOLT-4 lymphoblastic leukemia cell line and in peripheral blood mononuclear cells (PBMCs) exposed to gamma radiation. The radioprotective efficacy was further quantified using the dicentric chromosome assay (DCA) to measure DNA damage mitigation. Among the synthesized derivatives, compound 6 demonstrated the most significant radioprotective effects in vitro, with minimal cytotoxicity across the tested cell lines. Compound 3 also showed notable efficacy, particularly in reducing dicentric chromosomes, thus indicating its potential to mitigate DNA damage from IR. Both compounds exhibited superior safety profiles and effectiveness compared to amifostine, suggesting their potential as more viable radioprotective agents. This study highlights the development of novel piperazine derivatives with promising radioprotective properties. Compound 6 emerged as the leading candidate, offering an optimal balance between efficacy and safety, with compound 3 also displaying significant potential. These findings support the further development and clinical evaluation of these compounds as safer, and more effective radiation countermeasures.

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

30100 - Basic medicine

Project

<a href="/en/project/NU23-08-00256" target="_blank" >NU23-08-00256: Hit-to-lead development of small molecules for enhanced medical radiation protection</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2024

Confidentiality

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

Name of the periodical

RSC Medicinal Chemistry

ISSN

2632-8682

e-ISSN

2632-8682

Volume of the periodical

15

Issue of the periodical within the volume

8

Country of publishing house

GB - UNITED KINGDOM

Number of pages

12

Pages from-to

2855-2866

UT code for WoS article

001274024700001

EID of the result in the Scopus database

2-s2.0-85199507538