A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä
Triggering Breast Cancer Apoptosis via Cyclin-Dependent Kinase Inhibition and DNA Damage by Novel Pyrimidinone and 1,2,4-Triazolo[4,3-a]pyrimidinone Derivatives (2024)

Abd Al Moaty, M. N., El Kilany, Y., Awad, L. F., Soliman, S. M., Barakat, A., Ibrahim, N. A., Abu-Serie, M. M., Haukka, M., El-Yazbi, A., & Teleb, M. (2024). Triggering Breast Cancer Apoptosis via Cyclin-Dependent Kinase Inhibition and DNA Damage by Novel Pyrimidinone and 1,2,4-Triazolo[4,3-a]pyrimidinone Derivatives. ACS Omega, Early online. https://doi.org/10.1021/acsomega.4c00466

JYU-tekijät tai -toimittajat

Julkaisun tiedot

Julkaisun kaikki tekijät tai toimittajat: Abd Al Moaty, Mohamed N.; El Kilany, Yeldez; Awad, Laila F.; Soliman, Saied M.; Barakat, Assem; Ibrahim, Nihal A.; Abu-Serie, Marwa M.; Haukka, Matti; El-Yazbi, Amira; Teleb, Mohamed

Lehti tai sarja: ACS Omega

ISSN: 2470-1343

eISSN: 2470-1343

Julkaisuvuosi: 2024

Ilmestymispäivä: 06.05.2024

Volyymi: Early online

Kustantaja: American Chemical Society (ACS)

Julkaisumaa: Yhdysvallat (USA)

Julkaisun kieli: englanti

DOI: https://doi.org/10.1021/acsomega.4c00466

Julkaisun avoin saatavuus: Avoimesti saatavilla

Julkaisukanavan avoin saatavuus: Osittain avoin julkaisukanava

Tiivistelmä

Combinations of apoptotic inducers are common clinical practice in breast cancer. However, their efficacy is limited by the heterogeneous pharmacokinetic profiles. An advantageous alternative is merging their molecular entities in hybrid multitargeted scaffolds exhibiting synergistic activities and uniform distribution. Herein, we report apoptotic inducers simultaneously targeting DNA and CDK-2 (cyclin-dependent kinase-2) inspired by studies revealing that CDK-2 inhibition sensitizes breast cancer to DNA-damaging agents. Accordingly, rationally substituted pyrimidines and triazolopyrimidines were synthesized and assayed by MTT against MCF-7, MDA-MB231, and Wi-38 cells compared to doxorubicin. The N-(4-amino-2-((2-hydrazinyl-2-oxoethyl)thio)-6-oxo-1,6-dihydropyrimidin-5-yl)acetamide 5 and its p-nitrophenylhydrazone 8 were the study hits against MCF-7 (IC50 = 0.050 and 0.146 μM) and MDA-MB231 (IC50 = 0.826 and 0.583 μM), induced DNA damage at 10.64 and 30.03 nM, and inhibited CDK-2 (IC50 = 0.172 and 0.189 μM). 5 induced MCF-7 apoptosis by 46.75% and disrupted cell cycle during S phase. Docking and MD simulations postulated their stable key interactions.

YSO-asiasanat: fluoresenssi; perinnöllisyystiede; seokset; syöpätaudit

Vapaat asiasanat: apoptosis; cancer; fluorescence; genetics; mixtures

Liittyvät organisaatiot

OKM-raportointi: Kyllä

Raportointivuosi: 2024

Alustava JUFO-taso: 1