A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä
Activation of p53 signaling and regression of breast and prostate carcinoma cells by spirooxindole-benzimidazole small molecules (2024)

Barakat, A., Alshahrani, S., Al-Majid, A. M., Alamary, A. S., Haukka, M., Abu-Serie, M., Dömling, A., Domingo, L., & Elshaier, Y. A. M.M. (2024). Activation of p53 signaling and regression of breast and prostate carcinoma cells by spirooxindole-benzimidazole small molecules. Frontiers in Pharmacology, 15, Article 1358089. https://doi.org/10.3389/fphar.2024.1358089

JYU-tekijät tai -toimittajat

Julkaisun tiedot

Julkaisun kaikki tekijät tai toimittajat: Barakat, Assem; Alshahrani, Saeed; Al-Majid, Abdullah Mohammed; Alamary, Abdullah Saleh; Haukka, Matti; Abu-Serie, Marwa, M.; Dömling, Alexander; Domingo, Luis, R.; Elshaier, Yaseen A. M. M.

Lehti tai sarja: Frontiers in Pharmacology

eISSN: 1663-9812

Julkaisuvuosi: 2024

Ilmestymispäivä: 08.04.2024

Volyymi: 15

Artikkelinumero: 1358089

Kustantaja: Frontiers Media SA

Julkaisumaa: Sveitsi

Julkaisun kieli: englanti

DOI: https://doi.org/10.3389/fphar.2024.1358089

Julkaisun avoin saatavuus: Avoimesti saatavilla

Julkaisukanavan avoin saatavuus: Kokonaan avoin julkaisukanava

Julkaisu on rinnakkaistallennettu (JYX): https://jyx.jyu.fi/handle/123456789/94821

Julkaisu on rinnakkaistallennettu: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11033320/

Tiivistelmä

This study discusses the synthesis and use of a new library of spirooxindole-benzimidazole compounds as inhibitors of the signal transducer and activator of p53, a protein involved in regulating cell growth and cancer prevention. The text includes the scientific details of the [3 + 2] cycloaddition (32CA) reaction between azomethine ylide 7a and ethylene 3a within the framework of Molecular Electron Density Theory. The mechanism of the 32CA reaction proceeds through a two-stage one-step process, with emphasis on the highly asynchronous transition state structure. The anti-cancer properties of the synthesized compounds, particularly 6a and 6d, were evaluated. The inhibitory effects of these compounds on the growth of tumor cells (MDA-MB 231 and PC-3) were quantified using IC50 values. This study highlights activation of the p53 pathway by compounds 6a and 6d, leading to upregulation of p53 expression and downregulation of cyclin D and NF-kappa B in treated cells. Additionally, we explored the binding affinity of spirooxindole analogs, particularly compound 6d, to MDM2, a protein involved in regulation of p53. The binding mode and position of compound 6d were compared with those of a co-crystallized standard ligand, suggesting its potential as a lead compound for further preclinical research.

YSO-asiasanat: heterosykliset yhdisteet; bioaktiiviset yhdisteet; inhibiittorit; karsinoomat; rintasyöpä; eturauhassyöpä; syöpäsolut; proteiinit; mutaatiot; lääkekemia; farmakologia

Vapaat asiasanat: spirooxindole; benzimidazole; MEDT; p53; MDM2 inhibitors; NF-kappa B; CDK (cyclin-dependent kinase); electron dencity theory; induced apoptosis; mutant p53; inhibitors; participation; localization; exploration; design

Liittyvät organisaatiot

OKM-raportointi: Kyllä

Raportointivuosi: 2024

Alustava JUFO-taso: 1