Development of 1-(4-(Substituted)piperazin-1-yl)-2-((2-((4-methoxybenzyl)thio)pyrimidin-4-yl)oxy)ethanones That Target Poly (ADP-Ribose) Polymerase in Human Breast Cancer Cells

A number of uracil amides cleave poly (ADP-ribose) polymerase and therefore novel thiouracil amide compounds were synthesized and screened for the loss of cell viability in a human-estrogen-receptor-positive breast cancer cell line. The synthesized compounds exhibited moderate to significant efficac...

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Detalles Bibliográficos
Autores principales: Deveshegowda, Suresha N., Metri, Prashant K., Shivakumar, Rashmi, Yang, Ji-Rui, Rangappa, Shobith, Swamynayaka, Ananda, Shanmugam, Muthu K., Nagaraja, Omantheswara, Madegowda, Mahendra, Babu Shubha, Priya, Chinnathambi, Arunachalam, Alharbi, Sulaiman Ali, Pandey, Vijay, Ahn, Kwang Seok, Lobie, Peter E., Basappa, Basappa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9100275/
https://www.ncbi.nlm.nih.gov/pubmed/35566199
http://dx.doi.org/10.3390/molecules27092848
Descripción
Sumario:A number of uracil amides cleave poly (ADP-ribose) polymerase and therefore novel thiouracil amide compounds were synthesized and screened for the loss of cell viability in a human-estrogen-receptor-positive breast cancer cell line. The synthesized compounds exhibited moderate to significant efficacy against human breast cancer cells, where the compound 5e IC(50) value was found to be 18 μM. Thouracil amide compounds 5a and 5e inhibited the catalytical activity of PARP1, enhanced cleavage of PARP1, enhanced phosphorylation of H2AX, and increased CASPASE 3/7 activity. Finally, in silico analysis demonstrated that compound 5e interacted with PARP1. Hence, specific thiouracil amides may serve as new drug-seeds for the development of PARP inhibitors for use in oncology.

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