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- Title
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.
- Authors
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
- Abstract
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 IC50 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.
- Subjects
POLY ADP ribose; BREAST cancer; THIOURACIL; CHEMICAL synthesis; AMIDES; URACIL; ADP-ribosylation; CANCER cells
- Publication
Molecules, 2022, Vol 27, Issue 9, p2848
- ISSN
1420-3049
- Publication type
Article
- DOI
10.3390/molecules27092848