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
oleh: Suresha N. Deveshegowda, Prashant K. Metri, Rashmi Shivakumar, Ji-Rui Yang, Shobith Rangappa, Ananda Swamynayaka, Muthu K. Shanmugam, Omantheswara Nagaraja, Mahendra Madegowda, Priya Babu Shubha, Arunachalam Chinnathambi, Sulaiman Ali Alharbi, Vijay Pandey, Kwang Seok Ahn, Peter E. Lobie, Basappa Basappa
| Format: | Article |
|---|---|
| Diterbitkan: | MDPI AG 2022-04-01 |
Deskripsi
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 <b>5e</b> IC<sub>50</sub> value was found to be 18 μM. Thouracil amide compounds <b>5a</b> and <b>5e</b> 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 <b>5e</b> interacted with PARP1. Hence, specific thiouracil amides may serve as new drug-seeds for the development of PARP inhibitors for use in oncology.