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

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

doi:10.3390/molecules27092848

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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

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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

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, …

Molecules (Basel, Switzerland), Vol.27(9), p.2848

29/04/2022

DOI: https://doi.org/10.3390/molecules27092848

PMID: 35566199

Abstract

apoptosis

breast cancer

PARPi

thiouracil amides

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 IC value was found to be 18 μM. Thouracil amide compounds and 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 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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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
Creators - without role: Suresha N Deveshegowda - University of Mysore
Prashant K Metri - University of Mysore
Rashmi Shivakumar - University of Mysore
Ji-Rui Yang - Tsinghua–Berkeley Shenzhen Institute
Shobith Rangappa - Adichunchanagiri Institute for Molecular Medicine, BG Nagara, Nagamangala Taluk, Mandya 571448, India
Ananda Swamynayaka - University of Mysore
Muthu K Shanmugam - National University of Singapore
Omantheswara Nagaraja - University of Mysore
Mahendra Madegowda - University of Mysore
Priya Babu Shubha - University of Mysore
Arunachalam Chinnathambi - King Saud University
Sulaiman Ali Alharbi - King Saud University
Vijay Pandey - Tsinghua–Berkeley Shenzhen Institute
Kwang Seok Ahn - Kyung Hee University
Peter E Lobie - Tsinghua–Berkeley Shenzhen Institute
Basappa Basappa - University of Mysore
Publication Details: Molecules (Basel, Switzerland), Vol.27(9), p.2848
Identifiers: 9950753608331
Academic Unit: King Saud University
Language: English
Resource Type: Journal article