Cargando…
Development of Piperazine- and Oxazine-Linked Pyrimidines as p65 Subunit Binders of NF–κB in Human Breast Cancer Cells
Nuclear factor kappa B (NF–κB) is a potential therapeutic target in breast cancer. In the current study, a new class of oxazine– and piperazine–linked pyrimidines was developed as inhibitors of NF–κB, overcoming the complexity of the oxazine structure found in nature and enabling synthesis under lab...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10604619/ https://www.ncbi.nlm.nih.gov/pubmed/37893090 http://dx.doi.org/10.3390/biomedicines11102716 |
_version_ | 1785126878045011968 |
---|---|
author | Ravish, Akshay Narasimhachar, Bhanuprakash C. Xi, Zhang Vishwanath, Divakar Mohan, Arunkumar Gaonkar, Santosh L. Chandrashekara, Paduvalahippe Gowdegowda Ahn, Kwang Seok Pandey, Vijay Lobie, Peter E. Basappa, Basappa |
author_facet | Ravish, Akshay Narasimhachar, Bhanuprakash C. Xi, Zhang Vishwanath, Divakar Mohan, Arunkumar Gaonkar, Santosh L. Chandrashekara, Paduvalahippe Gowdegowda Ahn, Kwang Seok Pandey, Vijay Lobie, Peter E. Basappa, Basappa |
author_sort | Ravish, Akshay |
collection | PubMed |
description | Nuclear factor kappa B (NF–κB) is a potential therapeutic target in breast cancer. In the current study, a new class of oxazine– and piperazine–linked pyrimidines was developed as inhibitors of NF–κB, overcoming the complexity of the oxazine structure found in nature and enabling synthesis under laboratory conditions. Among the series of synthesized and tested oxazine–pyrimidine and piperazine–pyrimidine derivatives, compounds 3a and 5b inhibited breast cancer cell (MCF–7) viability with an IC(50) value of 9.17 and 6.29 µM, respectively. In silico docking studies showed that the pyrimidine ring of 3a and the 4–methoxybenzyl thiol group of 5b could strongly bind the p65 subunit of NF–κB, with the binding energies −9.32 and −7.32 kcal mol(−1). Furthermore, compounds 3a and 5b inhibited NF–κB in MCF–7 breast cancer cells. In conclusion, we herein report newer structures that target NF–κB in BC cells. |
format | Online Article Text |
id | pubmed-10604619 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-106046192023-10-28 Development of Piperazine- and Oxazine-Linked Pyrimidines as p65 Subunit Binders of NF–κB in Human Breast Cancer Cells Ravish, Akshay Narasimhachar, Bhanuprakash C. Xi, Zhang Vishwanath, Divakar Mohan, Arunkumar Gaonkar, Santosh L. Chandrashekara, Paduvalahippe Gowdegowda Ahn, Kwang Seok Pandey, Vijay Lobie, Peter E. Basappa, Basappa Biomedicines Article Nuclear factor kappa B (NF–κB) is a potential therapeutic target in breast cancer. In the current study, a new class of oxazine– and piperazine–linked pyrimidines was developed as inhibitors of NF–κB, overcoming the complexity of the oxazine structure found in nature and enabling synthesis under laboratory conditions. Among the series of synthesized and tested oxazine–pyrimidine and piperazine–pyrimidine derivatives, compounds 3a and 5b inhibited breast cancer cell (MCF–7) viability with an IC(50) value of 9.17 and 6.29 µM, respectively. In silico docking studies showed that the pyrimidine ring of 3a and the 4–methoxybenzyl thiol group of 5b could strongly bind the p65 subunit of NF–κB, with the binding energies −9.32 and −7.32 kcal mol(−1). Furthermore, compounds 3a and 5b inhibited NF–κB in MCF–7 breast cancer cells. In conclusion, we herein report newer structures that target NF–κB in BC cells. MDPI 2023-10-06 /pmc/articles/PMC10604619/ /pubmed/37893090 http://dx.doi.org/10.3390/biomedicines11102716 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Ravish, Akshay Narasimhachar, Bhanuprakash C. Xi, Zhang Vishwanath, Divakar Mohan, Arunkumar Gaonkar, Santosh L. Chandrashekara, Paduvalahippe Gowdegowda Ahn, Kwang Seok Pandey, Vijay Lobie, Peter E. Basappa, Basappa Development of Piperazine- and Oxazine-Linked Pyrimidines as p65 Subunit Binders of NF–κB in Human Breast Cancer Cells |
title | Development of Piperazine- and Oxazine-Linked Pyrimidines as p65 Subunit Binders of NF–κB in Human Breast Cancer Cells |
title_full | Development of Piperazine- and Oxazine-Linked Pyrimidines as p65 Subunit Binders of NF–κB in Human Breast Cancer Cells |
title_fullStr | Development of Piperazine- and Oxazine-Linked Pyrimidines as p65 Subunit Binders of NF–κB in Human Breast Cancer Cells |
title_full_unstemmed | Development of Piperazine- and Oxazine-Linked Pyrimidines as p65 Subunit Binders of NF–κB in Human Breast Cancer Cells |
title_short | Development of Piperazine- and Oxazine-Linked Pyrimidines as p65 Subunit Binders of NF–κB in Human Breast Cancer Cells |
title_sort | development of piperazine- and oxazine-linked pyrimidines as p65 subunit binders of nf–κb in human breast cancer cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10604619/ https://www.ncbi.nlm.nih.gov/pubmed/37893090 http://dx.doi.org/10.3390/biomedicines11102716 |
work_keys_str_mv | AT ravishakshay developmentofpiperazineandoxazinelinkedpyrimidinesasp65subunitbindersofnfkbinhumanbreastcancercells AT narasimhacharbhanuprakashc developmentofpiperazineandoxazinelinkedpyrimidinesasp65subunitbindersofnfkbinhumanbreastcancercells AT xizhang developmentofpiperazineandoxazinelinkedpyrimidinesasp65subunitbindersofnfkbinhumanbreastcancercells AT vishwanathdivakar developmentofpiperazineandoxazinelinkedpyrimidinesasp65subunitbindersofnfkbinhumanbreastcancercells AT mohanarunkumar developmentofpiperazineandoxazinelinkedpyrimidinesasp65subunitbindersofnfkbinhumanbreastcancercells AT gaonkarsantoshl developmentofpiperazineandoxazinelinkedpyrimidinesasp65subunitbindersofnfkbinhumanbreastcancercells AT chandrashekarapaduvalahippegowdegowda developmentofpiperazineandoxazinelinkedpyrimidinesasp65subunitbindersofnfkbinhumanbreastcancercells AT ahnkwangseok developmentofpiperazineandoxazinelinkedpyrimidinesasp65subunitbindersofnfkbinhumanbreastcancercells AT pandeyvijay developmentofpiperazineandoxazinelinkedpyrimidinesasp65subunitbindersofnfkbinhumanbreastcancercells AT lobiepetere developmentofpiperazineandoxazinelinkedpyrimidinesasp65subunitbindersofnfkbinhumanbreastcancercells AT basappabasappa developmentofpiperazineandoxazinelinkedpyrimidinesasp65subunitbindersofnfkbinhumanbreastcancercells |