TY - JOUR
T1 - Discovery of Piperazin-2-yl-pyrimidines as Anticancer Agents via Targeting JNK Signaling Pathway in Human MCF-7 Breast Carcinoma
AU - Shivakumar, Rashmi
AU - Sethi, Gautam
AU - Manikanta, Kurnegala
AU - Xi, Zhang
AU - Ravish, Akshay
AU - Uppar, Pradeep M.
AU - Deveshegowda, Suresha N.
AU - Kumar, Arun M.
AU - Basappa, Shreeja
AU - Bhol, Chandra Sekhar
AU - Gaonkar, Santosh L.
AU - Kemparaju, Kempaiah
AU - Chinnathambi, Arunachalam
AU - Alharbi, Sulaiman Ali
AU - Lobie, Peter E.
AU - Pandey, Vijay
AU - Basappa, Basappa
N1 - Publisher Copyright:
© 2024 Wiley-VCH GmbH.
PY - 2024/7/18
Y1 - 2024/7/18
N2 - Breast cancer (BC) is the second leading cause of cancer-related mortality in women, and targeting biological pathways such as the JNK pathway has proven to be a viable therapeutic target for BC therapy. Here, we synthesized piperazin-2-yl-pyrimidines and evaluated them for anticancer activity against MCF-7 cells. In addition, antioxidant, reactive oxygen species (ROS) inhibition, caspase activity, and toxicity in platelets were studied in the presence and absence of active compound IA-6 or IA-7. Our detailed experimental analysis found that the compound IA-7 showed anticancer activity by either activating p-JNK or by inducing radical species in cancer and thrombosis model. Evident to in vitro analysis, the structure based molecular interaction studies of binding of IA-7 to JNK3S exhibited a significant binding energy of −7.56 kcal/mol which was found to be a better binder when compared to previously reported JNK inducer (PC-12). Overall, we herein report the analytically pure IA-7 as lead structure that could be used as a template to develop target based anticancer agents where JNK modulation is predominant.
AB - Breast cancer (BC) is the second leading cause of cancer-related mortality in women, and targeting biological pathways such as the JNK pathway has proven to be a viable therapeutic target for BC therapy. Here, we synthesized piperazin-2-yl-pyrimidines and evaluated them for anticancer activity against MCF-7 cells. In addition, antioxidant, reactive oxygen species (ROS) inhibition, caspase activity, and toxicity in platelets were studied in the presence and absence of active compound IA-6 or IA-7. Our detailed experimental analysis found that the compound IA-7 showed anticancer activity by either activating p-JNK or by inducing radical species in cancer and thrombosis model. Evident to in vitro analysis, the structure based molecular interaction studies of binding of IA-7 to JNK3S exhibited a significant binding energy of −7.56 kcal/mol which was found to be a better binder when compared to previously reported JNK inducer (PC-12). Overall, we herein report the analytically pure IA-7 as lead structure that could be used as a template to develop target based anticancer agents where JNK modulation is predominant.
UR - https://www.scopus.com/pages/publications/85198718753
UR - https://www.scopus.com/pages/publications/85198718753#tab=citedBy
U2 - 10.1002/slct.202400307
DO - 10.1002/slct.202400307
M3 - Article
AN - SCOPUS:85198718753
SN - 2365-6549
VL - 9
JO - ChemistrySelect
JF - ChemistrySelect
IS - 27
M1 - e202400307
ER -
