Molecular docking and simulation studies of some pyrazolone-based bioactive ligands targeting the NF-κB signaling pathways.

NF-κB has become a predominant regulator responsible for multiple physiological and pathological processes. NF-κB signaling pathway has canonical and non-canonical components which strategize the cancer-related metabolic processes. Non-canonical NF-κB pathways are known to contribute towards the chemoresistance of cancer cells. Consequently, NF-κB can be utilized as a potential therapeutic target for modifying the behaviour of tumor cells. In view of this, we herein report a series of pyrazolone-based bioactive ligands that potentially target NF- κB and, thereby, unveil their anticancer properties. The pharmacological screening of the synthesized compounds were carried out using various virtual screening techniques. The anticancer studies of synthesized pyrazolones showed that APAU exhibited the most potent effect against the MCF-7 cells with an IC50 value of 30 µg/ml. Molecular docking studies revealed that the pyrazolones inhibited cell proliferation by targeting the NFκB signaling pathway. The molecular dynamics simulation studies predicted the stability and flexibility of pyrazolone-based bioactive ligands.

Antiproliferative studies of transition metal chelates of a pyrazolone based hydrazone derivative.

Pyrazolone derivatives play a significant role in the treatment of cancer. The synergic effect which emerges from the combination of pyrazolone moiety with hydrazone functionality was investigated. The objective of this study was to explore the antiproliferative potential of copper(II), cobalt(II), nickel(II) and zinc(II) metal chelates synthesized from pyrazolone based hydrazone derivative. The ligand and the metal chelates were characterized by various spectroscopic and analytical studies. The ligand was characterized by single crystal X-ray diffraction analysis.The results were in line with the spectroscopic methods. The geometry optimization of ligand and metal chelates were performed using density functional theory (DFT). The invitro cytotoxicity of ligand and metal chelates against different cancer cell lines was investigated by MTT assay. The cell-viability experiments showed that copper(II) complex is an efficient cytotoxic agent against HeLa cell line. Moreover, possible inhibition mechanism of synthesized compounds was evaluated in silico against HPV16-E6 receptor.Communicated by Ramaswamy H. Sarma.