Background: P-21 activating kinase 4 (PAK4) is implicated in poor prognosis of many human tumors, particularly in triple negative breast cancer (TNBC) progression. Studies have revealed the crucial role of PAK4 in cell proliferation, anchorage-independent growth and cell migration among other hallmarks of cancer. Thus, PAK4 is an attractive target for anti-TNBC drug design and development. In our research, we used in silico methods to investigate the inhibitory potentials of kaempferol against PAK4 as compared with co-crystallized 4T6 and a standard PAK4 inhibitor-KPT-9274. The ligands were docked into the ATP-binding site of the target enzyme and post-docking validations were calculated. Results: In the molecular docking results, kaempferol had higher affinity than the standard KPT-9274. However, the SP and XP docking scores for the co-crystallized 4T6 were the highest. The analyses of the docking poses showed a favorable interaction between kaempferol and the catalytic-important aminoacyl residues, especially GLU396, LEU398 and ASP458 in the ATP-binding site of PAK4 when compared with what was obtained in the 4T6-PAK4 complex. Molecular mechanics based MM-GBSA was used to validate docking results. The free energy calculations revealed that kaempferol may have a favorable biological activity. Furthermore, the druggability of each ligand was assessed using the QikProp module and the SwissADME online tool. Kaempferol possessed a propitious drug-like property when compared to the standard ligands. Conclusions: We, therefore, put forward a logical argument that kaempferol can be further evaluated as a potential PAK4 inhibitor in TNBC.

Introduction: Acycor-plus (ACY) is a single dose combined analgesic and anti-inflammatory drug. Prolonged usage and overdose often lead to gastro-intestinal ulcerations, inflammations and oxidative stress which increases the use of synthetic H2 antagonists such as cimetidine (CMT). Aims: This study was carried out to monitor the antioxidant and inflammatory effects of ethanolic extract of Momordica charantia (MC) in ACY-administered male Balb/c mice. Materials and Methods: Twenty-five mice weighing between 15-20g were equally divided into five groups and received normal saline (Control), 2.5mg/kg ACY alone (ACY), ACY combined with either 50mg/kg cimetidine (CMT) or 100mg/kg and 200mg/kg ethanolic extract of Momordica charantia (MC100 and MC200, respectively). The animals were sacrificed after three days by cervical dislocation and post-mitochondrial fractions of their livers, kidneys, small intestines and colons were used to assess the activities of antioxidant and inflammatory markers. Results: MC100 and MC200 significantly reduced antioxidant markers except catalase (CAT) when compared with ACY while they increased hepatic myeloperoxidase (MPO) and nitric oxide (NO) (p<0.05). Kidney and colonic MPO activities were significantly reduced by MC100. However, MC200 significantly increased renal CAT, superoxide dismutase (SOD) and SOD/(GPx+CAT) ratio with increased oxidative stress. Conclusion: It can be concluded that MC100 had comparable effect with CMT while MC200 might induce renal toxicity. However, further research is needed using other routes of administration.