Synthesis, computational and biological studies of alkyltin(IV) N-methyl-N-hydroxyethyl dithiocarbamate complexes.

Methyltin(IV) of butyltin(IV)-N-hydroxyethyl dithiocarbamate complexes, represented as [(CH3)2Sn(L(OH))2] and [(C4H9)2Sn(L(OH))2] respectively were synthesized and characterized using spectroscopic techniques (1H, 13C and 119Sn NMR) and elemental analysis. Both infrared and NMR data showed that, the complexes were formed via two sulphur atoms of the dithiocarbamate group. This mode of coordination was further supported by the DFT calculation, which suggested the formation of a distorted octahedral geometry around the tin atom. The complexes were screened for their antioxidant, cytotoxicity and anti-inflammatory properties. Four different assays including DPPH, nitric oxide, reducing power and hydrogen peroxides were used for the antioxidant studies, while an in vitro anti-inflammatory study was done using albumin denaturation assay. The complexes showed good antioxidant activity, especially in the DPPH assay. Butyltin(IV)-N-hydroxyethyl dithiocarbamate showed better cytotoxicity activity compared to methyltin(IV)-N-hydroxyethyl dithiocarbamate in the selected cell lines, which included KMST-6, Caco-2 and A549 cell lines. The anti-inflammatory activities revealed that the two complexes have useful activities better than diclofenac used as control drug.

Kaempferol as a Potential PAK4 Inhibitor in Triple Negative Breast Cancer: Extra Precision Glide Docking and Free Energy Calculation.

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 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.