No abstract

Recent analyses have highlighted the promotion of cancer migration and invasion, mediated through HDAC via MMP-2 and MMP-9. Since both class 1 HDACs and MMP-2/9 are involved in the migration and invasion of cancer, an attempt has been taken to design dual MMP-2/HDAC-8 inhibitors by pharmacophore mapping and molecular docking approaches. The designed molecules were synthesized and showed a range of inhibitory activity against different MMP subtypes. Most of these designed compounds were selective towards MMP-2 but less potent against anti-targets like MMP-8, -12, etc. The highly active MMP-2 inhibitors were also found to be active towards HDAC-8 but less potent against other class 1 HDACs (HDAC-1 and -2). Molecular dynamics simulations revealed that the designed compounds may be acting through a distinct mechanism of action in the 'acetate ion channel' of HDAC-8. Some potent dual MMP-2/HDAC-8 inhibitors were further explored for in vitro cellular assays against human lung carcinoma cell line A549. These analyses revealed that some of these dual inhibitors have considerable anti-migratory and anti-invasive properties. The work may help to obtain some useful dual inhibitors.

No abstract

A new series of 13-pyridinealkyl berberine analogues was synthesized and their DNA binding efficacy studied by employing spectroscopic, calorimetric and molecular modeling techniques.

COR-D possesses significant anti-leukemic activity in U937 and HL-60 cell lines by acting on the mitochondrial apoptotic pathways. Since the necrotic body formation is low after COR-D treatment, the occurrence of inflammation in in vivo systems could be reduced, which represents a positive indication in view of therapeutic application.