| Cathepsins are lysosomal proteolytic enzymes involved in the breakdown of peptide bonds. Cathepsins are considered to play an important role in the progression and metastasis of cancer. Cathepsins B and K belong to the subfamily of cysteine cathepsins which are involved in the physiological processes such as maintenance of homeostasis of hormones (renin, etc.), remodeling of extracellular matrix and remodeling of bone matrix. Overexpression of cathepsin B and K is observed in the pathological conditions such as inflammation, cancer, arthritis and osteosarcoma. Cathepsin B and cathepsin K are observed to participate in the activation of angiogenic factors and degradation of basal membrane thus allowing the growth and progression of tumor. Several synthetic inhibitors of cathepsin B and K have been developed almost all of which have been associated with certain disadvantages such as poor bioavailability, toxicity or poor selectivity. Thiosemicarbazone cathepsin B and K inhibitors are small molecule compounds which mimic leupeptin, a natural cysteine cathepsin inhibitor, are considered potent and selective cathepsin B and K inhibitors. The main objective of this research is to synthesize phenylthiosemicarbazone protected tripeptide, containing valine, phenylalanine and arginine amino acids, as a potential inhibitor of cathepsin B and cathepsin K. The synthesized compound has been characterized and confirmed by NMR, HRMS and TLC studies. |
