A comparative account of sar studies of semicarbazones and thiosemicarbazones on cathepsins H and L

Abstract

Cathepsins H and L, lysosomal cysteine proteases have been found in elevated levels in tumor invasion, metastasis, inflammation, atherosclerosis, and various other tissue degenerative diseases. In the past decade, work has largely been focused on evaluation of some non-peptidyl inhibitors of cathepsins as these have been considered as viable drug targets for major diseases. Semicarbazones and thiosemicarbazones, carbonyl derivatives are extensively studied for wide variety of biological activities such as anticonvulsant, anticancer, anti-inflammatory, antihypertensive, antimicrobial, and antiparasitic. These derivatives have also shown to possess parasiticidal activity against Plasmodium falciparum, Plasmodium berghei, Trypanosoma cruzi, Trypanosoma brucei rhodesiense and Toxoplasma gondii. With this background, the present work involved the inhibition and kinetic studies of substituted semicarbazones and thiosemicarbazones on cathepsin H and L. A comparative account of structure–activity relationship for inhibition exerted by synthesized semicarbazones and thiosemicarbazones with varied functional moieties on cathepsins H and L is presented.