title: Effects of some antituberculous and anti-leprotic drugs on cathepsins B, H and L.
abstract: The cysteine proteinases like cathepsins B, L and H are main hydrolytic enzymes present in lysosomes and play an important role in intracellular protein degradation. Tuberculosis and leprosy, both are tissue- destructive diseases. Main drugs used in chemotherapy of these diseases may inhibit the main lysosomal cysteine proteinases i.e. cathepsins B, L and H released during tissue destruction and thus prevent the further destruction of tissue by these enzymes. So the aim of this study is to see the effect of antituberculous and antileprotic drugs on these proteolytic enzymes. The effect of commonly used antituberculous and antileprotic drugs was screened on the activities of purified brain lysosomal cysteine proteinases namely cathepsins B [EC 3.4.22.1], L [EC 3.4.22.15] and H [EC 3.4.22.16]. Among the antileprotic drugs, only clofazimine inhibited the enzymic activities whereas dapsone had no effect whatsoever. In antituberculous drugs, rifampicin was the most inhibitory while isoniazid had little inhibitory potency. Streptomycin and pyrazinamide did not effect the activities at all. As regards the mechanism of inhibition, clofazimine and isoniazid inhibited the enzymes in a non-competitive manner with K values of 0.25 mM and 5.0 mM for cathepsin B, 0.071 mM and 0.833 mM for cathepsin L and 1.513 mM and 0.885 mM for cathepsin H, While rifampicin could effect in a competitive manner with K(i) values of 0.03 mM, 0.125 mM and 0.027 mM for cathepsin B, L and H respectively.
authors.affiliation: Department of Chemistry, Kurukshetra University, 136119 Kurukshetra, Haryana.
authors.forename: Ramesh C
authors.initials: RC
authors.lastname: Kamboj
authors.forename: Neera
authors.initials: N
authors.lastname: Raghav
authors.forename: Ashwani
authors.initials: A
authors.lastname: Mittal
authors.forename: Shiwani
authors.initials: S
authors.lastname: Khurana
authors.forename: Rachna
authors.initials: R
authors.lastname: Sadana
authors.forename: Hari
authors.initials: H
authors.lastname: Singh
keywords: Anti-leprotic drugs; Antituberculous drugs; Brain; Cathepsins; Cysteine proteinases; Lysosomes