title: Tellurium-based cysteine protease inhibitors: evaluation of novel organotellurium(IV) compounds as inhibitors of human cathepsin B.
abstract: New organotellurium(IV) compounds with specific cysteine protease inhibitory activity were synthesized. Serine and aspartic protease activity were not affected by any of these compounds. All Te(IV) compounds tested exhibited high specific second-order constant for cathepsin B inactivation. Tellurium(IV) compound 6 was the best inhibitor of the series, showing a second-order constant of 36,000 M(-1)s(-1). This value is about 100-fold higher than the second-order rate for cysteine protease inactivation shown by the historic Te(IV) compound AS 101 (1). The inhibition was irreversible and time and concentration dependent; no saturation kinetics were observed, suggesting a direct bimolecular reaction. The results described in this paper show that the new organotellurium(IV) compounds are powerful inhibitors of cathepsin B, constituting promising potential anti-metastatic agents.
authors.affiliation: Instituto de Química, Universidade de São Paulo, Av. Prof. Lineu Prestes, 748 CEP 05508-900, São Paulo, SP, Brazil.
authors.forename: Rodrigo L O R
authors.initials: RL
authors.lastname: Cunha
authors.forename: Miriam E
authors.initials: ME
authors.lastname: Urano
authors.forename: Jair R
authors.initials: JR
authors.lastname: Chagas
authors.forename: Paulo C
authors.initials: PC
authors.lastname: Almeida
authors.forename: Cláudia
authors.initials: C
authors.lastname: Bincoletto
authors.forename: Ivarne L S
authors.initials: IL
authors.lastname: Tersariol
authors.forename: João V
authors.initials: JV
authors.lastname: Comasseto
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis; D002401:Cathepsin B / Q000037:antagonists & inhibitors*; D002470:Cell Survival / Q000187:drug effects; D015853:Cysteine Proteinase Inhibitors / Q000138:chemical synthesis*; D018922:HL-60 Cells; D006801:Humans; D007700:Kinetics; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013691:Tellurium
chemical_list: D000970:Antineoplastic Agents; D015853:Cysteine Proteinase Inhibitors; D009942:Organometallic Compounds; D002401:Cathepsin B; D013691:Tellurium