ABSTRACT
A versatile synthetic route to a novel series of bis-imidazolemethanes designed to inhibit the hCMV protease has been developed and a series of potential metal binding inhibitors has been identified. In selectivity assays, the compounds were highly specific for CMV protease and showed no inhibition (IC50 > 100 microM) of other prototypical serine proteases such as trypsin, elastase, and chymotrypsin. Although the presence of free zinc ions was found to be an absolute requirement for the in vitro biological activity of this class of inhibitor, the potency of the inhibitors could not be improved beyond the micromolar level.
Subject(s)
Imidazoles/chemical synthesis , Serine Endopeptidases/metabolism , Serine Proteinase Inhibitors/chemical synthesis , Chymotrypsin/antagonists & inhibitors , Drug Design , Humans , Imidazoles/chemistry , Metals , Molecular Conformation , Molecular Structure , Pancreatic Elastase/antagonists & inhibitors , Serine Proteinase Inhibitors/chemistry , Serine Proteinase Inhibitors/pharmacology , Structure-Activity Relationship , Trypsin/metabolismSubject(s)
Arthroplasty/adverse effects , Cartilage, Articular/transplantation , Hyperplasia/etiology , Temporomandibular Joint Disorders/surgery , Adult , Arthroplasty/methods , Cartilage, Articular/pathology , Female , Humans , Temporomandibular Joint Disorders/pathology , Transplantation, Autologous/adverse effectsABSTRACT
Biopsy reports of squamous cell carcinoma (SCC) and verrucous carcinoma (VC) were retrospectively evaluated to determine the prevalence of smokeless tobacco (ST) use and to ascertain if any clinical or histologic differences existed when comparing ST users with nonusers. Of the 874 SCC cases, 12 patients (1.4%) were ST users as compared with 7.7% (10 of 129) of the VC patients. The carcinomas in ST users, either SCC or VC, were diagnosed at a later age and were more likely to occur in the buccal mucosa/vestibule area. The SCCs in ST users were more often histologically well differentiated. Because of the anatomic site predilection, it appears probable that ST use is a causative factor in the development of some cases of oral carcinoma.
