salicylates and Chlamydia-Infections

Topics: Antimetabolites; Arthritis, Reactive; Chlamydia; Chlamydia Infections; Dysentery, Bacillary; Female; Hepatitis B Antigens; Herpesviridae Infections; Humans; Indomethacin; Leukocyte Count; Male; Mycoplasma; Mycoplasma Infections; Phenylbutazone; Prognosis; Salicylates; Salmonella Infections; Sexually Transmitted Diseases; Shigella; Synovial Fluid

A combined application of statistical molecular design (SMD), quantitative structure-activity relationship (QSAR) modeling and prediction of new active compounds was effectively used to develop salicylidene acylhydrazides as inhibitors of type III secretion (T3S) in the Gram-negative pathogen Yersinia pseudotuberculosis. SMD and subsequent synthesis furnished 50 salicylidene acylhydrazides in high purity. Based on data from biological evaluation in T3S linked assays 18 compounds were classified as active and 25 compounds showed a dose-dependent inhibition. The 25 compounds were used to compute two multivariate QSAR models and two multivariate discriminant analysis models were computed from both active and inactive compounds. Three of the models were used to predict 4416 virtual compounds in consensus and eight new compounds were selected as an external test set. Synthesis and biological evaluation of the test set in Y. pseudotuberculosis and the intracellular pathogen Chlamydia trachomatis validated the models. Y. pseudotuberculosis and C. trachomatis cell-based infection models showed that compounds identified in this study are selective and non-toxic inhibitors of T3S dependent virulence.

Topics: Animals; Anti-Bacterial Agents; Cell Line; Chlamydia Infections; Chlamydia trachomatis; Dose-Response Relationship, Drug; Drug Design; HeLa Cells; Humans; Hydrazines; Indicators and Reagents; Mass Spectrometry; Mice; Molecular Conformation; Quantitative Structure-Activity Relationship; Salicylates; Yersinia pseudotuberculosis; Yersinia pseudotuberculosis Infections

Erythema nodosum is the most common and, in its classic form, the most easily recognized cause of inflammatory nodules on the legs. It is characterized by inflammatory, tender, nonulcerating, nonscarring nodules that are typically multiple and bilateral. The rather characteristic clinical presentation can be attributable to one of many causes or associated with a wide spectrum of systemic diseases. Diagnosis, evaluation, and treatment are discussed.

Topics: Adrenal Cortex Hormones; Bacterial Infections; Bed Rest; Behcet Syndrome; Chlamydia Infections; Diagnosis, Differential; Erythema Nodosum; Humans; Mycoses; Prognosis; Salicylates; Sarcoidosis