The Freundlich group is located at Rutgers University in the Department of Pharmacology & Physiology and the Department of Medicine (Division of Infectious Diseases, Center for Emerging & Re-emerging Pathogens). The Freundlich laboratory is positioned at the intersection of computation, chemistry, and biology to understand the pathogenesis of infectious diseases (caused by M. tuberculosis, ESKAPE bacteria, P. falciparum, and the Zika virus) and translate this toward the discovery of novel therapeutic strategies. Innovative computational workflows, based on machine learning methods with or without high-throughput target-based virtual screening, are devised to discover new small molecule chemical tools with efficacy versus a specific pathogen and then evolve the activity, physiochemical, Absorption-Distribution-Metabolism-Excretion-Toxicity, and pharmacokinetic/pharmacodynamic profiles such that in vivo validation is achieved. This validation is relevant to the actual small molecule, potentially enabling its transition to a drug discovery pipeline, as well as its mechanism of action. While medicinal chemistry heuristics are combined with computational methods in the optimization of molecules pertinent to a range of infectious diseases, biological methods in the laboratory contribute to a fundamental understanding of their mechanism of action with regard to M. tuberculosis. Biochemistry, microbiology, and genetics are harnessed to identify the biological target/s of the small molecule. The Freundlich laboratory is a leading proponent of the study of the polypharmacology of small molecule antitubercular agents, which can arise from metabolic transformations within M. tuberculosis and/or the infected host to realize either activation or inactivation of the small molecule. The end results to date have been the discovery and dissemination of a computational suite of tools for the scientific community to leverage in the study of infectious diseases, a growing understanding of the metabolism of small molecule tool compounds and drug discovery entities within M. tuberculosis and the infected host, and the discovery of valuable probes of the M. tuberculosis biosynthesis of fatty acids, peptidoglycan, and folate co-factors. Efforts are ongoing to translate these basic discoveries toward high impact therapies for tuberculosis infection.
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