<i>In silico</i> and NMR studies on pharmaceutical compounds with therapeutic action against Myasthenia Gravis

Myasthenia Gravis, a chronic autoimmune disease, is primarily treated with acetylcholinesterase inhibitors. However, these drugs are not specific, and their mechanism of action against the disease has not been elucidated. They have a propensity to act on different targets, and their therapeutic action is symptomatic. For this reason, we have studied the interactions of commercially available drugs against Myasthenia Gravis to various enzyme targets to examine if there is any selectivity in their action and possibly to reveal any potential use for other diseases. In particular, the Computational Chemistry programs, AutoDock and Maestro, were used to assess the binding of azathioprine, prednisone, and pyridostigmine to different classes of enzymes, such as: cyclooxygenases (COX-1, COX-2), monoamine oxidases (MAO-A, MAO-B), angiotensin receptors (AT1, AT2), and lipoxygenases (LOX-1, 5-LOX). Molecular Dynamics simulations were employed to further analyze the stability and interactions of the most effective compounds. Using <i>in silico</i> platforms it was found that these drugs are not toxic, they do not produce unwanted adverse eaffects, and that pyridostigmine seems to be the best compound according to the ADME results. Additionally, Saturation Transfer Difference NMR experiments were carried out and confirmed the binding of azathioprine to LOX-5 at both the molecular and atomic levels. The <i>in vitro</i> evaluation of azathioprine and prednisone also revealed important inhibition of human 15-LOX-1 over general lipoxygenase activity. Finally, it was found that these drugs have potential for use in various biological and pharmacological applications such as CNS drugs.