Abstract
NO (Nitric oxide) is a signaling molecule and exhibits a plethora of biological activities. Three isoforms of NOS (Nitric Oxide Synthase) are involved in NO production viz. iNOS, eNOS and nNOS. Evidence from research shows that pathological conditions such as arthritis, asthma, cardiovascular dysfunctions, hypertension, neurodegeneration and septic shock arise due to an imperfect control of the NO levels.
NOS inhibitors have emerged as the successful solution for control of NO levels. Most of the research attention and expenditure are focused on the two isoforms, iNOS, and nNOS, due to their involvement in various pathological conditions. Due to its physiological role, eNOS is excluded as a drug target. Despite innumerable NOS inhibitors available, selectivity towards a particular isoform, poses a serious challenge in the design of successful inhibitors. With the help of advancement in the respective fields of synthesis, modeling software, bioassays, molecular biology and the perception of the far reached functions of NO and role of NOS enzyme; successful efforts have been made by various groups of scientists to get more selective, potent and less toxic inhibitors. The present review summarizes in and out of the various approaches used in the designing of non-selective and selective inhibitors in the recent past.
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