Recent clinical research evidence has marked TMAO as a biomarker molecule associated with several homeostasis disruptions, such as myocardial infarction, atherosclerosis, secondary hypertension, irritable bowel syndrome, chronic kidney disease, strokes, and heart failure. The priority is to stop the biosynthesis pathway of TMAO through inhibition gut microbial TMA lysate CutC/D. In fact, structure activity relationships (QSAR) provide the ability to predict potent inhibitors. Moreover, develop suicide substrate inhibitors analogues of the microbial TMA lysate CutC. Time- dependent and irreversible inhibition with no toxicity on gut microbial communities are potential therapeutic approach to suppress platelet hyperactivity and prevent any thrombotic stroke associated with cardiovascular disease. Our targets of this study are (1). Synthesis of potent inhibitors that has highly efficacy in vitro and in vivo study with specificity ; (2) Non-lethal effect on gut microbial community; (3) The leading inhibitor works as irreversible non-competitive inhibitor to get high potency and fewer side effects. (4). Our inhibitor possess physic-chemical pharmaceutical properties as necessary for drug effect. (5). The leading compounds do show acceptable pharmacokinetic/ pharmacodynamics properties.

Targeting the trimethylamine oxide biosynthesis pathway: Discovery new novel inhibitors against gut microbial TMA lysate protects against atherosclerosis lesion, MI and stroke

256th National Meeting (2018)

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