Abstract
Sepsis is a common and frequently a fatal syndrome. Though, there is steady progress in the management of sepsis, further reduction of its mortality is still hampered by the lack of specific remedies. Recent advances in the understanding of the pathophysiology of sepsis and innovations in drug design have enabled researchers to develop new strategies for the treatment of this complicated condition in a more efficient way. Among these, a variety of small synthetic compounds with the molecular weight lower than 1000Da are emerging rapidly. This review highlights the advances of these small molecules in the treatment of sepsis, which are categorized into the following seven groups according to their pharmaceutical targets: LPS sequestrants and TLR4 antagonists, C5a receptor antagonists, inhibitors of macrophage migration inhibitory factor, inhibitors of QseC signaling, A3 adenosine receptor agonists and A2A adenosine receptor antagonists, estrogen receptor β agonists and caspase inhibitors. Most of the compounds have shown effectiveness in preclinical studies and displayed little or no toxicity. These small molecular compounds are potential candidates for further therapeutic development of sepsis.
Keywords: Sepsis, toll-like receptor 4, C5a receptor, macrophage migration inhibitory factor, QseC signaling, adenosine receptors, estrogen receptor, caspases, fatal syndrome, TLR4 antagonists, C5a receptor antagonists, A3 adenosine receptor agonists, peptidoglycan, gram-positive bacteria, toll-like receptors [TLRs], proinflammatory mediators, tumor necrosis factor a (TNF-a), high-mobility group box 1 (HMGB1), immunosuppression, immunoparalysis, genomics, chemoinformatics, bioinformatics, neutralization, Polymyxin B, pharmacokinetic parameters, complement, septic shock, respiratory distress syndrome, potent chemoattractant, cecal ligation, puncture, chitosan, Rheumatoid Arthritis, Psoriasis, cytokines, glucocorticoids, lethal endotoxemia, Salmonella typhimurium, Francisella tularensis, G-protein-coupled receptors (GPCRs), hypoxia, ischemia, trauma, inflammation, dendritic cells, neutrophils, mast cells, lymphocytes, ESTROGEN RECEPTOR ETA AGONISTS, estradiol, estrogen receptor alpha, gastrointestinal barrier, CASPASE INHIBITORS
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