3
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: not found
      • Article: not found

      New anti-inflammatory thiazolyl-carbonyl-thiosemicarbazides and thiazolyl-azoles with antioxidant properties as potential iNOS inhibitors

      Read this article at

      ScienceOpenPublisher
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Related collections

          Most cited references36

          • Record: found
          • Abstract: found
          • Article: found
          Is Open Access

          Acute-phase proteins: As diagnostic tool

          The varied reactions of the host to infection, inflammation, or trauma are collectively known as the acute-phase response and encompass a wide range of pathophysiological responses such as pyrexia, leukocytosis, hormone alterations, and muscle protein depletion combining to minimize tissue damage while enhancing the repair process. The mechanism for stimulation of hepatic production of acute-phase proteins is by proinflammatory cytokines. The functions of positive acute-phase proteins (APP) are regarded as important in optimization and trapping of microorganism and their products, in activating the complement system, in binding cellular remnants like nuclear fractions, in neutralizing enzymes, scavenging free hemoglobin and radicals, and in modulating the host’s immune response. APP can be used as diagnostic tool in many diseases like bovine respiratory syncytial virus, prostate cancer, bronchopneumonia, multiple myeloma, mastitis, Streptococcus suis infection, starvation, or lymphatic neoplasia. Thus, acute-phase proteins may provide an alternative means of monitoring animal health.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Structure-function studies on nitric oxide synthases.

            Nitric oxide synthase (NOS) catalyzes the oxidation of one l-arginine guanidinium N atom to nitric oxide (NO). NOS consists of a heme domain linked to a flavin mononucleotide (FMN)/flavin adenine dinucleotide (FAD) reductase that shuttles electrons from nicotinamide adenine dinucleotide phosphate (NADPH) to the heme. This review summarizes various aspects of NOS structure and function derived from crystal structures coupled with a wealth of biochemical and biophysical data. This includes the binding of diatomic ligands, especially the product, NO, whose binding to the heme iron blocks enzyme activity. An unusual feature of NOS catalysis is the strict requirement for the essential cofactor, tetrahydrobiopterin (H4B). It now is generally agreed that H4B serves as an electron donor to the heme-oxy complex. The reason NOS may have recruited H4B as an electron transfer cofactor is to provide rapid coupled proton/electron transfer required for O2 activation. NOS is a highly regulated enzyme which is controlled by calmodulin (CaM) at the level of electron transfer within the FMN/FAD reductase and between the reductase and heme domains. Recent crystal structures provide a basis for developing models on the structural underpinnings of NOS regulation. In addition to the complex and fascinating functional and regulatory features of NOS, NOS is an important therapeutic target. Crystal structures have revealed the structural basis of isoform-selective inhibition by a group of dipeptide inhibitors which opens the way for structure-based inhibitor design.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Phenethylthiazolethiourea (PETT) compounds, a new class of HIV-1 reverse transcriptase inhibitors. 1. Synthesis and basic structure-activity relationship studies of PETT analogs.

              A novel series of potent specific HIV-1 inhibitory compounds is described. The lead compound in the series, N-(2-phenethyl)-N'-(2-thiazolyl)thiourea (1), inhibits HIV-1 RT using rCdG as the template with an IC50 of 0.9 microM. In MT-4 cells, compound 1 inhibits HIV-1 with an ED50 of 1.3 microM. The 50% cytotoxic dose in cell culture is > 380 microM. The chemical structure-activity relationship (SAR) was developed by notionally dividing the lead compound in four quadrants. The SAR strategy had two phases. The first phase involved optimization of antiviral activity through independent variation of quadrants 1-4. The second phase involved the preparation of hybrid structures combining the best of these substituents. Further SAR studies and pharmacokinetic considerations led to the identification of N-(2-pyridyl)-N'-(5-bromo-2-pyridyl)-thiourea (62; LY300046.HCl) as a candidate for clinical evaluation. LY300046.HCl inhibits HIV-1 RT with an IC50 of 15 nM and in cell culture has an ED50 of 20 nM.
                Bookmark

                Author and article information

                Journal
                Archives of Pharmacal Research
                Arch. Pharm. Res.
                Springer Science and Business Media LLC
                0253-6269
                1976-3786
                June 2013
                March 16 2013
                June 2013
                : 36
                : 6
                : 702-714
                Article
                10.1007/s12272-013-0083-9
                4369cdf0-e664-4bbe-b5d8-5cf1296d4739
                © 2013

                http://www.springer.com/tdm


                Comments

                Comment on this article