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The Effects of Synthetic Phosphonates on Living Systems
Published in Richard L. Hilderbrand, The Role of Phosphonates in Living Systems, 2018
The mechanism of action of glyphosate is thought to be associated with the metabolism of aromatic amino acids. Studies by Jaworski125 indicated that phenylalanine biosynthesis was inhibited by glyphosate at the chorismate mutase or prephenate dehydratase steps and that certain aromatic amino acids could reverse those effects. Further studies126 using Escherichia coli indicated that the above enzymes were not affected but that aromatic amino acids would reverse the phytotoxic effect. Exogenous aromatic amino acids supplied to soybean (Glycine Max [L.] Merr. Hill) seedlings reversed the root growth inhibition slightly (10%) but significantly. Glyphosate had no effect on uptake or incorporation of these amino acids and did not substantially affect shikimate dehydrogenase activity in control or amino acid fed seedlings. Duke and Hoagland127 concluded that either the mechanism of action of glyphosate is not the inhibition of aromatic amino acid synthesis or that root fed amino acids are compartmentalized differently than endogenous amino acids. Aromatic amino acids will generally reverse effects of glyphosate on unicellular organisms or on cell cultures of higher plants, but have an equivocal effect in higher plants that are intact. Duke and Hoagland127 suggest that the chelation of divalent metal ion by glyphosate may be important. Ekanayake et al.128 observed effects of glyphosate on amino acid metabolism but did not examine possible mechanisms.
Potential of Mycobacterium tuberculosis chorismate mutase (Rv1885c) as a novel TLR4-mediated adjuvant for dendritic cell-based cancer immunotherapy
Published in OncoImmunology, 2022
Hyein Jeong, So-Young Lee, Hyejun Seo, Dong Hyun Kim, Duhyung Lee, Bum-Joon Kim
Chorismate mutase (CM) plays a central role in the shikimate pathway for the biosynthesis of aromatic amino acids in bacteria, fungi and higher plants, including phenylalanine, tyrosine, and tryptophan, by catalyzing the conversion of chorismate to prephenate.31 There are two putative genes for CM: Rv1885c and Rv0948c. Of these, the secretory form, TBCM (encoded by Rv1885c), is assumed to play a key role in the pathogenesis of tuberculosis,32 and it has low sequence homology among known CM. Therefore, it has gained increased attention as an interesting target for the discovery of antitubercular agents. However, very little is known about the pathogenic role of TBCM in TB pathogenesis. During research regarding its pathogenic role in TB infections, we unexpectedly found that TBCM can induce DC maturation and activation in BMDCs in a TLR4-dependent manner (Figures 1 and 8). Therefore, we hypothesized that TBCM could be effectively used as an immunoadjuvant for DC-based cancer immunotherapy.
Synthesis and evaluation of antimicrobial, antitubercular and anticancer activities of benzimidazole derivatives
Published in Egyptian Journal of Basic and Applied Sciences, 2018
Snehlata Yadav, Balasubramanian Narasimhan, Siong Meng Lim, Kalavathy Ramasamy, Mani Vasudevan, Syed Adnan Ali Shah, Abhishek Mathur
A series of benzimidazole derivatives was synthesized and assessed for its in vitro antimicrobial and anticancer activities. The compounds were also assessed for their in vitro and in vivo antitubercular activity against M. tuberculosis H37Rv. The compounds found to be active in in vivo evaluation in mice models infected with M. tuberculosis were further assessed for their capacity to inhibit the vital mycobacterial enzymes viz., isocitrate lyase, pantothenate synthetase and chorismate mutase. All compounds inhibited these enzymes but to a lesser extent than streptomycin sulphate taken as positive control. Compound 19, the most potent one among the synthesized benzimidazole derivatives exhibited inhibition of 67.56%, 53.45%, and 47.56% against isocitrate lyase, pantothenate synthetase and chorismate mutase, respectively which is comparable to the inhibition of these enzymes by streptomycin sulphate. Most of the synthesized derivatives emerged out as excellent antimicrobial agents as compared to standard antibacterial (cefadroxil) and antifungal (fluconazole) drugs. Compound 10 was found to be the most active antibacterial agent against Gram positive as well as Gram negative bacteria. The results of anticancer activity displayed that majority of the derivatives inhibited the viability of MCF7 cell line, especially; compound 19 was highly potent one among the series (IC50 = 0.0013 µM).
Tetralone derivatives are MIF tautomerase inhibitors and attenuate macrophage activation and amplify the hypothermic response in endotoxemic mice
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2021
János Garai, Marcell Krekó, László Őrfi, Péter Balázs Jakus, Zoltán Rumbus, Patrik Kéringer, András Garami, Eszter Vámos, Dominika Kovács, Viola Bagóné Vántus, Balázs Radnai, Tamás Lóránd
MIF structure shares no homology with other known cytokines. Its structural relatives are the mammalian enzyme, d-dopachrome-tautomerase (DDT)5, and the prokaryotic enzymes: chorismate mutase, 5-carboxymethyl-2-hydroxymuconate-isomerase (CHMI), trans- and cis-3-chloroacrylic acid dehalogenase (CaaD and cis-CaaD, respectively), and 4-oxalocrotonate-tautomerase (4-OT)6,7. MIF exists in a homotrimeric form of 12.4 kD monomers. In each monomer, two α-helices are packed against a four-stranded β-sheet8. There are reports, however, of the occurrence of a dimeric form of MIF9 as well as of other oligomerisation states10 and also of heteromers11.