China
Africa
Explore chapters and articles related to this topic
Endothelial Cell Signaling During Wound Healing
Published in John J. Lemasters, Constance Oliver, Cell Biology of Trauma, 2020
The mechanisms of action of the two inhibitors used here bear some discussion. The tyrphostins competitively bind tyrosine kinases and directly interfere with kinase availability for interaction with substrates.80 The phenolic ring structure of tyrphostins imitates that of tyrosine and has been shown to have very low nonspecific toxicity.80 Modifications of this fundamental structure have resulted in enhanced activity against individual growth factors.80,89,93,94 Although tyrphostins have been shown to inhibit FAK activity,42,95 tyrphostins that specifically target and bind to FAK have not been reported. Herbimycin A is benzoquinonoid ansamycin. Its activity may be due to binding protons from reactive sulfhydryl groups of target kinases and the subsequent covering of an active binding site on the kinase.5,96
Inhibition of Growth Factor Action as an Approach to Cancer Chemotherapy
Published in Robert I. Glazer, Developments in Cancer Chemotherapy, 2019
Herbimycin A was selected by a screen for compounds capable of converting the transformed morphology of Rous sarcoma virus-infected rat kidney cells to the normal morphology.92 These morphological changes are seen at concentrations of 0.1 to 1 μg/mℓ herbimycin A and are reversible on removal of the drug. Examination of autophosphorylation of the p60src kinase in immune precipitates revealed that herbimycin A treatment of cells eliminated this activity.92 This was not a direct effect, because herbimycin A added to pp60src immunoprecipitates from control cells did not inhibit the autophosphorylation of pp60src. Geldanamycin and macbecin, two benzoquinonoid ansamycins structurally related to herbimycin, have a similar inhibitory effect on pp60src-protein kinase activity.95
Rifabutin
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
Similar to rifampicin (see Chapter 126, Rifampicin (Rifampin)), rifabutin (also known as ansamycin LM 427) is a derivative of rifamycin S. The most important property of this drug is that it is more active than rifampicin against Mycobacterium avium complex (MAC) in vitro, against this organism growing in alveolar macrophages, and in experimental animals (O’Brien et al., 1987; Perumal et al., 1987; Saito et al., 1988; Young, 1993a; Young, 1993b). The chemical formula of rifabutin is C46H62N4O11 and its molecular weight is 277.23; its molecular structure is shown in Figure 127.1.
Regioselective approach to colchiceine tropolone ring functionalization at C(9) and C(10) yielding new anticancer hybrid derivatives containing heterocyclic structural motifs
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
Krystian Pyta, Natalia Skrzypczak, Piotr Ruszkowski, Franz Bartl, Piotr Przybylski
In order to demonstrate the utility of C(9)- or C(10)-ether intermediates towards the formation of conjugates, those decorated with alkyne were subjected to Huisgen dipolar cycloaddition of CuAAC type (Figure 3). Alkyne intermediates 3f and 4f were used with benzyl, saccharide, and nucleoside azides as well as with azide congener of the ansamycin antibiotic – geldanamycin to afford triazole-bridged conjugates 5a–f and 6a–f, respectively (Figure 3). Reactions were performed predominantly in THF/methanol, whereas TBA/H2O was a convenient solvent system for the synthesis of hybrids 5f and 6f. In turn, the earlier obtained 3b, 4b, 3j, and 4j ether products were used for assembling conjugates via Heck reactions (Figure 4). Structures of these hybrids were confirmed by NMR, FT-IR, and HR-MS (see Supplemental Material, exemplary 1H-13C HMBC couplings shown in Figure 4S). Irrespectively on the type of group installed at the colchicine scaffold (4-iodobenzyl, 4-vinylbenzyl) the ether-4-vinylbenzyl bridge was formed (products 7 and 8, Figure 4). When ether-allyl reactants were used, the analogous Heck reactions did not yield the expected product and we observed decomposition of 3d and 4d into compound 2.
The intriguing role of Rifaximin in gut barrier chronic inflammation and in the treatment of Crohn’s disease
Published in Expert Opinion on Investigational Drugs, 2018
Loris R. Lopetuso, Marco Napoli, Gianenrico Rizzatti, Antonio Gasbarrini
Interestingly, Rifaximin can modulate the bacterial adhesion to the intestinal mucosa, the inflammatory cytokines release and nuclear factor-κB (NF-κB) expression. As a member of Rifamycins, it belongs to the ansamycins family, which has well established anti-inflammatory and immunosuppressive properties [54]. It is able to reduce bacterial related activation and to modulate the adhesion molecules expression patterns associated with T-cell homing to the intestinal mucosa [55].
Antimicrobial treatment with the fixed-dose antibiotic combination RHB-104 for Mycobacterium avium subspecies paratuberculosis in Crohn’s disease: pharmacological and clinical implications
Published in Expert Opinion on Biological Therapy, 2019
Edoardo Savarino, Lorenzo Bertani, Linda Ceccarelli, Giorgia Bodini, Fabiana Zingone, Andrea Buda, Sonia Facchin, Greta Lorenzon, Santino Marchi, Elisa Marabotto, Nicola De Bortoli, Vincenzo Savarino, Francesco Costa, Corrado Blandizzi
RIF, previously designated as ansamycin or LM 427, is a spiropiperidyl-rifamycin that shares several properties of the rifamycin family members, such as rifampicin and rifapentine [66]. Rifampicin is commonly used for treatment of non-tuberculous mycobacterial infections [49]. Like other rifamycins, it binds prokaryotic DNA-dependent RNA polymerases causing their inhibition [67]. In Mycobacterium spp, RNA polymerase comprises five subunits, and the binding site of rifamycins lies within the β-subunit, which is the catalytic core of this enzyme. As a consequence, acquired resistance to rifamycin – that has been well documented in M. tubercolosis – [68] is conferred primarily by mutations in the rpoB gene, which encodes the β-subunit of RNA polymerase [69], even though a significant proportion of resistant M. avium strains may lack a missense mutation in this gene [70]. Current evidence suggests that a similar clustering of resistance-associated mutations occurs also in other mycobacteria [47,71]. In an interesting Dutch study, which evaluated the effects of various antimicrobial agents on non-tubercular mycobacteria, CLA and RIF were the most active, with 87% and 83% of all isolates, respectively, that were found to be susceptible [72]. In this setting, RIF displayed considerably lower MIC values than CLA for M. avium (MIC ratio 5–10), M. tuberculosis (MIC ratio 2–4) and M. leprae (MIC ratio 10) [72–74]. A recent study estimated a MIC ≤ 0.25–16 µg/ml of RIF for M. avium in clinical isolates [75]. Same results are observed for MAP in an interesting Italian study [76]. Synergistic effects against M. avium, leading to an increase in the permeability of the outer cell envelope, have been observed with combinations of RIF and ethambutol [77]. In addition, studies on patients with HIV and M. avium infection have reported that RIF could protect against the development of CLA resistance [78,79]. For this reason, in lung diseases due to M. avium, RIF is always associated with CLA [49,80].