1. Para-Aminosalicylic Acid Acts as an Alternative Substrate of Folate ...
Nov 1, 2012 · PAS is assumed to inhibit dihydropteroate synthase (DHPS) in Mycobacterium tuberculosis (M. tuberculosis) by mimicking the substrate, p- ...
Folate biosynthesis is an established anti-infective target, and the antifolate para-aminosalicylic acid (PAS) was one of the first anti-infectives introduced into clinical practice based on target-based drug discovery. Fifty years later, PAS continues ...
2. Evaluation of para-Aminosalicylic Acid as a Substrate of Multiple Solute ...
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para-Aminosalicylic acid (PAS) is a second-line antituberculosis drug that has been used to treat multidrug-resistant and extensively drug-resistant tuberculosis for more than 60 years. Renal secretion and glomerular filtration are the major pathways ...
3. Synthesis of New Fluorine Substituted Heterocyclic Nitrogen Systems ...
The Schiffs base of PAS was cyclized with chloroacetyl chloride and mercaptoacetic acid to give azetidinone 2, thiazolidinone 3, and spiro- ...
Some new fluorine substituted heterocyclic nitrogen systems 2–17 have been synthesized from ring closure reactions of substituted p-amino salicylic acids (PAS). The Schiffs base of PAS was cyclized with chloroacetyl chloride and mercaptoacetic acid to give azetidinone 2, thiazolidinone 3, and spiro-fluoroindolothiazoline-dione 10. However, PAS when reacted directly with 4-fluorobenzoyl chloride and 5-oxazolinone yielded derivatives 4, 5, and 7. Aminomethylation of PAS using formaldehyde and piperidine or piperazine formed N-alkyl and N,N′-dialkyl derivatives (11 and 12 respectively) upon fluorinated benzoylation gave compounds 13 and 14. Similarly, treatment of PAS with thiosemicarbazide 15 and subsequent cyclization with diethyl oxalate yielded the fluorinated heterocycle 17. The structures of the fluorinated heterocyclic systems have been established on the basis of elemental analysis, 1H NMR, 13C NMR, and MS spectral data. Some of the targets exhibited a high inhibition towards Mycobacterium strain with favorable log P values.
4. A combination screening to identify enhancers of para-aminosalicylic ...
Apr 4, 2022 · Scaffolds with potential additive effect with PAS are reported, opening interesting prospects for mechanism of action studies. We also report ...
Para-aminosalicylic acid (PAS) is an antibiotic that was largely used for the multi-therapy of tuberculosis in the twentieth century. To try to overcome the inconvenience of its low efficacy and poor tolerance, we searched for novel chemical entities able to synergize with PAS using a combination screening against growing axenic Mycobacterium tuberculosis. The screening was performed at a sub-inhibitory concentration of PAS on a library of about 100,000 small molecules. Selected hit compounds were analyzed by dose–response and further probed with an intracellular macrophage assay. Scaffolds with potential additive effect with PAS are reported, opening interesting prospects for mechanism of action studies. We also report here evidence of a yet unknown bio-activation mechanism, involving activation of pyrido[1,2-a]pyrimidin-4-one (PP) derivatives through the Rv3087 protein.
5. Synthesis and Characterization of Transition Metal Complexes of Para ...
Therefore, from the IR spectra it is concluded that PAS behaves as bidentate ligand with OO coordination sites and binds to the metal ions through carboxylate O ...
Oriental Journal of Chemistry is a peer reviewed quarterly research journal of pure and applied chemistry. It publishes standard research papers in almost all thrust areas of current chemistry of academic and commercial importance. It provides a platform for rapid publication of quality research papers, reviews and chemistry letters. Oriental Journal of Chemistry is abstracted and indexed in almost all reputed National and International agencies.
6. Methionine antagonizes para-aminosalicylic acid activity via ...
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para -Aminosalicylic acid (PAS) is a second-line anti-tubercular drug that is used for the treatment of drug-resistant tuberculosis (TB). PAS efficacy in the treatment of TB is limited by its lower potency against Mycobacterium tuberculosis relative to many other drugs in the TB treatment arsenal. It is known that intrinsic metabolites, such as para -aminobenzoic acid (PABA) and methionine, antagonize PAS and structurally related anti-folate drugs. While the basis for PABA-mediated antagonism of anti-folates is understood, the mechanism for methionine-based antagonism remains undefined. In the present study, we used both targeted and untargeted approaches to identify factors associated with methionine-mediated antagonism of PAS activity. We found that synthesis of folate precursors as well as a putative amino acid transporter play crucial roles in this process. We also discovered that intracellular biotin confers intrinsic PAS resistance in a methionine-independent manner. Collectively, our results demonstrate that methionine-mediated antagonism of anti-folate drugs occurs through sustained production of folate precursors.
7. Recent Advances in the Synthesis of Polyamine Derivatives and Their ...
The most common methods of synthesis of PA conjugates are acylation of regioselectively protected PAs or their alkylation under the conditions of the Fukuyama ...
Biogenic polyamines (PAs) are involved in the growth and development of normal cells, and their intracellular concentration is stable. The concentration of PAs in cancer cells is significantly increased to promote and sustain their rapid proliferation. Over the years, synthetic PAs, which differ in their structure, have demonstrated high antitumor activity and are involved in clinical trials. The chemical synthesis of PAs and their conjugates require the correct choice of synthetic pathways—methods for constructing conjugates and the orthogonal protection of amino groups. The most common methods of synthesis of PA conjugates are acylation of regioselectively protected PAs or their alkylation under the conditions of the Fukuyama reaction. One of the most promising methods of PA synthesis is the use of a multicomponent Ugi reaction, which allows various PAs to be obtained in high yields. In this review, we describe and analyze various approaches that are used in the synthesis of polyamines and their conjugates.
8. Para-aminosalicylic acid | chemical compound - Britannica
3 days ago · …the two most important being para-aminosalicylic acid (PAS) and isoniazid. ... pharmaceutical. therapeutic substance. Actions. Cite. Share. Give ...
Other articles where para-aminosalicylic acid is discussed: Crohn disease: drugs, including corticosteroids and aminosalicylic acid compounds, are used to treat Crohn disease. The drugs are effective both in treating acute episodes and in suppressing the disease over the long term. Depending on the circumstances, hematinics, vitamins, high-protein diets, and blood transfusions are also used. Surgical resection of the…
9. Determination of critical concentration for drug susceptibility testing of ...
Nov 5, 2022 · Pure PAS powder was synthesized by HanXiang Biotech Co., Ltd. ... give appropriate credit to the original author(s) and the source, provide a ...
Accurate determination of antimicrobial resistance profiles is of great importance to formulate optimal regimens against multidrug-resistant tuberculosis (MDR-TB). Although para-aminosalicylic acid (PAS) has been widely used clinically, the reliable testing methods for PAS susceptibility were not established. Herein, we aimed to establish critical test concentration for PAS on the Mycobacterial Growth Indicator Tube (MGIT) 960 in our laboratory settings. A total of 102 clinical isolates were included in this study, including 82 wild-type and 20 resistotype isolates. Minimum inhibitory concentration (MIC) was determined by MGIT 960. Whole-genome sequencing was used to identify the mutation patterns potentially conferring PAS resistance. Sequence alignment and structure modelling were carried out to analyze potential drug-resistant mechanism of folC mutant. Overall, the Minimum inhibitory concentration (MIC) distribution demonstrated excellent separation between wild-type and resistotype isolates. The wild-type population were all at least 1 dilution below 4 μg/ml, and the resistotype population were no lower than 4 μg/ml, indicating that 4 μg/ml was appropriate critical concentration to separate these two populations. Of 20 mutant isolates, 12 (60.0%) harbored thyA mutations, 2 (10%) had a mutation on upstream of dfrA, and the remaining isolates had folC mutations. Overall, thyA and folC mutations were scattered throughout the whole gene without any one mutation predominating. All mutations within thyA resulted in high-level resistance to PAS (MIC > 32 μg/ml); whereas the MICs of isolates with folC mutations exhibited great diversity, ranged from 4 to > 32 μg/ml, and sequence and structure analysis partially provided the possible reasons for this diversity. We propose 4 μg/ml as tentative critical concentration for MGIT 960. The major mechanism of PAS resistance is mutations within thyA and folC in MTB isolations. The whole-gene deletion of thyA locus confers high-level resistance to PAS. The diversity of many distinct mutations scattered throughout the full-length folC gene challenges the PCR-based mutation analysis for PAS susceptibility.
10. [PDF] Granupas, INN-para-aminosalicylic acid - European Medicines Agency |
GRANUPAS is a gastro-resistant preparation and, therefore, the acid-resistant coating of the granules protects against degradation in the stomach therefore ...
11. Synthesis and Evaluation of New Fluorinated Anti-Tubercular ...
In the present study, fluorinated analogs of some of the most important anti-TB agents such as p-aminosalicylic acid (PAS), thiacetazone and pyrazinamide were ...
: Treatment of tuberculosis (TB) and the discovery of effective new anti-tubercular drugs are among the most urgent priorities in health organizations all over the world. In the present study, fluorinated analogs of some of the most important anti-TB agents such as p-aminosalicylic acid (PAS), thiacetazone and pyrazinamide were synthesized and tested against TB. The fluorinated analog of thiacetazone was 20 times more potent than the parent compound against M.tuberculosis H37-RV, while the fluorinated p-aminosalicylic acid (PAS) was almost three times less potent than PAS. A few other halogenated analogs of thioacetazone were also synthesized and subjected to anti-M.tuberculosis screening tests. The best halogen substituent was found to be fluorine which has the smallest size from one hand and the strongest electronegativity from the other hand among the halogen atoms. Fluorine therefore could be considered as a golden substituent to improve the anti-M.tuberculosis activity of thioacetazone.
12. The mechanistic basis of susceptibility and resistance to the antitubercular ...
tuberculosis co-infections. Chapter 2 shows that PAS is a pro-drug and is converted, via the M. tuberculosis folate biosynthetic pathway, to hydroxy- ...
University of Minnesota Ph.D. dissertation. May 2019. Major: Microbiology, Immunology and Cancer Biology. Advisor: Anthony Baughn. 1 computer file (PDF); xiv 258 pages.
13. Paser (aminosalicylic acid) dosing, indications, interactions, adverse ...
Mechanism of action postulated to be inhibition of folic acid synthesis (but ... Make sure lab personnel and all your doctors know you use this drug.
Medscape - TB dosing for Paser (aminosalicylic acid), frequency-based adverse effects, comprehensive interactions, contraindications, pregnancy & lactation schedules, and cost information.
14. [PDF] p-Aminosalicylate sodium 5.52 g powder for oral solution
May 3, 2012 · increased because PAS-Na causes decreased prothrombin synthesis in the liver. ... Do not take a double dose to make up for a forgotten dose. If ...
15. [PDF] Para aminosalicylic acid in the treatment of manganese toxicity.
Such complex hydrolyzes above pH 5 giving the [CuLH-2]2- species, which precipitates at pH > 7. PAS forms from pH 5 only a [CuL2]2- complex with low water ...
16. Physician Assistant Studies (PAS) | Penn State - University Bulletin
PAS 774 Career Exploration and Synthesis II will be completed by all ... The goal of this elective rotation is to give the student additional medical ...
PAS 701: Applied Human Structure and Function I
17. [PDF] Changes to an Approved NDA or ANDA | FDA
advertising to make it consistent with any labeling change implemented in accordance with § ... intermediates used in the synthesis of such ingredient. The term ...
18. Para-aminosalicylic acid increases the susceptibility to isoniazid in | IDR
Apr 11, 2019 · Background: The purpose of this work was to assess the activity of para-aminosalicylic acid (PAS) in combination with isoniazid (INH) against ...
Para-aminosalicylic acid increases the susceptibility to isoniazid in clinical isolates of Mycobacterium tuberculosis Tingting Zhang,1,2 Guanglu Jiang,1,2 Shu’an Wen,1,2 Fengmin Huo,1,2 Fen Wang,1,2 Hairong Huang,1,2 Yu Pang1,21National Clinical Laboratory on Tuberculosis, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, People’s Republic of China; 2Beijing Key Laboratory on Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, People’s Republic of ChinaBackground: The purpose of this work was to assess the activity of para-aminosalicylic acid (PAS) in combination with isoniazid (INH) against clinical isolates of Mycobacterium tuberculosis (MTB).Materials and methods: A total of 72 MTB isolates with differential in vitro drug susceptibilities were included in this study, comprising 24 pan-susceptible, 24 MDR-TB, and 24 extensively drug-resistant (XDR) isolates. A microplate alamarBlue assay was performed to identify the minimal inhibitory concentrations (MICs) of MTB isolates. Results: The MIC50 of INH was 4 mg/L, and that of PAS was 0.063 mg/L against MTB isolates when single drug used. The combined use of INH and PAS resulted in 16-fold and 8-fold decrease in MIC50 for INH and PAS, respectively. The INH-PAS revealed synergistic activity in 94.4% of the isolates. In addition, there was no significant difference in the FIC index of the INH-PAS combination among individual isolates harboring different susceptibility pattern (P>0.05).Conclusion: The synergy between INH and PAS is demonstrated using non-multidrug-resistant (non-MDR) and MDR-TB strains, which will provide clinicians with useful hints to reuse this combination for treatment of TB patients in clinical practice.Keywords: Mycobacterium tuberculosis, isoniazid, para-aminosalicylic acid, synergy
19. Pask - PAS domain-containing serine/threonine-protein kinase
... synthesis by mediating phosphorylation of GYS1, leading to GYS1 inactivation ... give medical advice. Release 2023_03 | Statistics · © 2002 – 2023 UniProt ...
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