Synthesis of novel inhibitors of human IMP dehydrogenase is described. These inhibitors are isosteric methylenebis(sulfonamide) analogues 5-8 of earlier reported mycophenolic adenine methylenebis(phosphonate)s 1-3. The parent bis(phosphonate) 1 and its bis(sulfonamide) analogue 5 showed similar sub-micromolar inhibitory activity against IMPDH2 (K(i) approximately 0.2 microM). However, the bis(sulfonamide) analogues 6 and 8 substituted at the position 2 of adenine were approximately 3- to 10-fold less potent inhibitors of IMPDH2 (K(i)=0.3-0.4 microM) than the corresponding parent bis(phosphonate)s 2 and 3 (K(i)=0.04-0.11 microM), respectively.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bmc.2008.06.003 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Effects of Inosine-5'-monophosphate Dehydrogenase (IMPDH/GuaB) Inhibitors on Growth in Standard and Modified Culture Conditions.
Microorganisms
October 2024
Laboratory of Medical Zoology, Department of Microbiology, University of Massachusetts, Amherst, MA 01003, USA.
's inosine-5'-monophosphate dehydrogenase (IMPDH, GuaB encoded by the gene) is a potential therapeutic target. GuaB is necessary for replication in mammalian hosts but not in standard laboratory culture conditions. Therefore, we cannot test novel GuaB inhibitors against without utilizing mammalian infection models.
View Article and Find Full Text PDFHeart transplantation and human immunodeficiency virus-navigating drug-drug interactions: a case report.
AIDS Res Ther
August 2023
Department of Medicine, Division of Infectious Diseases, University of North Carolina School of Medicine, Chapel Hill, USA.
Background: Antiretroviral therapy (ART) has led to a decline in human immunodeficiency virus (HIV)-related mortality, but comorbidities, including organ dysfunction, are increasingly the focus of care. Heart transplant (HT) is a very effective therapeutic strategy for end-stage heart failure (HF); however, clinicians may be hesitant due to concerns of complex drug-drug interactions (DDIs) between ART and HT immunosuppressive regimens and the potential impact of ART on long-term HT outcomes. In this report, we describe long-term (76-month) follow-up of a patient with HIV-positive status who underwent orthotopic HT with special emphasis on complex drug interactions.
View Article and Find Full Text PDFChronic granulomatous disease is an inborn error of immunity due to disrupted function of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex. This results in impaired respiratory burst of phagocytes and insufficient killing of bacteria and fungi. Patients with chronic granulomatous disease are at increased risk for infections, autoinflammation and autoimmunity.
View Article and Find Full Text PDFSafety and efficacy of the mRNA BNT162b2 vaccine against SARS-CoV-2 in five groups of immunocompromised patients and healthy controls in a prospective open-label clinical trial.
EBioMedicine
December 2021
Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden; Department of Medicine Huddinge, Infectious Diseases, Karolinska Institutet, Stockholm, Sweden. Electronic address:
Background: Patients with immunocompromised disorders have mainly been excluded from clinical trials of vaccination against COVID-19. Thus, the aim of this prospective clinical trial was to investigate safety and efficacy of BNT162b2 mRNA vaccination in five selected groups of immunocompromised patients and healthy controls.
Methods: 539 study subjects (449 patients and 90 controls) were included.
Pharmacodynamic assessment of mycophenolic acid in resting and activated target cell population during the first year after renal transplantation.
Br J Clin Pharmacol
June 2020
Department of Pharmacology, Oslo University Hospital, Oslo, Norway.
Aims: To explore the pharmacodynamics of mycophenolic acid (MPA) through inosine monophosphate dehydrogenase (IMPDH) capacity measurement and purine levels in peripheral blood mononuclear cells (PBMC) longitudinally during the first year after renal transplantation (TX).
Methods: PBMC were isolated from renal recipients 0-4 days prior to and 6-9 days, 5-7 weeks and 1 year after TX (before and 1.5 hours after dose).
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!