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Aromatic or Hetero-aromatic Directly Attached Tri and Tetrasubstituted Methanes: New Chemical Entities as Anti-Infectives.
Curr Med Chem
March 2023
Medicinal & Process Chemistry Division, Gautam Panda, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Lucknow 226031, UP, India.
Tri and Tetra-substituted Methanes (TRSMs) are a significant structural motif in many approved drugs and prodrugs. There is increasing use of TRSM units in medicinal chemistry, and many derivatives are specifically designed to make drug-target interactions through new chemical space around TRSM moiety. In this perspective, we describe synthetic challenges for accessing a range of functionalized selective TRSMs and their molecular mechanism of action, especially as anti-infectives.
View Article and Find Full Text PDFDrug Repurposing Based on Protozoan Proteome: In Vitro Evaluation of In Silico Screened Compounds against .
Pharmaceutics
August 2022
Laboratory of Preclinical Assays and Research of Alternative Sources of Innovative Therapy for Toxoplasmosis and Other Sicknesses (PARASITTOS), Departamento de Morfologia e Patologia Básica, Faculdade de Medicina de Jundiaí, Jundiaí 13202-550, Brazil.
is a protozoan that infects up to a third of the world's population. This parasite can cause serious problems, especially if a woman is infected during pregnancy, when toxoplasmosis can cause miscarriage, or serious complications to the baby, or in an immunocompromised person, when the infection can possibly affect the patient's eyes or brain. To identify potential drug candidates that could counter toxoplasmosis, we selected 13 compounds which were pre-screened in silico based on the proteome of to be evaluated in vitro against the parasite in a cell-based assay.
View Article and Find Full Text PDFRepurposing existing drugs for the treatment of COVID-19/SARS-CoV-2 infection: A review describing drug mechanisms of action.
Biochem Pharmacol
January 2021
Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center School of Medicine, New Orleans, LA, USA; Stanley Scott Cancer Research Center, Louisiana State University Health Sciences Center, New Orleans, LA, USA. Electronic address:
The outbreak of a novel coronavirus (SARS-CoV-2) has caused a major public health concern across the globe. SARS-CoV-2 is the seventh coronavirus that is known to cause human disease. As of September 2020, SARS-CoV-2 has been reported in 213 countries and more than 31 million cases have been confirmed, with an estimated mortality rate of ∼3%.
View Article and Find Full Text PDFAn investigation into the mechanism of action of almitrine on isolated rat diaphragm muscle fatigue.
Respiration
October 2002
Department of Human Anatomy and Physiology, Conway Institute of Biomolecular and Biomedical Research, National University of Ireland, Dublin, Ireland.
Background: Previous studies have shown that almitrine bismesylate, a respiratory stimulant which acts on the mitochondrial electron transport chain, enhances recovery of rat diaphragm muscle from fatigue.
Objectives: Our aim is to investigate if the enhanced recovery is due to an anti-oxidant property of almitrine, since the electron transport chain is a major site of intracellular free radical production.
Methods: A low-frequency fatigue protocol was used (30 Hz; 250 ms; delivered once every 2 s for 5 min), and the effects of almitrine before and after fatigue onset were compared to those of the anti-oxidant compound N-acetylcysteine (NAC).
Effects of the respiratory stimulant almitrine on breathing and FOS expression in the brain of fetal and newborn sheep.
Pediatr Res
April 1999
Department of Physiology, Monash University, Clayton, Victoria, Australia.
Almitrine is a piperazine derivative known to stimulate breathing in the adult but cause apnea in fetal sheep. In fetal sheep (127-133 d gestation; term = 147 d) we confirmed this finding, but found that almitrine (4 mg/kg, i.v.
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