A5087021225- Vitamin K Research Studies
- Pharmacological Effects of Natural Compounds
- Vitamin C and Antioxidants Research
- Liver physiology and pathology
- Congenital Anomalies and Fetal Surgery
- Biochemical and Molecular Research
- Pediatric Hepatobiliary Diseases and Treatments
- X-ray Diffraction in Crystallography
- Crystallography and molecular interactions
- Synthesis and Biological Evaluation
- ATP Synthase and ATPases Research
- Liver Disease Diagnosis and Treatment
- Microbial Metabolism and Applications
- DNA Repair Mechanisms
- Crystallization and Solubility Studies
- Fluorine in Organic Chemistry
- Microbial Applications in Construction Materials
- Colorectal Cancer Treatments and Studies
- Organ Transplantation Techniques and Outcomes
- Cancer Mechanisms and Therapy
- Computational Drug Discovery Methods
- Chemical Synthesis and Analysis
Stony Brook University
2016-2019
Center for Cancer Research
2019
National Cancer Institute
2019
Target (United States)
2019
National Institutes of Health
2019
Memorial Sloan Kettering Cancer Center
2016
Cornell University
2016
Albert Einstein College of Medicine
2016
Montefiore Medical Center
2016
4-Oxo-4-phenyl-but-2-enoates inhibit MenB, the 1,4-dihydroxyl-2-naphthoyl-CoA synthase in bacterial menaquinone (MK) biosynthesis pathway, through formation of an adduct with coenzyme A (CoA). Here, we show that corresponding methyl butenoates have MIC values as low 0.35-0.75 µg/mL against drug sensitive and resistant strains Staphylococcus aureus. Mode action studies on most potent compound, 4-(4-chlorophenyl)-4-oxobut-2-enoate (1), reveal 1 is converted into CoA S. aureus cells, this binds...
MenE is an o-succinylbenzoyl-CoA (OSB-CoA) synthetase in the bacterial menaquinone biosynthesis pathway and a promising target for development of novel antibacterial agents. The enzyme catalyzes CoA ligation via acyl-adenylate intermediate, we have previously reported tight-binding inhibitors based on stable acyl-sulfonyladenosine analogues this including OSB-AMS (1), which has IC50 value ≤25 nM Escherichia coli MenE. Herein, show that reduces levels Staphylococcus aureus, consistent with...
MicroRNAs (miRNAs) regulate cell fate selection and cellular differentiation. miRNAs of the miR23b polycistron (miR-23b, miR-27b, miR-24) target components TGF-β signaling pathway affect murine bile ductular hepatocyte in vitro. Here we show that miR-23b directly Smad4, which is required for signaling. Injection antagomirs against these into E16.5 fetuses caused increased cytokeratin expression sinusoids primitive elements throughout parenchyma newborn mice. Similar antagomir injection mice...
A stereoselective synthesis has been developed to provide all four side-chain stereoisomers of difluoroindanediol 2, the mixture which was previously identified as an inhibitor o-succinylbenzoate-CoA synthetase MenE in bacterial menaquinone biosynthesis, having promising vitro activity against methicillin-resistant Staphylococcus aureus and Mycobacterium tuberculosis. Only (1R,3S)-diastereomer inhibited biochemical MenE, consistent with computational docking studies, this diastereomer also...
Recent investigations have reported many markers associated with human liver stem/progenitor cells, "oval cells," and identified "niches" in diseased livers where stem cells occur. However, there has remained a need to identify entire lineages of as they differentiate into bile ducts or hepatocytes. We used combined immunohistochemical staining for marker hepatic commitment specification (FOXA2 [Forkhead box A2]), hepatocyte maturation (Albumin HepPar1), features (CK19 [cytokeratin 19])...
N-Acyl sulfamoyladenosines (acyl-AMS) have been used extensively to inhibit adenylate-forming enzymes that are involved in a wide range of biological processes. These acyl-AMS inhibitors nonhydrolyzable mimics the cognate acyl adenylate intermediates bound tightly by enzymes. However, anionic sulfamate moiety presents pharmacological liability may be detrimental cell permeability and pharmacokinetic profiles. We previously developed OSB-AMS (1) as potent inhibitor enzyme MenE, an...
The rise in drug-resistant “superbugs” necessitates the need for novel antimicrobial agents and/or drug targets. Lipoquinones, such as menaquinone (MK), are biologically active electron transporters that play pivotal roles all living organisms. MK is sole carrier transport chain of many deadly human pathogens methicillin-resistant Staphylococcus aureus (MRSA) and Mycobacterium tuberculosis, making biosynthesis pathway an attractive target new development. MenE essential enzyme which...