A5035742323- Synthetic Organic Chemistry Methods
- Cyclopropane Reaction Mechanisms
- Synthesis of Organic Compounds
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Hepatitis B Virus Studies
- Oxidative Organic Chemistry Reactions
- HIV/AIDS drug development and treatment
- Catalytic Alkyne Reactions
- Hepatitis C virus research
- Herpesvirus Infections and Treatments
- Phytochemical compounds biological activities
- Carbohydrate Chemistry and Synthesis
- Marine Sponges and Natural Products
- Monoclonal and Polyclonal Antibodies Research
- Cytomegalovirus and herpesvirus research
- Click Chemistry and Applications
- HIV Research and Treatment
- Viral-associated cancers and disorders
- Asymmetric Synthesis and Catalysis
- Axial and Atropisomeric Chirality Synthesis
- Receptor Mechanisms and Signaling
- Phytochemical Studies and Bioactivities
- Fungal Plant Pathogen Control
- Synthesis and biological activity
City University of New York
2016-2025
Brooklyn College
2016-2025
The Graduate Center, CUNY
2014-2024
Weatherford College
2017
Yale University
2009-2012
University of New Haven
2012
Czech Academy of Sciences, Institute of Biotechnology
2010
National Cancer Institute
2010
Boston College
2004-2008
Prostate specific membrane antigen (PSMA) is a membrane-bound glutamate carboxypeptidase overexpressed in many forms of prostate cancer. Our laboratory has recently disclosed class small molecules, called ARM-Ps (antibody-recruiting molecule targeting cancer) that are capable enhancing antibody-mediated immune recognition cancer cells. Interestingly, during the course these studies, we found to exhibit extraordinarily high potencies toward PSMA, compared previously reported inhibitors. Here,...
Prostate cancer is the second leading cause of cancer-related death among American male population, and society in dire need new approaches to treat this disease. Here we report design, synthesis, biological evaluation a class bifunctional small molecules called antibody-recruiting targeting prostate (ARM-Ps) that enhance recognition cells by human immune system. ARM-P derivatives were designed rationally via computational analysis crystallographic data, demonstrate here these materials are...
ABSTRACT Hepatitis B virus (HBV) remains a major human pathogen despite the development of both antiviral drugs and vaccine, in part because current therapies do not suppress HBV replication far enough to eradicate virus. Here, we screened 51 troponoid compounds for their ability RNaseH activity based on activities α-hydroxytropolones against HIV RNaseH, with goal determining whether tropolone pharmacophore may be promising scaffold anti-HBV drug development. Thirteen inhibited best 50%...
α-Hydroxytropolones are a class of molecules with therapeutic potential against several human diseases. However, structure-activity relationship studies on these have been limited due to scarcity efficient synthetic methods access them. It is demonstrated herein that α-hydroxytropolones can be generated through BCl(3)-mediated ring-opening/aromatization/demethylation process 8-oxabicyclo[3.2.1]octenes. Used in conjunction an improved method based established oxidopyrylium dipolar...
α-Hydroxytropolones are promising leads for a diverse range of therapeutic applications. The following review will discuss the biological studies on α-hydroxytropolones and synthetic methods available to access them.
Staphylococcus aureus (S. aureus) is a Gram-positive bacterial pathogen that has emerged as major public health threat. Here we report the cell wall of S. can be covalently re-engineered to contain non-native small molecules. This process makes use endogenous levels enzyme sortase A (SrtA), which ordinarily functions incorporate proteins into wall. Thus, incubation wild-type bacteria with rationally designed SrtA substrates results in covalent incorporation functional molecular handles...
ABSTRACT Herpes simplex virus 1 (HSV-1) and HSV-2 remain major human pathogens despite the development of anti-HSV therapeutics as some first antiviral drugs. Current therapies are incompletely effective frequently drive evolution drug-resistant mutants. We recently determined that certain natural troponoid compounds such β-thujaplicinol readily suppress HSV-1 replication. Here, we screened 26 synthetic α-hydroxytropolones with goals determining a preliminary structure-activity relationship...
Atropisomerism is a stereochemical phenomenon that results from high configurational stability of chiral axes and an important structural element in many functional molecules. Thus, understanding how different features can influence the be consideration for molecular design. Recent studies have demonstrated certain tropone-based are significantly more stable than those related benzenoids, likely result their relatively smaller external bond angles. The following manuscript explores this...
In the presence of ruthenium-based olefin metathesis catalysts and triphenylphosphine, α,β-unsaturated aldehydes can be olefinated with diazoacetates. This ruthenium-catalyzed transformation has been employed in tandem cross-metathesis to convert terminal olefins into 1,3-dienoic esters a single operation.
Chronic hepatitis B virus infection cannot be cured by current therapies, so new treatments are urgently needed. We recently identified novel inhibitors of the ribonuclease H that suppress viral replication in cell culture. Here, we employed immunodeficient FRG KO mice whose livers had been engrafted with primary human hepatocytes to ask whether can vivo. Humanized infected were treated for two weeks #110, an α-hydroxytropolone, and #208, N-hydroxypyridinedione. Hepatitis titers S e antigen...
Methoxytropolones are useful scaffolds for therapeutic development because of their known biological activity and established value in the synthesis α-hydroxytropolones. Upon treatment with triflic acid, a series 3-methoxy-8-oxabicyclo[3.2.1]octa-3,6-dien-2-ones rearrange rapidly cleanly to form methoxytropolones. Interestingly, bicycles that derived from dimethyl acetylenedicarboxylate (R(2) = R(3) CO2Me) instead furans as major product.
The natural product α-hydroxytropolones manicol and β-thujaplicinol inhibit replication of herpes simplex viruses 1 2 (HSV-1 HSV-2, respectively) at nontoxic concentrations. Because these were originally developed as divalent metal-sequestering inhibitors the ribonuclease H activity HIV-1 reverse transcriptase, likely target related HSV proteins nucleotidyltransferase (NTase) superfamily, which share an "RNase H-like" fold. One potential candidate is pUL15, a component viral terminase...
The total syntheses of the antiinflammatory marine sponge metabolites (+)-cacospongionolide B and E are described. pivotal steps in synthetic route include a three-step sequence that couples two main regions natural product, as well generates side chain dihydropyran ring. activity analogues against bee venom phospholipase A2 suggests cacospongionolides have enantiospecific interactions with enzyme may be independent γ-hydroxybutenolide moiety.
Cryptococcus neoformans is a pathogen that common in immunosuppressed patients. It can be treated with amphotericin B and fluconazole, but the mortality rate remains 15 to 30%. Thus, novel more effective anticryptococcal therapies are needed. The troponoids based on natural products isolated from western red cedar, have broad range of antimicrobial activities. Extracts cedar inhibit growth several fungal species, neither extracts nor troponoid derivatives been tested against C. We screened...
The herpes simplex virus (HSV) type I alkaline nuclease, UL12, has 5'-to-3' exonuclease activity and shares homology with nucleases from other members of the Herpesviridae family. We previously reported that a UL12-null exhibits severe defect in viral growth. To determine whether growth was result loss nuclease or another function we introduced an exonuclease-inactivating mutation into genome. recombinant virus, UL12 D340E (the mutant), behaved identically to null (AN-1) yield experiments,...
Many dsDNA viruses encode DNA-packaging terminases, each containing a nuclease domain that resolves concatemeric DNA into genome-length units. Terminase nucleases resemble the RNase H-superfamily nucleotidyltransferases in folds, and share two-metal-ion catalytic mechanism. Here we show residue K428 of bacteriophage terminase gp2 mediates binding metal cofactor Mg(2+). A K428A mutation allows visualization, at high resolution, ion mode with coupled-octahedral configuration active site,...
A new 3,7-dihydroxytropolone synthetic strategy provides access to a proposed natural product precursor and potent antiviral compounds.
Novel antibiotics are urgently needed. The troponoids [tropones, tropolones, and α-hydroxytropolones (α-HT)] can have anti-bacterial activity. We synthesized or purchased 92 evaluated their antibacterial activities against Staphylococcus aureus, Escherichia coli, Acinetobacter baumannii, Pseudomonas aeruginosa. Preliminary hits were assessed for minimum inhibitory concentrations (MIC80) cytotoxicity (CC50) human hepatoma cells. Sixteen inhibited S. aureus/E. coli/A. baumannii growth by ≥80%...
α-Hydroxy-γ-pyrone-based oxidopyrylium cycloaddition reactions are useful methods for accessing a highly diverse range of oxabicyclo[3.2.1]octane products. Intermolecular variants the reaction require formation methyl triflate-based pre-ylide salt that upon treatment with base in presence alkenes or alkynes leads to α-methoxyenone-containing bicyclic Herein, we describe our discovery use ethanol-stabilized chloroform as solvent generation α-ethoxyenone-containing byproducts. This...