A5030384400- Cancer therapeutics and mechanisms
- Tuberculosis Research and Epidemiology
- Synthesis and biological activity
- Antibiotics Pharmacokinetics and Efficacy
- Analytical Chemistry and Chromatography
- Drug Transport and Resistance Mechanisms
- Synthesis and Biological Evaluation
- Mosquito-borne diseases and control
- Biochemical Analysis and Sensing Techniques
- Inhalation and Respiratory Drug Delivery
- HIV/AIDS Research and Interventions
- Pharmacogenetics and Drug Metabolism
- Biochemical and Molecular Research
- NF-κB Signaling Pathways
- Infectious Encephalopathies and Encephalitis
- Neurobiology and Insect Physiology Research
- Analytical Methods in Pharmaceuticals
- Phytochemical compounds biological activities
- Vector-borne infectious diseases
- Quinazolinone synthesis and applications
- Insect Pest Control Strategies
- Microfluidic and Capillary Electrophoresis Applications
- Ion Channels and Receptors
- Viral Infections and Vectors
- Sesquiterpenes and Asteraceae Studies
University of Tennessee Health Science Center
2021-2024
National Institute of Pharmaceutical Education and Research
2023-2024
National Institute of Pharmaceutical Education and Research
2016
The lengthy treatment time for tuberculosis (TB) is a primary cause the emergence of multidrug resistant (MDR-TB). One approach to improve TB therapy develop an inhalational that when administered in combination with oral drugs eases and shortens treatment. Spectinamides are new semisynthetic analogues spectinomycin excellent activity against Mycobacterium (Mtb), including MDR XDR Mtb strains. Spectinamide-1599 was chosen as promising candidate development therapy. Using murine model...
Despite decades of research, tuberculosis remains a leading cause death from single infectious agent. Spectinamides are promising novel class antituberculosis agents, and the lead spectinamide 1810 has demonstrated excellent efficacy, safety, drug-like properties in numerous vitro vivo assessments mouse models tuberculosis. In current dose ranging fractionation study, we used 29 different combinations level dosing frequency to characterize exposure-response relationship for model...
Small molecules that interact with the colchicine binding site in tubulin have demonstrated therapeutic efficacy treating cancers. We report design, syntheses, and antitumor efficacies of new analogues pyridopyrimidine hydroquinoxalinone compounds improved drug-like characteristics. Eight analogues, 5j, 5k, 5l, 5m, 5n, 5r, 5t, 5u, showed significant improvement metabolic stability strong antiproliferative potency a panel human cancer cell lines, including melanoma, lung cancer, breast...
Polymerization of tubulin dimers to form microtubules is one the key events in cell proliferation. The inhibition this event has long been recognized as a potential treatment option for various types cancer. Compound 1e was previously developed by our team potent inhibitor polymerization that binds colchicine site. To further improve potency and therapeutic properties compound 1e, we hypothesized based on X-ray crystal structure modification pyrimidine dihydroquinoxalinone scaffold with...
Despite the availability of combined antiretroviral therapy (cART), which reduces HIV replication in chronically HIV-infected patients, associated neurocognitive disorders (HAND) persists brain. The blood-brain barrier (BBB) is major for penetration drugs including antiretrovirals, limiting drug to In present study, we have shown improved brain concentration mice darunavir (DRV), an FDA-approved drug, using intranasal (IN) delivery method that bypasses BBB. Here, compared time-dependent...
Venezuelan and eastern equine encephalitis viruses (VEEV EEEV, respectively) are mosquito-borne, neuroinvasive human pathogens for which no FDA-approved therapeutic exists. Besides the biothreat posed by these when aerosolized, arthropod transmission presents serious health risks to humans, as demonstrated 2019 outbreak of EEE disease in United States that resulted 38 confirmed cases, 19 deaths, neurological effects survivors. Here, we describe discovery a 2-pyrrolidinoquinazolinone...
Abstract ( S )‐Lifitegrast (LFT) is the novel integrin antagonist, approved by Food and drug administration, to treat signs symptoms of dry eye disease. Synthesis racemic LFT, preparative analytical enantiomer separation, chiral interconversion studies are lacking in literature. Hence, our study, synthesis LFT racemate, purification procedure enantiomer, comprehensive advancements focused on rapid enantioselective separation pH‐dependent studies. The racemate employed...
Rationale Amiodarone is reported to cause hepato and pulmonary toxicity in humans, which has been envisaged be due formation of its reactive metabolites, essentially based on structural similarity benzbromarone, a drug withdrawn from the market reasons similar hepatotoxicity. Therefore, purpose this study was detect glutathione conjugates amiodarone diquinone metabolites rat bile using mass spectrometry tools. Methods Wistar rats were dosed orally with an suspension collected via duct...
Microsomal prostaglandin E synthase-1 (mPGES-1) is an inducible enzyme of the cyclooxygenase (COX) cascade that generates E2 (PGE2) during inflammatory conditions. PGE2 known to be a potent immune signaling molecule mediates both peripheral and central inflammations. Inhibition mPGES-1, rather than COX, may overcome cardiovascular side effects associated with long-term COX inhibition by providing more specific strategy target inflammation. However, mPGES-1 inhibitor development hampered...
Spectinamides 1599 and 1810 are lead spectinamide compounds currently under preclinical development to treat multidrug-resistant (MDR) extensively drug-resistant (XDR) tuberculosis. These have previously been tested at various combinations of dose level, dosing frequency, route administration in mouse models Mycobacterium tuberculosis (Mtb) infection healthy animals. Physiologically based pharmacokinetic (PBPK) modeling allows the prediction pharmacokinetics candidate drugs organs/tissues...
Spectinamides are a novel class of narrow-spectrum antitubercular agents with the potential to treat drug-resistant tuberculosis infections. Spectinamide 1810 has shown good safety record following subcutaneous injection in mice or infusion rats but exhibits transient acute toxicity bolus administration either species. To improve therapeutic index 1810, an injectable prodrug strategy was explored. The phosphate 3408 superior maximum tolerated dose compared Gentamicin. Following intravenous...