A5060837722- Drug Transport and Resistance Mechanisms
- HIV/AIDS drug development and treatment
- Synthesis and biological activity
- Hepatitis C virus research
- PARP inhibition in cancer therapy
- Cancer therapeutics and mechanisms
- Pharmacological Effects and Toxicity Studies
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Synthesis and Biological Evaluation
- Computational Drug Discovery Methods
- DNA Repair Mechanisms
- HIV Research and Treatment
- Click Chemistry and Applications
- Pregnancy and Medication Impact
- Microtubule and mitosis dynamics
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Toxin Mechanisms and Immunotoxins
- Biochemical and Molecular Research
- Antimicrobial Resistance in Staphylococcus
- Metal complexes synthesis and properties
- Protein Degradation and Inhibitors
- Integrated Circuits and Semiconductor Failure Analysis
- Inflammatory mediators and NSAID effects
- Hepatitis B Virus Studies
St. John's University
2015-2025
Queens College, CUNY
2022
Rutgers, The State University of New Jersey
2000-2013
Rutgers New Jersey Medical School
2000-2013
National Cancer Institute
2011
Center for Cancer Research
2011
Sun Yat-sen University
2011
Sun Yat-sen University Cancer Center
2011
Universidade Federal do Rio de Janeiro
2008
University of Saskatchewan
2007-2008
Recently, there has been an increasing use of the cyclopropyl ring in drug development to transition candidates from preclinical clinical stage. Important features cyclopropane are, (1) coplanarity three carbon atoms, (2) relatively shorter (1.51 Å) C-C bonds, (3) enhanced π-character and (4) C-H bonds are stronger than those alkanes. The present review will focus on contributions that a makes properties drugs containing it. Consequently, addresses multiple roadblocks can occur during...
DNA death grip Poly(ADP-ribose) polymerase–1 (PARP-1) binds to breaks and recruits repair components. Cancer-killing PARP-1 inhibitor (PARPi) compounds all block the same catalytic site but exhibit vastly different efficacy. Zandarashvili et al. investigated molecular impact of PARPi binding (see Perspective by Slade Eustermann). Different molecules perturb allostery in diverse manners: Some drive promote release from DNA, others retention. These insights help explain efficacies clinic...
Abstract Poly (ADP-ribose) polymerase (PARP) inhibitors elicit antitumour activity in homologous recombination-defective cancers by trapping PARP1 a chromatin-bound state. How cells process trapped remains unclear. Using wild-type and trapping-deficient mutant combined with rapid immunoprecipitation mass spectrometry of endogenous proteins Apex2 proximity labelling, we delineated spectrometry-based interactomes non-trapped PARP1. These analyses identified an interaction between the...
Sildenafil is a potent and selective inhibitor of the type 5 cGMP (cyclic guanosine 3',5'-monophosphate)-specific phosphodiesterase that used clinically to treat erectile dysfunction pulmonary arterial hypertension. Here, we report sildenafil has differential effects on cell surface ABC transporters such as ABCB1, ABCC1, ABCG2 modulate intracompartmental intracellular concentrations chemotherapeutic drugs. In ABCB1-overexpressing cells, nontoxic doses inhibited resistance increased effective...
The use of an acetylene (ethynyl) group in medicinal chemistry coincides with the launch Journal Medicinal Chemistry 1959. Since then, has been broadly exploited drug discovery and development. As a result, it become recognized as privileged structural feature for targeting wide range therapeutic target proteins, including MAO, tyrosine kinases, BACE1, steroid receptors, mGlu5 FFA1/GPR40, HIV-1 RT. Furthermore, terminal alkyne functionality is frequently introduced chemical biology probes...
P-glycoprotein (Pgp, ABCB1) is an ATP-Binding Cassette (ABC) transporter that associated with the development of multidrug resistance in cancer cells. Pgp transports a variety chemically dissimilar amphipathic compounds using energy from ATP hydrolysis. In present study, to elucidate binding sites on for substrates and modulators, we employed site-directed mutagenesis, cell- membrane-based assays, molecular modeling docking. We generated single, double triple mutants substitutions Y307,...
The hepatitis C virus (HCV) NS5B is essential for viral RNA replication and therefore a prime target development of HCV inhibitors. Here, we report the identification new class inhibitors belonging to coumestan family phytoestrogens. Based on in vitro RNA-dependent polymerase (RdRp) inhibition low micromolar range by wedelolactone, naturally occurring coumestan, evaluated anti-NS5B activity four synthetic analogues bearing different patterns substitutions their A D rings, observed good...
The urgent need for novel HCV antiviral agents has provided an impetus understanding the structural requisites of NS5B polymerase inhibitors at molecular level. Toward this objective, comparative field analysis (CoMFA) and similarity indices (CoMSIA) 67 were performed using two methods. First, ligand-based 3D QSAR studies based on lowest energy conformations employing atom fit alignment method. Second, receptor-based models derived from predicted binding obtained by docking all allosteric...
Neratinib, an irreversible inhibitor of epidermal growth factor receptor and human 2, is in phase III clinical trials for patients with 2-positive, locally advanced or metastatic breast cancer. The objective this study was to explore the ability neratinib reverse tumor multidrug resistance attributable overexpression ATP-binding cassette (ABC) transporters. Our results showed that remarkably enhanced sensitivity ABCB1-overexpressing cells ABCB1 substrates. It noteworthy augmented effect...
One of the major causes chemotherapy failure in cancer treatment is multidrug resistance (MDR) which mediated by ABCB1/P-glycoprotein. Previously, through use an extensive screening process, we found that vardenafil, a phosphodiesterase 5 (PDE-5) inhibitor significantly reverses MDR ABCB1 overexpressing cells, and its efficacy was greater than tadalafil, another PDE-5 inhibitor. The present study designed to determine reversal mechanisms vardenafil tadalafil on ABC transporters-mediated MDR....
ATP binding cassette (ABC) transporters, such as P-gp, BCRP and MRP1, can increase efflux of clinical chemotherapeutic agents lead to multi-drug resistance (MDR) in cancer cells. While the discovery development clinically useful inhibitors has proved elusive date, this molecular target nevertheless remains a promising strategy for addressing potentially overcoming MDR. In search new classes inhibitor, we used fluorescent accumulation assays supported by cell flow cytometry MDR reversal...
P-glycoprotein (P-gp) serves as a therapeutic target for the development of multidrug resistance reversal agents. In this study, we synthesized 21 novel compounds by peptide coupling at corresponding carboxyl and amino termini (S)-valine-based bis-thiazole monothiazole derivatives with diverse chemical scaffolds. Using calcein-AM efflux assay, identified compound 28 (IC50 = 1.0 μM) carrying 3,4,5-trimethoxybenzoyl 2-aminobenzophenone groups, respectively, zwitter-ion. Compound inhibited...
ATP-Binding Cassette transporters are involved in the efflux of xenobiotic compounds and responsible for decreasing drug accumulation multidrug resistant (MDR) cells. Discovered by structure-based virtual screening algorithms, bafetinib, a Bcr-Abl/Lyn tyrosine kinase inhibitor, was found to have inhibitory effects on both ABCB1- ABCG2-mediated MDR this in-vitro investigation. Bafetinib significantly sensitized ABCB1 ABCG2 overexpressing cells their anticancer substrates increased...