A5021173615- Protein Kinase Regulation and GTPase Signaling
- Cancer-related Molecular Pathways
- Mechanisms of cancer metastasis
- Cancer Mechanisms and Therapy
- Crystallization and Solubility Studies
- Cell death mechanisms and regulation
- Amino Acid Enzymes and Metabolism
- Metal complexes synthesis and properties
- Microtubule and mitosis dynamics
- HER2/EGFR in Cancer Research
- X-ray Diffraction in Crystallography
- Steroid Chemistry and Biochemistry
- Coordination Chemistry and Organometallics
- Synthesis and Catalytic Reactions
- Pancreatic function and diabetes
- bioluminescence and chemiluminescence research
- Innovative Microfluidic and Catalytic Techniques Innovation
- Peptidase Inhibition and Analysis
- Chemical Reaction Mechanisms
- Computational Drug Discovery Methods
- Pharmacogenetics and Drug Metabolism
- Organic Chemistry Cycloaddition Reactions
- 14-3-3 protein interactions
- Advanced Breast Cancer Therapies
- Cell Adhesion Molecules Research
University of Puerto Rico System
2007-2025
University of Puerto Rico, Medical Sciences Campus
2015-2024
Scripps Research Institute
1996-1997
Louisiana State University
1996
Vrije Universiteit Amsterdam
1991-1993
The Rho GTPase Rac regulates actin cytoskeleton reorganization to form cell surface extensions (lamellipodia) required for migration/invasion during cancer metastasis. hyperactivation and overexpression are associated with aggressive cancers; thus, interference of the interaction its direct upstream activators, guanine nucleotide exchange factors (GEFs), is a viable strategy inhibiting activity. We synthesized EHop-016, novel inhibitor activity, based on structure established Rac/Rac GEF...
All of the selectivity criteria for catalytic asymmetric aminohydroxylation with sulfonamides “Eq. (a)” are improved when original nitrogen source, Chloramine-T, is replaced by its methyl analogue, Chloramine-M (1). This newly introduced reagent exhibits substantially higher ligand dependence, and most substrates desirable phenomenon ligand-accelerated catalysis was observed. DHQ-H = dihydroquinine, PHAL 1,3-phthalazinediyl.
The Rho GTPases Rac (Ras-related C3 botulinum toxin substrate) and Cdc42 (cell division control protein 42 homolog) regulate cell functions governing cancer malignancy, including polarity, migration, cell-cycle progression. Accordingly, our recently developed inhibitor EHop-016 (IC50, 1,100 nmol/L) inhibits migration viability reduces tumor growth, metastasis, angiogenesis in vivo Herein, we describe MBQ-167, which with IC50 values of 103 78 nmol/L, respectively, metastatic breast cells....
Metastatic disease still lacks effective treatments, and remains the primary cause of cancer mortality. Therefore, there is a critical need to develop better strategies inhibit metastatic cancer. The Rho family GTPase Rac an ideal target for anti-metastatic therapy, because key molecular switch that activated by myriad cell surface receptors promote migration/invasion survival. Previously, we reported design development EHop-016, small molecule compound, which inhibits activity cells with...
Nitrofurfural is a key building block for the synthesis of antimicrobial nitrofurans as active pharmaceutical ingredients. Its involves nitration furfural, substrate derived from biobased resources. However, furfural has delicate heteroaromatic backbone. Typical nitrations involve harsh reaction conditions, which often compromise this structure, resulting in poor reproducibility and low yields. Although acetyl nitrate, mild nitrating agent, suitable task, major deterrents remain. First, its...
Abstract The small G-protein Rac1 is a central player in cancer progression and metastatic dissemination. has been established as bona fide effector of receptor tyrosine kinases, acting signaling node for motility, invasiveness, mitogenesis, gene expression. Previous studies demonstrated that hyperactivated aggressive cellular models prostate cancer. Here, we show CRISPR/Cas9-based knockout leads to impaired cell proliferation migration. Rac1-null cells display profound alterations...
Nitrofurfural is a key building block for the synthesis of antimicrobial nitrofurans as active pharmaceutical ingredients. Its involves nitration furfural, substrate derived from biobased resources. However, furfural has delicate heteroaromatic backbone. Typical nitrations involve harsh reaction conditions, which often compromise this structure, resulting in poor reproducibility and low yields. Although acetyl nitrate, mild nitrating agent, suitable task, major deterrents remain. First, its...
Nitrofurfural is a key building block for the synthesis of antimicrobial nitrofurans as active pharmaceutical ingredients. Its involves nitration furfural, substrate derived from biobased resources. However, furfural has delicate heteroaromatic backbone. Typical nitrations involve harsh reaction conditions, which often compromise this structure, resulting in poor reproducibility and low yields. Although acetyl nitrate, mild nitrating agent, suitable task, major deterrents remain. First, its...
An acquired somatic mutation at codon 816 in the KIT receptor tyrosine kinase is associated with poor prognosis patients systemic mastocytosis and acute myeloid leukemia (AML). Treatment of leukemic cells bearing this an allosteric inhibitor p21-activated (Pak) or its genetic inactivation results growth repression due to enhanced apoptosis. Inhibition upstream effector Rac abrogates oncogene-induced activity Pak. Although both Rac1 Rac2 are constitutively activated via guanine nucleotide...
Triple-negative breast cancer (TNBC) is an aggressive form of cancer, with a high predisposition for locally invasive and metastatic cancer. With the objective to reduce metastasis, we developed small molecule inhibitors target drivers Rho GTPases Rac Cdc42. Of these, MBQ-167 inhibits both Cdc42 IC50s 103 78 nmol/L, respectively; consequently, p21-activated kinase (PAK) signaling, cell proliferation, migration, mammosphere growth; induces cell-cycle arrest apoptosis; decreases HER2-type...
The solubility of modafinil (MOD) form I, an antinarcoleptic drug, was measured at temperatures ranging from 278.15 to 333.15 K in ten neat solvents (acetone, acetonitrile, dimethylformamide, ethanol, ethyl acetate, methanol, methylethylketone, 1-propanol, 2-propanol, and water) two binary solvent mixtures (acetone + water methanol water). results employing the polythermal method demonstrate that increases with increasing temperature constant composition mixtures. Moreover, MOD decreases...
Intensified production of smart drug modafinil under continuous flow and sustainable conditions.
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of Phosphonate and Thiophosphonate Esters Amides from Hydrogen-Phosphinates by a Novel One-Pot Activation-Coupling-Oxidation ProcedureMaria de Fatima Fernandez, Cornelis P. Vlaar, Hong Fan, Yen-Hsiang Liu, Frank R. Fronczek, Robert HammerCite this: J. Org. Chem. 1995, 60, 23, 7390–7391Publication Date (Print):November 1, 1995Publication History Published online1 May 2002Published inissue 1 November...
The Rho GTPases Rac and Cdc42 are potential targets against metastatic diseases. We characterized the small molecule MBQ-167 as an effective dual Rac/Cdc42 inhibitor that reduces HER2-type tumor growth metastasis in mice by ∼90%. This study reports pharmacokinetics tissue distribution of following intraperitoneal oral single-dose administrations. first developed validated a bioanalytical method for quantitation mouse plasma tissues supercritical fluid chromatography coupled with electrospray...
Rac and Cdc42, are homologous GTPases that regulate cell migration, invasion, cycle progression; thus, representing key targets for metastasis therapy. We previously reported on the efficacy of MBQ-167, which blocks both Rac1 Cdc42 in breast cancer cells mouse models metastasis. To identify compounds with increased activity, a panel MBQ-167 derivatives was synthesized, maintaining its 9-ethyl-3-(1H-1,2,3-triazol-1-yl)-9H-carbazole core. Similar to MBQ-168 EHop-097, inhibit activation Rac1B...
Trastuzumab and trastuzumab-based treatments are the standard of care for breast cancer patients who overexpress human epidermal growth factor receptor 2 (HER2). However, often develop resistance to trastuzumab via signaling from alternative receptors that converge activate guanine nucleotide exchange factors (GEFs) in turn Rho GTPases Rac Cdc42. Since Cdc42 have been implicated high tumor grade therapy resistance, inhibiting activity is a rational strategy overcome HER2-targeted resistance....
Alle Selektivitätskriterien der katalytischen asymmetrischen Aminohydroxylierung mit Sulfonamiden [GI. (a)] werden verbessert, wenn statt des ursprünglich für diese Reaktionen verwendeten Chloramin‐T dessen Methyl‐Analogon Chloramin‐M 1 eingesetzt wird. Dieses neu eingeführte Reagens weist eine deutlich höhere Ligandenabhängigkeit auf, und die meisten Substrate tritt das erwünschte Phänomen ligandenbeschleunigten Katalyse auf. DHQ‐H = Dihydrochinin, PHAL 1,3‐Phthalazindiyl. magnified image