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Articles 1 - 18 of 18
Full-Text Articles in Physical Sciences and Mathematics
Evidence Of Direct Interaction Between Cisplatin And The Caspase-Cleaved Prostate Apoptosis Response-4 Tumor Suppressor, Krishna K. Raut, Samjhana Pandey, Gyanendra Kharel, Steven M. Pascal
Evidence Of Direct Interaction Between Cisplatin And The Caspase-Cleaved Prostate Apoptosis Response-4 Tumor Suppressor, Krishna K. Raut, Samjhana Pandey, Gyanendra Kharel, Steven M. Pascal
Chemistry & Biochemistry Faculty Publications
Prostate apoptosis response-4 (Par-4) tumor suppressor protein has gained attention as a potential therapeutic target owing to its unique ability to selectively induce apoptosis in cancer cells, sensitize them to chemotherapy and radiotherapy, and mitigate drug resistance. It has recently been reported that Par-4 interacts synergistically with cisplatin, a widely used anticancer drug. However, the mechanistic details underlying this relationship remain elusive. In this investigation, we employed an array of biophysical techniques, including circular dichroism spectroscopy, dynamic light scattering, and UV–vis absorption spectroscopy, to characterize the interaction between the active caspase-cleaved Par-4 (cl-Par-4) fragment and cisplatin. Additionally, elemental analysis was …
Synthesis, Characterization, And Antiproliferative Activity Of Novel Chiral [Quinoxp*Aucl2]+ Complexes, Adedamola S. Arojojoye, R. Tyler Mertens, Samuel Ofori, Sean R. Parkin, Samuel G. Awuah
Synthesis, Characterization, And Antiproliferative Activity Of Novel Chiral [Quinoxp*Aucl2]+ Complexes, Adedamola S. Arojojoye, R. Tyler Mertens, Samuel Ofori, Sean R. Parkin, Samuel G. Awuah
Chemistry Faculty Publications
Herein is reported the synthesis of two Au(III) complexes bearing the (R,R)-(–)-2,3-Bis(tert-butylmethylphosphino)quinoxaline (R,R-QuinoxP*) or (S,S)-(+)-2,3-Bis(tert-butylmethylphosphino)quinoxaline (S,S-QuinoxP*) ligands. By reacting two stoichiometric equivalents of HAuCl4.3H2O to one equivalent of the corresponding QuinoxP* ligand, (R,R)-(–)-2,3-Bis(tert-butylmethylphosphino)quinoxalinedichlorogold(III) tetrachloroaurates(III) (1) and (S,S)-(+)-2,3-Bis(tert-butylmethylphosphino)quinoxalinedichlorogold(III) tetrachloroaurates(III) (2) were formed, respectively, in moderate yields. The structure of (S,S)-(+)-2,3-Bis(tert-butylmethylphosphino)quinoxalinedichlorogold(III) tetrachloroaurates(III) (2) was further confirmed by X-ray crystallography. The antiproliferative activities of the two compounds were evaluated in a panel of cell lines and exhibited promising results comparable to auranofin and cisplatin with …
Interaction Of A Platinum Triamine Complex Having A Seven-Membered Chelate Ring With N-Acetyl-Lmethionine And Guanosine 5'-Monophosphate, Jae Ko
Masters Theses & Specialist Projects
In the 1960s, Rosenberg and his colleagues confirmed the anti-cancer activity of cisplatin. Although cisplatin was capable of killing testicular cancer cells there were also serious side effects. It was necessary to find alternate ways of overcoming side effects, and soon many researchers have discovered novel platinum compounds that show similar reactivity. Recently, replacing one chloride group to a heterocyclic amine group showed significant cytotoxicity with a different binding activity than cisplatin. Previously in our lab, [Pt(Me5dien)(NO3)]+ and [Pt(Et2dien)Cl]+ have been synthesized and reacted with NAcetyl- L-methionine (N-AcMet) and Guanosine 5’-monophosphate (5’-GMP) showed unusual reactivity. Unlike most previously studied platinum …
Effects Of Binding Affinity Between Bovine Serum Albumin And Platinum Drugs, Nathan Puckett
Effects Of Binding Affinity Between Bovine Serum Albumin And Platinum Drugs, Nathan Puckett
Masters Theses & Specialist Projects
Platinum complex drugs such as cisplatin have been used as highly successful chemotherapy drugs since the 1970s. We are interested in how the ligands attached to cisplatin analogs influences their reactivity with biologically relevant targets along with time and amount. For this study, reactions were conducted to determine the reactivity between different platinum compounds and the protein bovine serum albumin. Various platinum compounds with different ligands were reacted in varying amounts with albumin in ammonium acetate buffer for either 1 hour, 4 hours, or 24 hours. Each reaction was quenched after the designated reaction time by dialysis and the platinum …
Relative Reaction Rates Of The Amino Acids Cysteine, Methionine, And Histidine With Analogs Of The Anti-Cancer Drug Cisplatin, Cynthia A. Tope
Relative Reaction Rates Of The Amino Acids Cysteine, Methionine, And Histidine With Analogs Of The Anti-Cancer Drug Cisplatin, Cynthia A. Tope
Mahurin Honors College Capstone Experience/Thesis Projects
We are studying the reaction of analogs of the anticancer drug cisplatin with amino acids that differ in size and shape. The reaction of cisplatin with proteins likely precedes reaction with DNA in the body, forming a variety of products that may be toxic to the human body. The size and shape of the platinum(II) complexes often affects the rate of reaction with proteins, more so than with DNA. In this study, triamine cisplatin analogs are reacted with the amino acids cysteine, methionine, and histidine simultaneously. These reactions are monitored by NMR spectroscopy. The effect of the bulk of the …
The Interaction Of Glutathione With Platinum, And The Role Of Ph In Altering Ligand Formation Between Platinum And N-Acetylcysteine, Kyle B. Mann
Mahurin Honors College Capstone Experience/Thesis Projects
Cisplatin is an important anti-cancer drug. Structurally, cisplatin is a coordination complex, which means that it has a central metallic atom: platinum. Side interactions prevent cisplatin from effectively treating cancerous cells by reaction with DNA. Cisplatin has a high rate of forming protein adducts, primarily with sulfur containing amino acids. To better understand how cisplatin interacts with sulfur containing amino acids in the body, a platinum compound with an ethylenediamine ligand attached was reacted with N-acetylcysteine and glutathione. The reactions of cysteine with platinum were performed at three pH values: 7.0, 8.5, and 10. NMR spectroscopy was used to examine …
Reaction Rates Of Amino Acids With Derivatives Of The Anticancer Drug Cisplatin, Celia Jess Whelan
Reaction Rates Of Amino Acids With Derivatives Of The Anticancer Drug Cisplatin, Celia Jess Whelan
Mahurin Honors College Capstone Experience/Thesis Projects
We are studying reactions of cisplatin derivatives, which differ in both size and shape, with various amino acids. When reaction with DNA occurs, apoptosis is observed, ideally leading to termination of the cancer. Due to the affinity of cisplatin for sulfur-containing amino acids, reaction with proteins may occur prior to access to the DNA, producing a large array of products, which could potentially be toxic to the human body. Both the size and shape of the platinum complexes often affect the reactions with protein targets more so than with DNA targets. By performing reactions of specific amino acids targets with …
Effect Of Leaving Ligands Of Platinum(Ii) Diamine Complexes On Dna And Protein Residues, Ramya Kolli
Effect Of Leaving Ligands Of Platinum(Ii) Diamine Complexes On Dna And Protein Residues, Ramya Kolli
Masters Theses & Specialist Projects
Platinum compounds are widely used drugs in cancer treatments. Although DNA is the biological target, reaction of platinum compounds with proteins is also potentially significant. Our objective is to study the effects of leaving ligands on the relative reactivity between 5'-GMP (guanosine 5' phosphate), a key DNA target, and N-Acetyl - L-Methionine (N-AcMet), a key protein target. We have used NMR spectroscopy to monitor reactions with N-AcMet and 5'-GMP added to a platinum complex to see which products are formed preferentially. Previous research showed that both a non-bulky complex such as [Pt(en)(D2O)2]2+ [en=ethylenediamine], and a …
Reactions Of Platinum(Ii) Compounds With Selenium Containing Amino Acids, Stephanie Robey
Reactions Of Platinum(Ii) Compounds With Selenium Containing Amino Acids, Stephanie Robey
Masters Theses & Specialist Projects
Platinum(II) anticancer medications essentially react with DNA forming kinks in
the double helix of DNA and causing apoptosis. It has also been noted that these
anticancer medications react with methionine and cysteine in the body. With the new discoveries of selenium containing amino acids including selenomethionine and selenocysteine, new research is ongoing to see what types of products can be formed from these amino acids. Our research reacts [Pt(Met-S,N)Cl2] 2+ with selenomethionine to determine what types of products are produced. Monochelates including [Pt(SeMet-Se,N)Cl2] 2+ have formed two isomers, …
Dimethyl Sulfoxide (Dmso) Exacerbates Cisplatin-Induced Sensory Hair Cell Death In Zebrafish (Danio Rerio), Phillip M. Uribe, Melissa A. Mueller, Julia S. Gleichman, Matthew D. Kramer, Qi Wang, Martha Sibrian-Vazquez, Robert M. Strongin, Peter S. Steyger, Douglas A. Cotanche, Jonathan I. Matsui
Dimethyl Sulfoxide (Dmso) Exacerbates Cisplatin-Induced Sensory Hair Cell Death In Zebrafish (Danio Rerio), Phillip M. Uribe, Melissa A. Mueller, Julia S. Gleichman, Matthew D. Kramer, Qi Wang, Martha Sibrian-Vazquez, Robert M. Strongin, Peter S. Steyger, Douglas A. Cotanche, Jonathan I. Matsui
Chemistry Faculty Publications and Presentations
Inner ear sensory hair cells die following exposure to aminoglycoside antibiotics or chemotherapeutics like cisplatin, leading to permanent auditory and/or balance deficits in humans. Zebrafish (Danio rerio) are used to study drug-induced sensory hair cell death since their hair cells are similar in structure and function to those found in humans. We developed a cisplatin dose-response curve using a transgenic line of zebrafish that expresses membrane-targeted green fluorescent protein under the control of the Brn3c promoter/enhancer. Recently, several small molecule screens have been conducted using zebrafish to identify potential pharmacological agents that could be used to protect sensory hair cells …
The Reaction Of Methionine With A Non-C2-Symmetrical Platinum (Ii) Diamine Compound, Nilesh Sahi
The Reaction Of Methionine With A Non-C2-Symmetrical Platinum (Ii) Diamine Compound, Nilesh Sahi
Mahurin Honors College Capstone Experience/Thesis Projects
The research that we have conducted has allowed us to discover that the amino acids, methionine (Met) and N-acetyl methionine (N-AcMet), will react in a 1:1 and 1:2 molar ratio with platinum complexes containing bulky diamine ligands. Previous research has allowed us to gain a plethora of information on the experimentation and results of specific bulky diamine ligands such as N,N,N',N'-tetramethylethylenediamine and N,N-diethylethylenediamine. In the current study, we have investigated the bulky diamine ligand of N,N-dimethylethylenediamine, or Me2en. With our focus on the bulk of the Me2en ligand, we have been able to synthesize a platinum …
Oxaliplatin And Oxaliplatin Derivatives: Synthesis, Characterization, And Reactivity With Biologically Relevant Ligands, Amy Poynter
Mahurin Honors College Capstone Experience/Thesis Projects
Oxaliplatin is a third generation anticancer drug that has proven to be successful in fighting ovarian and testicular cancer. We are interested in determining how oxaliplatin and oxaliplatin derivatives interact with proteins, as well as how that interaction is affected by the size and shape of these platinum compounds. We have synthesized oxaliplatin as it is used in cancer treatment, as well as similar platinum compounds with the same diaminocyclohexane ligand as oxaliplatin but with additional bulk added to the nitrogen atoms. We are reacting oxaliplatin with key amino acids, including methionine, and will be comparing the kinetics of this …
Reactions With Platinum (Ll) Complexes And Selenium-Containing Amino Acids, Stephanie Robey
Reactions With Platinum (Ll) Complexes And Selenium-Containing Amino Acids, Stephanie Robey
Mahurin Honors College Capstone Experience/Thesis Projects
We have reacted [Pt(Me4en)(D2O)2]2+ [Me4En=N,N,N’N’-tetramethylethylenediamine] with Selenomethionine (SeMet), Methionine (Met), and Methylselenocysteine (MeSeCys). When MeSeCys was reacted with [Pt(Me4en)(D2O)2]2+, we observed both stereoisomers of Se,N chelates, as well as [Pt(Me4en)(MeSeCys)Cl]+ from 1H NMR Spectroscopy; the latter formed due to the presence of Cl- in the solution. Both isomers of the chelate seemed to form proportionally to one another, not favoring a specific stereoisomer. Eventually the [Pt(Me4en)(MeSeCys)Cl]+ products became Se,N chelates. We incubated SeMet with …
Inhibition Of Cysteine Protease By Platinum (Ii) Diamine Complexes, Chaitanya Rapolu
Inhibition Of Cysteine Protease By Platinum (Ii) Diamine Complexes, Chaitanya Rapolu
Masters Theses & Specialist Projects
Chemotherapy is the first line of treatment used in cancer. Chemotherapy drugs such as cisplatin, carboplatin and oxaliplatin are used in treatment. Cisplatin enters the cell through copper transporter CTR1 by passive diffusion and bind to DNA and proteins. Cisplatin is found to inhibit several enzymes targeting cysteine, histidine and methionine residues, which are expected to be responsible for its anticancer activity. A better understanding of how the size and shape and leaving ligands of platinum complexes affect cysteine protease, papain enzyme are studied. This could give new ways to optimize anticancer activity. The activity of papain enzyme was measured …
The Reaction Of A Water Soluble Platinum Compound With Methionine And Derivatives, Yueh Ying Liao
The Reaction Of A Water Soluble Platinum Compound With Methionine And Derivatives, Yueh Ying Liao
Masters Theses & Specialist Projects
Water soluble platinum complexes are a recent area of emphasis of cisplatin chemistry. The water soluble complexes could have a reduced toxicity compared with cisplatin. Oxaliplatin, which has an oxalate leaving group, has previously been shown to have less nephro-toxicity and higher water solubility than cisplatin. [Pt(en)(oxalate)] (en = ethylenediamine) has been prepared from Pt(en)Cl2 and silver oxalate. This complex has been reacted with methionine and N-acetylmethionine at different molar ratios. At high Pt: methionine ratios, chelates with the sulfur and nitrogen atoms of the methionine are dominant; at lower Pt: methionine ratios, a bis-methionine product is formed. The en …
Reactions Of Cisplatin Analogs With Selenomethionine, Rebekkah Lively
Reactions Of Cisplatin Analogs With Selenomethionine, Rebekkah Lively
Mahurin Honors College Capstone Experience/Thesis Projects
Cisplatin is a well-known anti-cancer drug that is effective, but also has some severe and unwanted side effects. Analogs of cisplatin were reacted with the nonstandard amino acid selenomethionine (SeMet), and the products were characterized by 1H and 195Pt NMR spectroscopy and HPLC. In previous studies, SeMet was found to react faster than methionine (Met) with a representative platinum complex (Pt(dien)Cl2), therefore SeMet is said to react faster kinetically. Thus, while only a subset of proteins have selenium-containing amino acids, platinum complexes could target them kinetically. Cisplatin analogs with two leaving groups have also been studied. Pt(Me4en)(NO3)2 (Me4en = N,N,N’,N’-tetramethylethylenediamine) …
Formation Of Monofunctional Cisplatin-Dna Adducts In Carbonate Buffer, Alexandra Binter, Jerry Goodisman, James C. Dabrowiak
Formation Of Monofunctional Cisplatin-Dna Adducts In Carbonate Buffer, Alexandra Binter, Jerry Goodisman, James C. Dabrowiak
Chemistry - All Scholarship
Carbonate in its various forms is an important component in blood and the cytosol. Since, under conditions that simulate therapy, carbonate reacts with cisplatin to form carbonato complexes, one of which is taken up and/or modified by the cell [C.R. Centerwall, J. Goodisman, D.J. Kerwood, J. Am. Chem. Soc., 127 (2005) 12768–12769], cisplatin-carbonato complexes may be important in the mechanism of action of cisplatin. In this report we study the binding of cisplatin to pBR322 DNA in two different buffers, using gel electrophoresis. In 23.8 mM HEPES, N-(2-hydroxyethyl)-piperazine-N′-2-ethanesulfonic acid, 5 mM NaCl, pH 7.4 buffer, cisplatin produces …
Constancy In Integrated Cisplatin Plasma Concentrations Among Pediatric Patients, Jerry Goodisman, Abdul-Kader Souid
Constancy In Integrated Cisplatin Plasma Concentrations Among Pediatric Patients, Jerry Goodisman, Abdul-Kader Souid
Chemistry - All Scholarship
The authors report on the variability in the integrated quantity of free (unbound) plasma cisplatin (area under curve of plasma concentration versus time, AUC). The AUC was measured in 19 patients receiving cisplatin doses proportional to body surface areas (BSA), 30mg/m2 over 1 hour. The relative standard deviation (RSD, population standard deviation divided by mean value) for the maximum free plasma cisplatin concentration (Cmax, μM) was 0.338; for the half-life (t½, minute), 0.210; and for the AUC (μM minute), 0.320. Thus, BSA-based dosing gave significant variability in the AUC. We attempted to use (weight)a(height)b, seeking values of a and b …