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1.
J Clin Ultrasound ; 52(2): 124-130, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37933208

ABSTRACT

PURPOSE: To evaluate correlation between serum iron parameters and liver T2* value in hemodialysis patients with iron overload due to parenteral iron therapy. MATERIALS AND METHODS: We evaluated 30 hemodialysis patients using a multiecho T2*-weighted MRI sequence. Age, sex, duration of dialysis, iron and erythropoietin doses taken in the past year, and serum iron parameters were recorded. Liver T2* values were averaged from three distinct liver regions. A T2* value of 33 ± 7 ms is considered normal. Declines below 24, 21, and 14 ms signify iron overload grades 1, 2, and 3, respectively. RESULTS: There was no statistically significant difference comparing the measurements of 3 different ROIs (p > 0.05). A total of 23 patients (76.6%) had iron overload. Serum ferritin levels of patients with iron overload were significantly higher than those without iron overload (687.25 [186.5-1489] ng/mL vs. 371.25 [127.5-542.5] ng/mL, p = 0.008). No linear correlation was observed between age, dialysis duration, serum iron metrics, medication doses, and T2* values. Likewise, no significant differences were found among patients based on iron overload status or its grades concerning these parameters. CONCLUSION: While standard serum markers might overlook iron overload, elevated ferritin levels are promising. MRI reliably detects iron overload in patients receiving parenteral iron.


Subject(s)
Ferritins , Iron Overload , Humans , Iron Overload/diagnostic imaging , Iron Overload/etiology , Iron/metabolism , Liver/diagnostic imaging , Liver/metabolism , Renal Dialysis/adverse effects , Magnetic Resonance Imaging
2.
Chem Biodivers ; 21(2): e202301422, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38156745

ABSTRACT

The extracellular signal-regulated kinase (ERK) - mitogen-activated protein kinase (MAPK) pathway regulates cell proliferation, differentiation, and apoptosis. Heat Shock Protein 90 (HSP90) is required to activate proto-oncogenic protein kinases and promotes tumor growth through anti-apoptotic effects on A549-non-small cell lung cancer (NSCLC). Therefore, deregulation of the ERK-MAPK pathway and abnormal expression of HSP90 are reasonably frequent events in NSCLC. In this study, novel perimidine-pyrazole compounds employed to block ERK-MAPK deregulation through inhibiting HSP dependent cancer cell survival mechanisms. A set of perimidine-pyrazole derivatives effects was monitored on NSCLC cell line. Array experiments performed to understand the effect of the compounds on signaling pathways and results were analyzed by gene enrichment analysis. Further, senescence and apoptosis experiments were performed to support the enrichment results along with in silico methods to determine perimidine-pyrazole/HSP interactions. Treatment of NSCLC cells with perimidine-pyrazole derivatives displayed cancer-inhibitory, pro-senescent and pro-apoptotic effects on NSCLC cells through ERK/MAPK pathway and these compounds are promising templates for designing anticancer drugs.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/pathology , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , MAP Kinase Signaling System , Cell Line, Tumor , Signal Transduction , Extracellular Signal-Regulated MAP Kinases/metabolism , Cell Proliferation , Pyrazoles/pharmacology , Pyrazoles/therapeutic use , Epithelial Cells/metabolism , Epithelial Cells/pathology , Apoptosis
3.
Mol Neurobiol ; 2023 Dec 18.
Article in English | MEDLINE | ID: mdl-38105408

ABSTRACT

In the 1980s, the identification of specific pharmacological antagonists played a crucial role in enhancing our comprehension of the physiological mechanisms associated with α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (AMPARs). The primary objective of this investigation was to identify specific AMPA receptor antagonists, namely 2,3-benzodiazepines, that function as negative allosteric modulators (NAMs) at distinct locations apart from the glutamate recognition site. These compounds have exhibited a diverse array of anticonvulsant properties. In order to conduct a more comprehensive investigation, the study utilized whole-cell patch-clamp electrophysiology to analyze the inhibitory effect and selectivity of benzodiazepine derivatives that incorporate coumarin rings in relation to AMPA receptors. The study's main objective was to acquire knowledge about the relationship between the structure and activity of the compound and comprehend the potential effects of altering the side chains on negative allosteric modulation. The investigation provided crucial insights into the interaction between eight CD compounds and AMPA receptor subunits. Although all compounds demonstrated effective blockade, CD8 demonstrated the greatest potency and selectivity towards AMPA receptor subunits. The deactivation and desensitization rates were significantly influenced by CD8, CD6, and CD5, distinguishing them from the remaining five chemicals. The differences in binding and inhibition of AMPA receptor subunits can be attributed to structural discrepancies among the compounds. The carboxyl group of CD8, situated at the para position of the phenyl ring, substantially influenced the augmentation of AMPA receptor affinity. The findings of this study highlight the potential of pharmaceutical compounds that specifically target AMPA receptors to facilitate negative allosteric modulation.

4.
J Biomol Struct Dyn ; 41(23): 14382-14397, 2023.
Article in English | MEDLINE | ID: mdl-36826447

ABSTRACT

Intensive studies on hepatocellular carcinoma (HCC), which is spreading rapidly around the world and has a high mortality rate, is due to the lack of adequate preventive or curative treatment methods. Treating patients with HCC has become very challenging because of the heterogeneity in the patient population lead activation of different signaling pathways, and pathway crosstalk for patients. Therefore, understanding these molecular mechanisms and combining drugs with molecular therapies to overcome these drawbacks has become an area of utmost importance. In this study, the biological activities of the designed and characterized triad Pyrazole-Thiazol-Coumarin (PTC) compounds were determined by performing cell viability, qPCR array, apoptosis and cell cycle assays. One of the compounds (PTC10) implicitly suppresses multiple pathways (RAS/MAP kinase and PI3K-AKT) simultaneously. This action is provided by (i) arresting cancer cells at G2 phase, (ii) driving cancer cells to apoptosis and (iii) inhibiting HSP network. Remarkably, HSP is an apoptotic factor and help cancer cell to survive. HSP90 also coordinates with Cdk4/Cdc37, therefore inhibiting HSP both drives cells to arrest and apoptosis. ATP hydrolysis and aggregation assay further displayed specific HSP inhibition. Therefore, PTC provides a unique drug template for HCC treatment.


Subject(s)
Antineoplastic Agents , Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/drug therapy , Liver Neoplasms/drug therapy , Phosphatidylinositol 3-Kinases/metabolism , Phosphatidylinositol 3-Kinases/pharmacology , Phosphatidylinositol 3-Kinases/therapeutic use , Thiazoles/pharmacology , Pyrazoles/pharmacology , Apoptosis , Coumarins/pharmacology , Cell Proliferation , Cell Line, Tumor , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use
5.
Arch Pharm (Weinheim) ; 355(1): e2100242, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34609760

ABSTRACT

Human carbonic anhydrase (hCA) isoenzymes are zinc ion-containing, widespread metalloenzymes and they classically play a role in pH homeostasis maintenance. CA inhibitors suppress the CA activity and their usage has been clinically established as antiglaucoma agents, antiepileptics, diuretics, and in some other disorders. Alzheimer's disease (AD) is a slowly progressive neurodegenerative disorder and a fatal disease of the brain. An advanced method to cure AD includes the strategy to design acetylcholinesterase (AChE) inhibitors. A novel series of pyrrole-3-one derivatives containing sulfa drugs (5a-i) were determined to be highly potent inhibitors for AChE and hCA I and hCA II (inhibitory constant [Ki ] values are in the range of 6.50 ± 1.02-37.46 ± 4.12 nM, 1.20 ± 0.19-44.21 ± 1.09 nM, and 8.93 ± 1.58-46.86 ± 8.41 nM for AChE, hCA I, and hCA II, respectively). The designed compounds often show a more effective inhibition than the chemicals used as the standard. Among these compounds, 5f was the most effective compound against hCA I, and compound 5e was the most effective compound against hCA II. It was determined that compound 5c was the most effective inhibitor for AChE.


Subject(s)
Carbonic Anhydrase Inhibitors/pharmacology , Cholinesterase Inhibitors/pharmacology , Pyrroles/pharmacology , Sulfonamides/pharmacology , Carbonic Anhydrase I/antagonists & inhibitors , Carbonic Anhydrase II/antagonists & inhibitors , Carbonic Anhydrase Inhibitors/chemical synthesis , Carbonic Anhydrase Inhibitors/chemistry , Cholinesterase Inhibitors/chemical synthesis , Cholinesterase Inhibitors/chemistry , Humans , Isoenzymes , Pyrroles/chemical synthesis , Pyrroles/chemistry , Structure-Activity Relationship , Sulfonamides/chemical synthesis , Sulfonamides/chemistry
6.
J Biomol Struct Dyn ; 40(19): 8655-8671, 2022.
Article in English | MEDLINE | ID: mdl-33890547

ABSTRACT

A novel series of pyrrole-3-one derivatives were synthesized using furan-3-one derivatives and various aromatic amines. The synthesized compounds were identified by spectral studies such as IR, NMR and HRMS. Dielectric properties of the target compounds were experimentally determined by dielectric spectroscopy in the frequency range of 20 Hz - 1 MHz. The real part of the dielectric constant, dielectric loss tangent and conductivity of the samples were investigated as a function of applied frequency. Dielectric measurements showed Ata7 has the maximum dielectric constant at 1 kHz, while Ata1 has a negative dielectric constant value. When the result is evaluated with theoretical calculations, grain boundaries play an effective role in the experimental observed dielectric constant. Additionally, in this research the pyrrole-3-one derivatives (Ata1-9) were theoretically optimized and over these structures, NMR with GIAO (gauge-independent atomic orbital), UV with TD (time dependent), frontier orbitals (HOMO and LUMO), NLO (nonlinear optical properties) and MEP (molecular electrostatic potential) analysis were carried out. Quantum chemical computations were performed by Density Functional Theory (DFT) using B3LYP functional and 6-311++G (d,p) basis set. Later, the molecular docking analysis between Ata1-9 and two different receptors such as 3RZE and 3TDA was performed using AutoDock Vina program. Lastly, drug-likeness, physicochemical and ADME/T properties of the designed compounds were computed with the help of SwissADME online tool.Communicated by Ramaswamy H. Sarma.


Subject(s)
Pyrroles , Spectrum Analysis, Raman , Molecular Docking Simulation , Models, Molecular , Spectroscopy, Fourier Transform Infrared , Quantum Theory , Spectrophotometry, Ultraviolet , Thermodynamics
7.
Anticancer Agents Med Chem ; 21(11): 1472-1480, 2021.
Article in English | MEDLINE | ID: mdl-32951578

ABSTRACT

BACKGROUND: HSP70 is a survival factor for tumor cells in transformation and in tumor progression as well as in anti-apoptotic response. OBJECTIVE: Several inhibitors targeting HSP70 ATPase function displayed off-target effects, but PES, which targets the HSP70 substrate binding domain, prevents tumor cell survival prominently. However, PES may not bind HSP70 in the absence of nucleotide. This research aimed to design a unique inhibitor molecule that works both in the presence and absence of nucleotides to amplify inhibition. METHODS: A set of chimeric coumarine-pyrazole derivatives were determined by in silico techniques and synthesized to elucidate their inhibitory effects. Cell viability experiments displayed KBR1307 as the most efficient inhibitor. A set of characterization experiments were performed, and the results were compared to that of PES agent. Binding constant, ATP hydrolysis rate, and percent aggregation were determined in the presence and absence of inhibitors. RESULTS: In silico docking experiments showed that only KBR1307 binds the HSP70 substrate binding domain and interacts with cochaperone interface. Binding experiments indicated that KBR1307 binds HSP70 both in the presence and absence of nucleotides, but PES does not. Both inhibitors significantly lower HSP70 ATPase activity and substrate protein disaggregation activity. However, KBR1307 displays a lower IC50 value at the MCF-7 cell line compared to PES. Both inhibitors do not alter HSP70 secondary structure composition and overall stability. CONCLUSION: KBR1307 effectively inhibits HSP70 compared to PES and provides a promising template for novel anticancer drug development.


Subject(s)
Antineoplastic Agents/pharmacology , Coumarins/pharmacology , Drug Design , HSP70 Heat-Shock Proteins/antagonists & inhibitors , Pyrazoles/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Proliferation/drug effects , Cell Survival/drug effects , Coumarins/chemistry , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Humans , MCF-7 Cells , Molecular Structure , Protein Folding/drug effects , Pyrazoles/chemistry , Structure-Activity Relationship
8.
Future Med Chem ; 11(15): 1979-1998, 2019 08.
Article in English | MEDLINE | ID: mdl-31517529

ABSTRACT

Thiazoles have attracted much synthetic interest due to their wide variety of biological properties and are important members of heterocyclic compounds. In recent years, studies on the synthesis of thiazole compounds have been increasing because of the properties of this core. In particular, the hybrid structures in which the thiazole ring and the other nuclei are linked have gained popularity. Hybrid structures are formed by the combination of different groups of chemical reactivity and biological activity characteristics. In this review, we highlight recent developments related to hybrid structures containing a thiazole core, recently developed as anticancer, antibacterial, anti-inflammatory, analgesic, anti-tubercular, antialzheimer and antidiabetic compounds.


Subject(s)
Anti-Inflammatory Agents/chemistry , Thiazoles/chemistry , Animals , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Inflammatory Agents/metabolism , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Cell Survival/drug effects , Cyclooxygenase 2/chemistry , Cyclooxygenase 2/metabolism , Diabetes Mellitus/drug therapy , Diabetes Mellitus/pathology , Humans , Hypoglycemic Agents/chemistry , Hypoglycemic Agents/therapeutic use , Structure-Activity Relationship , Thiazoles/metabolism
9.
Int J Radiat Biol ; 93(7): 705-710, 2017 07.
Article in English | MEDLINE | ID: mdl-28281400

ABSTRACT

PURPOSE: To evaluate thiol-disulphide homeostasis - a novel, easily calculated, readily available, and relatively cheap oxidative stress marker - in radiation workers and compare the results with healthy controls. MATERIALS AND METHODS: A total of 108 participants were enrolled in the study including 63 hospital workers occupationally exposed to ionizing radiation in the units of interventional radiology, interventional cardiology and nuclear medicine. A control group consisted of 45 individuals staff in the same hospital. Serum thiol-disulphide homeostasis measurement was investigated via the spectrophotometric method newly described by Erel and Neselioglu. RESULTS: The mean serum native thiol levels of radiation workers (528.96 ± 86.42 µmol/l) was significantly lower than control subjects (561.05 ± 104.83 µmol/l) (p = .045). The mean serum total thiol levels of radiation workers (547.70 ± 91.50 µmol/l) was lower than control subjects (580.36 ± 112.24 µmol/l). Nevertheless, there was no significant difference between total thiol of exposed workers and controls. CONCLUSIONS: The results show that long-term low dose ionizing radiation may lead to oxidative stress and have side-effects in antioxidant thiol groups. We may suggest supporting radiation workers by safe antioxidant nutritional formulations and following up via both physical dosimetry and biodosimetric methods.


Subject(s)
Disulfides/blood , Medical Staff, Hospital/statistics & numerical data , Occupational Exposure/statistics & numerical data , Oxidative Stress/radiation effects , Radiation Exposure/statistics & numerical data , Sulfhydryl Compounds/blood , Adolescent , Adult , Biological Assay/methods , Dose-Response Relationship, Radiation , Female , Homeostasis/physiology , Homeostasis/radiation effects , Humans , Male , Middle Aged , Oxidative Stress/physiology , Radiation Dosage , Reproducibility of Results , Sensitivity and Specificity , Turkey/epidemiology , Young Adult
10.
J Ultrasound Med ; 35(12): 2623-2628, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27872419

ABSTRACT

OBJECTIVES: Elastography is a new sonographic technique that evaluates the elasticity of different tissues such as the Achilles tendon. In this study, we aimed to investigate the elastographic findings of Achilles tendons in professional athletes in comparison with healthy volunteers. METHODS: Twenty-one professional male volleyball players with no history of Achilles trauma were included in this study. Twenty-one healthy male volunteers with similar ages and body mass indices were selected as control participants. All participants underwent sonographic and elastographic evaluations of the Achilles tendons to evaluate Achilles tendon thickness and stiffness. RESULTS: We observed thickening in many of the thirds of the Achilles tendons (right proximal, right middle, left middle, and left distal thirds) of athletes in comparison with healthy volunteers. We did not detect any abnormalities according to the sonographic evaluations in both athletes and healthy volunteers. In the elastographic evaluations, we observed softening in the middle thirds of the Achilles tendons of athletes according to the main types (P < .001) and subtypes (P < .001 for right; and P = .002 for left middle third). There was no difference observed in the elastographic evaluations of the proximal and distal thirds. CONCLUSIONS: On sonography and elastography, we observed thickening and softening in Achilles tendons of athletes in comparison with healthy volunteers who had similar ages and body mass indices. These changes could be associated with early tendon degeneration. Further longitudinal studies may support this consideration.


Subject(s)
Achilles Tendon/diagnostic imaging , Athletes , Elasticity Imaging Techniques/methods , Volleyball , Adolescent , Adult , Humans , Male , Reference Values , Young Adult
11.
Curr Pharm Biotechnol ; 17(14): 1231-1245, 2016.
Article in English | MEDLINE | ID: mdl-27804852

ABSTRACT

BACKGROUND: Despite development of novel cancer drugs, invasive ductal breast carcinoma and its metastasis are still highly morbid. Therefore, new therapeutic approaches are being developed and Hsp90 is an important target for drug design. For this purpose, a series of benzodiazepine derivatives were designed and synthesized as novel Hsp90 inhibitor. METHODS: Benzodiazepine derivatives anticancer activities were determined by XTT cell proliferation assay against human breast cancer cell line (MCF-7). Effects of the compounds on endothelial function were monitored on human vascular endothelium (HUVEC) cell line as well. In order to determine the anti-proliferative mechanism of the compounds, in silico molecular docking studies were performed between Hsp90 ATPase domain and the benzodiazepine derivatives. Further, these compounds perturbation on Hsp90 ATPase function were tested. Fluorescence binding experiments showed that the derivatives bind Hsp90 effectively. Expression analysis of known cancer drug target genes by PCR array experiments suggest that the benzodiazepine derivatives have remarkable anticancer activity. RESULTS: A representative Benzodiazepine derivative D5 binds Hsp90 with Kd value of 3,93 µM and with estimated free energy of binding -7.99 (kcal/mol). The compound decreases Hsp90 ATPase function and inhibit Hsp90 client protein folding activity. The compound inhibits expression of both Hsp90 isoforms and key proteins (cell cycle receptors; PLK2 and TERT, kinases; PI3KC3 and PRKCE, and growth factors; IGF1, IGF2, KDR, and PDGFRA) on oncogenic pathways. CONCLUSION: Benzodiazepine derivatives presented here display anticancer activity. The compounds effect on both breast cancer and endothelial cell lines show their potential as drug templates to inhibit breast cancer and its metastasis.


Subject(s)
Antineoplastic Agents/pharmacology , Breast Neoplasms/metabolism , HSP90 Heat-Shock Proteins/antagonists & inhibitors , Antineoplastic Agents/chemical synthesis , Breast Neoplasms/drug therapy , Cell Line , Drug Design , Humans , Molecular Docking Simulation
12.
Ultrasound Q ; 32(4): 333-337, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27599308

ABSTRACT

OBJECTIVE: To investigate the significance of ultrasound elastography for evaluating the optic nerve in patients with primary open angle glaucoma (POAG). METHODS: This prospective, comparative case series included 40 eyes of 40 patients. Twenty eyes with POAG comprised the POAG group, and 20 eyes of 20 patients without glaucoma who admitted to general eye clinic for near vision glasses comprised the control group. All real-time sonographicelastographic examinations were performed by the same physician. The ratio of orbital fat to optic nerve head (ROFON) and lateral rectus to optic nerve head (RLRON) were determined. Statistical analyses were performed using Student t test, Kolmogorov-Smirnov test, and χ test. RESULTS: The mean ages of the patients in the study and the control groups were 65.10 ± 7.88 years (range, 48-80 years), and 69.15 ± 7.92 years (range, 55-89 years), respectively (P = 0.113). Mean ROFONs were 1.85 and 6.42 (P < 0.05), and mean RLRONs were 0.65 and 1.07 (P < 0.05) in the control and POAG groups, respectively. CONCLUSIONS: Real-time elastography showed increased ROFON and RLRON in POAG patients. This can help to understand optic nerve head biomechanics and clarify glaucoma damage in early glaucoma cases.


Subject(s)
Elasticity Imaging Techniques/methods , Glaucoma, Open-Angle/diagnostic imaging , Optic Nerve/diagnostic imaging , Aged , Aged, 80 and over , Computer Systems , Female , Humans , Male , Middle Aged , Prospective Studies
13.
Eur J Med Chem ; 122: 280-290, 2016 Oct 21.
Article in English | MEDLINE | ID: mdl-27376491

ABSTRACT

Invasive ductal carcinoma is the most common breast malignancies tumors and has tendency to bone metastases. Many oncogenic client proteins involved in formation of metastatic pathways. Stabilization, regulation, and maintenance of these oncogenic client proteins are provided with Heat Shock Protein 90 (Hsp90). Hsp90 perform these processes through its ATP binding and subsequent hydrolysis energy. Therefore, designing Hsp90 inhibitors is a novel cancer treatment method. However, many Hsp90 inhibitors have solubility problems and showed adverse effects in clinical trials. Thus, we designed and synthesized novel pyrimidinyl acyl thiourea derivatives to selectively inhibit Hsp90 alpha in human invasive ductal breast (MCF-7) and human bone osteosarcoma (Saos-2) cell lines. In vitro experiments showed that the compounds inhibited cell proliferation, ATP hydrolysis, and exhibited cytotoxic effect on these cancer cell lines. Further, gene expression was analyzed by microarray studies on MCF-7 cell lines. Several genes that play vital roles in breast cancer pathogenesis displayed altered gene expression in the presence of a selected pyrimidinyl acyl thiourea compound. Molecular docking studies were also performed to determine interaction between Hsp90 ATPase domain and pyrimidinyl acyl thiourea derivatives. The results indicated that the compounds are able to interact with Hsp90 ATP binding pocket and inhibit ATPase function. The designed compounds powerfully inhibit Hsp90 by an average of 1 µM inhibition constant. And further, the compounds perturb Hsp90 N terminal domain proper orientation and ATP may not provide required conformational change for Hsp90 function as evidenced by in silico experiments. Therefore, the designed compounds effectively inhibited both invasive ductal breast carcinoma and bone metastasis. Pyrimidinyl acyl thiourea derivatives may provide a drug template for effective treatment of invasive ductal breast carcinoma and its bone metastasis as well as new therapeutic perspective for drug design.


Subject(s)
Bone Neoplasms/secondary , Carcinoma, Ductal, Breast/pathology , Drug Design , HSP90 Heat-Shock Proteins/antagonists & inhibitors , Thiourea/chemical synthesis , Thiourea/pharmacology , Adenosine Triphosphatases/antagonists & inhibitors , Adenosine Triphosphate/metabolism , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Bone Neoplasms/pathology , Cell Line, Tumor , Cell Proliferation/drug effects , HSP90 Heat-Shock Proteins/chemistry , Humans , Hydrolysis/drug effects , Molecular Docking Simulation , Protein Conformation, beta-Strand , Thiourea/chemistry
14.
Anticancer Agents Med Chem ; 15(7): 916-30, 2015.
Article in English | MEDLINE | ID: mdl-25846761

ABSTRACT

Inhibition of the Hsp90 function is an essential therapeutic approach and several inhibitors were designed as anti-cancer agents. These inhibitors are ATPases and they aim to deregulate Hsp90 folding function. ATPase proteins are common in human metabolism but they form nonspecific targets. Hsp90 functions as dimer with coordinating chaperones. Heat Shock Organizing Protein (Hop) forms a bridge between Hsp90 and Hsp70-Hsp40 complex to form Hsp90-Hsp70 coordination. Perturbing conformational changes of these Hsp proteins, dimer formation, and protein-protein interactions inhibit Hsp90 substrate protein folding function. This approach does not target all ATPase proteins but targets Hsp90 function solely. For this purpose, we designed compounds to block Hsp90 function. Moreover, molecular docking studies as well as competition analysis of the compounds were performed with Hsp90. Novel thiazolyl coumarine compounds were determined as valuable C-terminal Hsp90 inhibitors and provide promising templates for the drug design. Anticancer activities of these novel compounds were tested by employing human colon (DLD-1) and liver cancer (HepG2) cell lines. Thiazolyl coumarine compounds are found to be significant and useful for the treatment of human colon and liver cancer as evidenced by in vitro and in silico results.


Subject(s)
Antineoplastic Agents/chemistry , Coumarins/chemistry , HSP90 Heat-Shock Proteins/antagonists & inhibitors , Heat-Shock Response/drug effects , Thiazoles/chemistry , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Cell Proliferation/drug effects , Coumarins/chemical synthesis , Coumarins/pharmacology , Humans , Molecular Docking Simulation , Structure-Activity Relationship , Thiazoles/chemical synthesis , Thiazoles/pharmacology
15.
Spectrochim Acta A Mol Biomol Spectrosc ; 118: 816-27, 2014 Jan 24.
Article in English | MEDLINE | ID: mdl-24152866

ABSTRACT

We have synthesized ethyl (2E)-3-amino-2-({[(4-benzoyl-1,5-diphenyl-1H-pyrazol-3-yl)carbonyl]amino}carbonothioyl)but-2-enoate (2) by the reaction of 4-benzoyl-1,5-diphenyl-1H-pyrazole-3-carbonyl chloride (1), ammonium thiocyanate and ethyl 3-aminobut-2-enoate and then characterized by elemental analyses, IR, Raman, (1)H NMR, (13)C NMR and X-ray diffraction methods. The experimental and theoretical vibrational spectra of 2 were investigated. The experimental FT-IR (4000-400 cm(-1)) and Laser-Raman spectra (4000-100 cm(-1)) of the molecule in the solid phase were recorded. Theoretical vibrational frequencies and geometric parameters (bond lengths, bond angles) were calculated using Ab Initio Hartree Fock (HF), Density Functional Theory (B3LYP) methods with 6-311++G(d,p) basis set by Gaussian 09W program. The computed values of frequencies are scaled using a suitable scale factor to yield good coherence with the observed values. The assignments of the vibrational frequencies were performed by potential energy distribution (PED) analysis by using VEDA 4 program. The theoretical optimized geometric parameters and vibrational frequencies were compared with the corresponding experimental X-ray diffraction data, and they were seen to be in a good agreement with each other. Also, the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) energies were calculated.


Subject(s)
Amides/chemistry , Pyrazoles/chemistry , Biphenyl Compounds/chemistry , Butanols/chemistry , Crystallography, X-Ray , Models, Molecular , Spectrum Analysis
16.
Eurasian J Med ; 46(1): 61-3, 2014 Feb.
Article in English | MEDLINE | ID: mdl-25610298

ABSTRACT

Hypertrophic column of Bertin (HCB) may mimic renal mass and may lead to unnecessary nephrectomy in some conditions. In this case report we present a patient with HCB, which mimics renal mass in ultrasonography (US) examination with its US, Doppler US and magnetic resonance imaging (MRI) findings. In contrast to the US, excretory urography (EU) and computed tomography (CT) findings of HCB, MRI findings of this entity could not take part in the literature sufficiently. We suggest that this case report could be useful in preventing the unnecessary biopsy and surgical procedures. In conclusion, however, US is often sufficient in the diagnosis of HCB, unusual lesions could be seen. In the final diagnosis of these lesions, MRI is very useful and more responsive technique. Understanding the imaging characteristics of HCB could prevent unnecessary interventional or surgical procedures.

17.
Can Urol Assoc J ; 7(9-10): E605-8, 2013.
Article in English | MEDLINE | ID: mdl-24069106

ABSTRACT

We report a very unusual complication of uretero-iliac artery fistula that developed following robotic radical cystectomy (RARC), bilateral extended pelvic lymph node dissection and intracorporeal Studer pouch reconstruction. Our patient was a 54-year-old male who was admitted 1 month after undergoing robotic surgery due to intermittently occurring massive transurethral bleeding necessitating blood transfusion that stopped by itself. Angiography showed a right external iliac artery pseudo-aneurysm and a fistula tract between the pseudo-aneurysm and Wallace type ureteral anostomosis that was successfully treated by an angiographic endovascular stent insertion at this level. Uretero-iliac artery fistula might occur following RARC, bilateral extended pelvic lymph node dissection and intracorporeal Studer pouch reconstruction leading to intermittently massive transurethral bleeding. Angiography and stenting are important for diagnosis and successful treatment of this rare entity.

19.
Clin Appl Thromb Hemost ; 18(2): 206-10, 2012.
Article in English | MEDLINE | ID: mdl-21949034

ABSTRACT

BACKGROUND: Extensive research has been performed regarding the association between platelet activity indices and various cardiovascular disorders. Less clear data, however, are present between these indices and deep vein thrombosis (DVT). AIM: The aim of this study was to investigate the association between platelet activity indices and DVT in a relatively large population. METHODS: Mean platelet volume (MPV), mean platelet mass (MPM), and mean platelet component (MPC) were measured by an autoanalyzer in a total of 203 patients with DVT and the results were compared with 210 age- and sex-matched controls without DVT. RESULTS: There were significant differences between the study and control groups in MPV (8.6 ± 1.3 fL vs 7.9 ± 0.5 fL [95% CI -0.82 to -0.44], P < .001, respectively), MPM (2.2 ± 0.3 pg vs 2.0 ± 0.1 pg [95% CI -0.20 to -0.11], P < .001, respectively), and MPC (24.9 ± 3.2 g/dL vs 26.3 ± 1.6 g/dL [95% CI 0.91 to 1.89], P < .001, respectively). These 3 platelet activity indices were also found to be significant predictors of the presence of DVT (all Ps < .001). CONCLUSION: In patients with DVT, the presence of DVT was closely associated with increased platelet activation. The MPV, MPM, and MPC may identify patients requiring aggressive antiplatelet treatment.


Subject(s)
Blood Platelets/physiology , Platelet Activation , Thrombophlebitis/blood , Adult , Aged , Blood Glucose/analysis , Blood Platelets/ultrastructure , Cell Size , Comorbidity , Diabetes Complications/blood , Female , Humans , Hypertension/blood , Lipids/blood , Male , Middle Aged , Platelet Count , Platelet Function Tests/instrumentation , Platelet Function Tests/methods , Smoking/blood , Thrombophlebitis/diagnostic imaging , Ultrasonography, Doppler, Duplex
20.
Diagn Interv Radiol ; 18(1): 102-5, 2012.
Article in English | MEDLINE | ID: mdl-21516611

ABSTRACT

PURPOSE: To compare 21 and 27 gauge (G) needles used for fine-needle aspiration (FNA) of thyroid nodules to obtain better specimens for adequacy and cytological diagnosis. MATERIALS AND METHODS: One hundred patients with thyroid nodules (100 nodules) were included in this study. Each nodule was aspirated with both 27 G and 21 G needles. The obtained aspirates were classified as adequate and inadequate by two separate cytopathologists. The results were analyzed by appropriate statistical methods. RESULTS: There was no statistically significant difference between 21 G and 27 G needles in terms of adequacy, according to each pathologist (P > 0.05). After pathological evaluation with consensus, the adequacy prevalence was the same (84%) for both needle types in all study populations (P > 0.05). According to the ultrasound characteristics of nodules, the prevalence of inadequate samples in patients with hypoechoic or heterogeneous nodules was significantly higher compared with the prevalence of inadequate samples in patients with isoechoic or hyperechoic nodules for both types of needles (P < 0.05). However, according to the size of the needles, there was no significant difference between hypoechoic and heterogeneous nodules or between isoechoic and hyperechoic nodules with regard to the ability to yield adequate samples (P > 0.05). CONCLUSION: The results of our study showed that FNA with 27 G needles can aspirate adequate material for cytopathological diagnosis. The probability of inadequate sample aspiration of hypoechoic and heterogeneous nodules is higher than that for other nodule types.


Subject(s)
Biopsy, Fine-Needle/instrumentation , Needles , Thyroid Nodule/pathology , Adult , Aged , Equipment Design , Female , Humans , Male , Middle Aged
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