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Medicinal Chemistry Research

Monika Pitucha, Maciej Woś, Malgorzata Miazga-Karska, Katarzyna Klimek, Barbara Mirosław, Anna Pachuta-Stec, Agata Gładysz, Grazyna Ginalska
In this study, the antibacterial, cytotoxic and antiproliferative activities of novel thiosemicarbazide derivatives were assessed. Our results demonstrated that some of the novel compounds possess good antibacterial properties against Staphylococcus epidermidis, Streptococcus mutans and Streptococcus sanguinis and are only slightly cytotoxic; thus, they exhibit an excellent therapeutic index, which is higher than that of ethacridine lactate. Moreover, our data showed that compounds 2 and 4 have an antiproliferative activity against human breast adenocarcinoma and human hepatocellular carcinoma cell lines...
2016: Medicinal Chemistry Research
Faraz Shaikh, Shirley W I Siu
ABSTRACT: Neuropathic pain and inflammatory pain are two common types of pathological pain in human health problems. To date, normal painkillers are only partially effective in treating such pain, leading to a tremendous demand to develop new chemical entities to combat pain and inflammation. A promising pharmacological treatment is to control signal transduction via the inflammatory mediator-coupled receptor protein C5aR by finding antagonists to inhibit C5aR activation. Here, we report the first computational study on the identification of non-peptide natural compound inhibitors for C5aR by homology modeling and virtual screening...
2016: Medicinal Chemistry Research
Brian D Wright, Michael C Deblock, Patrick O Wagers, Ernest Duah, Nikki K Robishaw, Kerri L Shelton, Marie R Southerland, Michael A DeBord, Kortney M Kersten, Lucas J McDonald, Jason A Stiel, Matthew J Panzner, Claire A Tessier, Sailaja Paruchuri, Wiley J Youngs
The anti-tumor activity of imidazolium salts is highly dependent upon the substituents on the nitrogen atoms of the imidazolium cation. We have synthesized and characterized a series of naphthalene-substituted imidazolium salts and tested them against a variety of non-smallcell lung cancer cell lines. Several of these complexes displayed anticancer activity comparable to cisplatin. These compounds induced apoptosis in the NCI-H460 cell line as determined by Annexin V staining, caspase-3, and PARP cleavage. These results strongly suggest that this class of compounds can serve as potent chemotherapeutic agents...
July 2015: Medicinal Chemistry Research
Nelly Mateeva, Madhavi Gangapuram, Elizabeth Mazzio, Suresh Eyunni, Karam F A Soliman, Kinfe K Redda
Flavonoids and chalcones are natural plant derived compounds with inherent therapeutic value for a range of human pathologies. In this study, a series of 24 substituted chalcones and flavones were synthesized and subsequently screened for anti-inflammatory effects on lipopolysaccharide (1 µg/ml)-activated BV-2 microglial cells by assessing initial production/release of nitric oxide (NO). The data obtained eliminate the majority of compounds as weak or non-effective, whereas 2'-hydroxy-3,4,5,3',4'-pentamethoxychalcone (1) and 2'-hydroxy-3,4,5-trimethoxychalcone (2) were potent, having an IC50 of 1...
April 2015: Medicinal Chemistry Research
Joanne P Thio, Christopher Liang, Alisha K Bajwa, Dustin W Wooten, Bradley T Christian, Jogeshwar Mukherjee
(18)F-Mefway (N-{2-[4-(2'-methoxyphenyl)piperazinyl]ethyl}-N-(2-pyridyl)-N-(4'-(18)F-fluoro-methylcyclohexane)carboxamide) was developed and evaluated for use as a PET ligand for imaging 5-HT1A receptors. Ongoing studies of (18)F-Mefway have shown it to be an effective PET radiotracer. We have synthesized isomers of Mefway by changing the position of the methyl-group in attempts to evaluate stability for imaging purposes. 2-Methyl-, 3-methyl-, and 4-methyl-cyclohexane-1-carboxylic acids and 3-carbomethoxy-, 4-carbomethoxycyclohexane-1-carboxylic acids were coupled with WAY-100634 to provide the methylcyclohexyl derivatives (2-, 3- and 4-methyl)...
April 2015: Medicinal Chemistry Research
Agata Goszczyńska, Halina Kwiecień, Karol Fijałkowski
A series of novel Schiff bases and secondary amines were obtained in good yields, as a result of the reductive amination of alkyl 2-(2-formyl-4-nitrophenoxy)alkanoates with both aniline and 4-methoxyaniline under established mild reaction conditions. Sodium triacetoxyborohydride as well as hydrogen in the presence of palladium on carbon were used as efficient reducing agents of the Schiff bases, in both direct and stepwise reductive amination processes. The Schiff bases, amines, and amine hydrochlorides were designed as potential antibacterial agents, and structure-activity relationship could be established following in vitro assays against Gram-positive and Gram-negative bacteria...
2015: Medicinal Chemistry Research
Maciej Makowski, Paweł Lenartowicz, Bartosz Oszywa, Michał Jewgiński, Małgorzata Pawełczak, Paweł Kafarski
The procedures for the synthesis of esters of dehydropeptides containing C-terminal (Z)-dehydrophenylalanine and dehydroalanine have been elaborated. These esters appeared to be moderate or weak inhibitors of cathepsin C, with some of them exhibiting slow-binding behavior. As shown by molecular modeling, they are rather bound at the surface of the enzyme and are not submersed in its binding cavities.
2015: Medicinal Chemistry Research
Alicja Kowalska, Małgorzata Latocha, Krystian Pluta
New thiopurines with the propargylthio, pyrrolidinobutynylthio, sulfenamide, and sulfonamide groups in the pyrimidine ring were synthesized. The anticancer activity of these compounds and previously obtained 2- or 6-substituted azathioprine analogs and dialkylaminoalkylthiopurines were tested in vitro against three cell lines: glioblastoma SNB-19, melanoma C-32, and human ductal breast epithelial tumor T47D. 2-Chloro-7-methyl-6-pyrrolidinobutynylthiopurine (5b) was the most potent compound against SBN-19 and C-32 cell lines with the activity similar to cisplatin (EC50 = 5...
2015: Medicinal Chemistry Research
Krzysztof Kamiński, Beata Wiklik, Jolanta Obniska
Twenty-two new N-phenyl-2-(4-phenylpiperazin-1-yl)acetamide derivatives have been synthesized and evaluated for their anticonvulsant activity in animal models of epilepsy. These molecules have been designed as analogs of previously obtained anticonvulsant active pyrrolidine-2,5-diones in which heterocyclic imide ring has been changed into chain amide bound. The final compounds were synthesized in the alkylation reaction of the corresponding amines with the previously obtained alkylating reagents 2-chloro-1-(3-chlorophenyl)ethanone (1) or 2-chloro-1-[3-(trifluoromethyl)phenyl]ethanone (2)...
2015: Medicinal Chemistry Research
Adam Ząbek, Justyna Nagaj, Agnieszka Grabowiecka, Ewa Dworniczek, Urszula Nawrot, Piotr Młynarz, Małgorzata Jeżowska-Bojczuk
Candida species, although they are present as commensal organisms in the digestive tract of healthy individuals, can produce a broad spectrum of serious illnesses in compromised hosts. Fluconazole, a water-soluble triazole with bioavailability greater than 90 %, has been extensively used to treat a wide range of Candida infections. However, a growing resistance of microorganisms in the treatment leads to the discovery of new drugs or modifications of existing ones. The aim of the present study was to investigate whether coordination of Cu(II) ions to fluconazole affects its antifungal activity...
2015: Medicinal Chemistry Research
Małgorzata Jeleń, Eugenia I Bavavea, Maria Pappa, Angeliki P Kourounakis, Beata Morak-Młodawska, Krystian Pluta
New tetracyclic and pentacyclic azaphenothiazines containing one or two quinoline rings instead of benzene rings were obtained in the original reactions of isomeric diquinodithiins, dichlorodiquinolinyl sulfides, and disulfide with aromatic amines. The type of ring fusion in the azaphenothiazine system was concluded from the (1)H NMR spectra. The obtained azaphenothiazines were evaluated in vitro for their antioxidant activity on rat hepatic microsomal membranes for protection of non-enzymatic lipid peroxidation promoted by the Fe(2+)/ascorbic acid redox system...
2015: Medicinal Chemistry Research
Beata Morak-Młodawska, Krystian Pluta, Michał Zimecki, Małgorzata Jeleń, Jolanta Artym, Maja Kocięba
A new type of tricyclic azaphenothiazines-1,8-diazaphenothiazines-was obtained in the reaction of 2,3- and 3,4-disubstituted pyridines. The reaction ran as the Smiles rearrangement. The 1,8-diazaphenothiazine system was determined using NOE experiment and 2D NMR spectra (COSY, HSQC, HMBC). 10H-1,8-diazaphenothiazine was transformed into 10-derivatives with alkyl, aminoalkyl, amidoalkyl, sulfonamidoalkyl, and nitrogen half-mustard groups. The compounds were tested for their effects on phytohemagglutinin A-induced proliferative response of human peripheral blood mononuclear cells (PBMC) and lipopolysaccharide-induced tumor necrosis factor alpha production by human whole blood cultures...
2015: Medicinal Chemistry Research
Agnieszka A Kaczor, Tomasz Wróbel, Christiane Kronbach, Klaus Unverferth, Tomasz Stachal, Dariusz Matosiuk
Here we present the synthesis, pharmacological activity, and molecular docking of novel non-competitive antagonists of GluK2 receptor. The compounds concerned are derivatives of indole and carbazole and are the second reported series of non-competitive antagonists of the GluK2 receptor (the first one was also published by our group). The activity of the indole derivatives is in the micromolar range, as in the case of the first series of non-competitive GluK2 receptor antagonists. We have found that designed carbazole derivatives are devoid of activity...
2015: Medicinal Chemistry Research
Paweł Ramos, Barbara Pilawa
The effect of UVA (315-400 nm) irradiation on Echinaceae purpureae interactions with free radicals was examined by the use of electron paramagnetic resonance (EPR) spectroscopy. The changes of antioxidant properties of E. purpureae with time of UV irradiation from 10 to 110 min (10 min steps) were determined. DPPH as the paramagnetic reference was used in this study. Changes of EPR signals of the reference after interactions with nonirradiated and UV-irradiated E. purpureae were detected. Interactions of the tested E...
2015: Medicinal Chemistry Research
Piotr Kawczak, Leszek Bober, Tomasz Bączek
Thirty-three compounds belonging to the sympatholytics and sympathomimetics were analyzed during the study. The biological activity data for the parameters of binding affinity to the α1- and α2-adrenergic receptors together with parameters of the logarithm of the partition coefficient n-octanol/water (log P) were performed using a semi-empirical calculations methods for isolated molecules (in vacuo) and for the molecules placed in an aqueous environment. Additionally, the chromatographic retention data were used as extra dependent variables of the structural parameters for a part of the considered compounds...
2015: Medicinal Chemistry Research
Justyna Nagaj, Paulina Kołkowska, Aleksandra Bykowska, Urszula K Komarnicka, Agnieszka Kyzioł, Małgorzata Jeżowska-Bojczuk
The acid-base properties and the Cu(II) binding processes of methotrexate (MTX) were characterized by selected spectroscopic techniques and potentiometric measurements. The pH titration data showed that MTX behaves as a triprotic ligand. The deprotonation constants were determined for α-COOH and γ-COOH groups and (N1)H(+) from the pteridine ring. Taking all the obtained results into consideration, a coordination pattern was proposed. The DNA-cleaving activity and reactive oxygen species (ROS) generation were investigated for both MTX and the Cu(II)-MTX system...
2015: Medicinal Chemistry Research
Liu Yang, Xiang Nan, Wen-Qun Li, Mei-Juan Wang, Xiao-Bo Zhao, Ying-Qian Liu, Zhi-Jun Zhang, Kuo-Hsiung Lee
A series of novel spin-labeled 4β-[(4-substituted)-1,2,3-triazol-1-yl]podophyllotoxin derivatives (17a-h) were firstly designed and synthesized with significant regioselectivity by employing Cu(I) catalyzed click approach, and evaluated for cytotoxicity against four human tumor cell lines (A-549, DU145, KB, and KBvin). Among them, compound 17h displayed the highest cytotoxic activity against the tumor cell lines tested. Significantly, compound 17h showed superior cytotoxic activity compared with etoposide (IC50 6...
November 2014: Medicinal Chemistry Research
Tarek Aboul-Fadl, Suliman S Al-Hamad, Kevin Lee, Nan Li, Bernard D Gary, Adam B Keeton, Gary A Piazza, Mohammed K Abdel-Hamid
A structure-based medicinal chemistry strategy was applied to design new naproxen derivatives that show growth inhibitory activity against human colon tumor cells through a cyclooxygenase (COX)-independent mechanism. In vitro testing of the synthesized compounds against the human HT-29 colon tumor cell line revealed enhanced growth inhibitory activity compared to the parent naproxen with 3a showing IC50 of 11.4 μM (two orders of magnitude more potent than naproxen). Selectivity of 3a was investigated against a panel of three tumor and one normal colon cell lines and showed up to six times less toxicity against normal colonocytes...
September 2014: Medicinal Chemistry Research
Afeef S Husni, Christopher R McCurdy, Mohamed M Radwan, Safwat A Ahmed, Desmond Slade, Samir A Ross, Mahmoud A ElSohly, Stephen J Cutler
Cannabis has been around for thousands of years and has been used recreationally, medicinally, and for fiber. Over 500 compounds have been isolated from Cannabis sativa with approximately 105 being cannabinoids. Of those 105 compounds, Δ(9)-tetrahydrocannabinol has been determined as the primary constituent, which is also responsible for the psychoactivity associated with Cannabis. Cannabinoid receptors belong to the large superfamily of G protein-coupled receptors. Targeting the cannabinoid receptors has the potential to treat a variety of conditions such as pain, neurodegeneration, appetite, immune function, anxiety, cancer, and others...
September 1, 2014: Medicinal Chemistry Research
Suniti Misra, Shibnath Ghatak, Alok Vyas, Paul O'Brien, Roger R Markwald, Madhukar Khetmalas, Vincent C Hascall, James B McCarthy, Nikos K Karamanos, Markku I Tammi, Raija H Tammi, Glenn D Prestwitch, Subhash Padhye
Inflammatory pathway plays an important role in tumor cell progression of colorectal cancers. Although colon cancer is considered as one of the leading causes of death worldwide, very few drugs are available for its effective treatment. Many studies have examined the effects of specific COX-2 and 5-LOX inhibitors on human colorectal cancer, but the role of isothiocyanates (ITSCs) as COX-LOX dual inhibitors engaged in hyaluronan-CD44 interaction has not been studied. In the present work, we report series of ITSC analogs incorporating bioisosteric thiosemicarbazone moiety...
August 1, 2014: Medicinal Chemistry Research
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