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Medicinal Chemistry Research

Gurleen K Samra, Kenneth Dang, Heather Ho, Aparna Baranwal, Jogeshwar Mukherjee
Alzheimer's disease (AD) affects 10% of people older than 65 and is characterized by a progressive loss of cognitive function with an abnormal accumulation of amyloid β (Aβ ) plaques and neurofibrillary tangles (NFT) in the brain. Efforts to reduce brain Aβ plaques continue to be investigated as a therapeutic approach for AD. We report here development of dual targeting agents with affinity for Aβ plaque/P-glycoprotein (Pgp) and Aβ plaque/α4β 2* nicotinic acetylcholine receptors (nAChR). These novel dual agents may be able to efflux Aβ plaques via the paravascular (glymphatic) pathways...
June 2018: Medicinal Chemistry Research
Alicja Kowalska, Krystian Pluta, Małgorzata Latocha
A synthesis of new 2,6-disubstituted and 2,6,8-trisubstituted 7-methylpurines as well as 8-substituted 3,7-dimethylxanthines containing a triple bond chain have been worked out. Purinethiones and xanthinethiones were converted into propynylthio derivatives, which were then further transformed via a Mannich reaction into aminobutynylthio derivatives (amine = pyrrolidine, piperidine, morpholine, and diethylamine). The products thus obtained represent various types of the purine and xanthine structure: 8-mono-, 2,6- and 6,8-dipropynylthio, 6- and 8-monoaminobutynylthio, 2,6- and 6,8-diaminobutynylthio derivatives...
2018: Medicinal Chemistry Research
Agnieszka A Kaczor, Justyna Żuk, Dariusz Matosiuk
The dopaminergic hypothesis of schizophrenia is the main concept explaining the direct reasons of schizophrenia and the effectiveness of current antipsychotics. All antipsychotics present on the market are potent dopamine D2 receptor antagonists or partial agonists. In this work we investigate a series of dopamine D2 receptor antagonists which do not fulfill the criteria of the classical pharmacophore model as they do not possess a protonatable nitrogen atom necessary to interact with the conserved Asp(3.32)...
2018: Medicinal Chemistry Research
Krzysztof Z Łączkowski, Joanna Anusiak, Marta Świtalska, Katarzyna Dzitko, Joanna Cytarska, Angelika Baranowska-Łączkowska, Tomasz Plech, Agata Paneth, Joanna Wietrzyk, Joanna Białczyk
Synthesis, characterization, and investigation of antiproliferative activities against human cancer cell lines (MV4-11, MCF-7, and A549) and Toxoplasma gondii parasite of twelve novel 2,4-diaminotriazine-thiazoles are presented. The toxicity of the compounds was studied at three different cell types, normal mouse fibroblast (Balb/3T3), mouse fibroblast (L929), and human VERO cells. The structures of novel compounds were determined using 1 H and 13 C NMR, FAB(+)-MS, and elemental analyses. Among the derivatives, 4a - k showed very high activity against MV4-11 cell line with IC50 values between 1...
2018: Medicinal Chemistry Research
Alex G Baldwin, Jonathan Bevan, David Brough, Ruth Ledder, Sally Freeman
Dehydroacetic acid is a common pyrone derivative used commercially as an antibacterial and antifungal agent. Based on the synthesis of dehydroacetic acid ( 1 ) from N -hydroxysuccinimdyl acetoacetate, a novel series of enamine-based derivatives were synthesised in order to improve the antibacterial activity of dehydroacetic acid. The antibacterial activities of the synthesised analogues were evaluated against Escherichia coli and Staphylococcus aureus . Derivative 4d (N-Ph) was identified as the most potent inhibitor of S...
2018: Medicinal Chemistry Research
Katarzyna Sidoryk, Marta Świtalska, Piotr Rózga, Joanna Wietrzyk, Iwona Bujak, Bartłomiej Żerek, Łukasz Kaczmarek, Marcin Cybulski
An optimization of the guanidylation process by verifying the efficacy of common guanylation reagents in order to obtain the guanidine derivatives of indolo[2,3-b]quinoline has been performed. As a result, a high-yield procedure using N , N '-di-Boc- N ''-triflylguanidine was applied to synthesize the guanidine derivative of indolo[2,3-b]quinoline 1 in a gram scale for specific in vitro and in vivo biological research. Extensive studies on the antiproliferative activity against eight human tumor cell lines were completed...
2017: Medicinal Chemistry Research
Bini Mathew, Judith V Hobrath, Wenyan Lu, Yonghe Li, Robert C Reynolds
As part of an ongoing program to study the anticancer activity of non-steroidal anti-inflammatory drugs (NSAIDs) through generating diversity libraries of multiple NSAID scaffolds, we synthesized a series of NSAID amide derivatives and screened these sets against three cancer cell lines (prostate, colon and breast) and Wnt/β-catenin signaling. The evaluated amide analog libraries show significant anticancer activity/cell proliferation inhibition, and specific members of the sets show inhibition of Wnt/β-catenin signaling...
2017: Medicinal Chemistry Research
Agnieszka Sobczak, Artur Teżyk, Joanna Szyndlarewicz, Jan Ziarniak, Piotr Świątek, Wiesław Malinka
Hydrochloride of 10-{2-hydroxy-3-[ N , N -bis-(2-hydroxyethyl)amino]propyl}-2-trifluoromethylphenothiazine (Flu-A) is a analogue of neuroleptic fluphenazine. Flu-A exhibits anti-multidrug resistance, antimutagenic, proapoptopic, and cancer-chemopreventive activities in screening studies. To define identity, quality, and purity of new active substance it is necessary to develop a appropriate analytical method and to establish a degradation profile. Thus, a stability-indicating reversed-phase high-performance liquid chromatography method was developed and validated for quantitative determination of Flu-A in the presence of its degradation products generated under stress conditions...
2017: Medicinal Chemistry Research
Waldemar Tejchman, Izabela Korona-Glowniak, Anna Malm, Marek Zylewski, Piotr Suder
A series of rhodanine 3-carboxyalkanoic acid derivatives possessing 4'-(N,N-dialkyl-amino or diphenylamino)-benzylidene moiety as a substituent at the C-5 position were synthesised and their antibacterial activity was screened. All the rhodanine derivatives showed bacteriostatic or bactericidal activity to the reference gram-positive bacterial strains, but lack of activity to the reference Gram-negative bacterial strains and yeast strains was observed.
2017: Medicinal Chemistry Research
Magdalena Jurzak, Paweł Ramos, Barbara Pilawa
Normal and keloid fibroblasts were examined using X-band (9.3 GHz) electron paramagnetic resonance spectroscopy. The effect of genistein on the concentration of free radicals in both normal dermal and keloid fibroblasts after ultraviolet irradiation was investigated. The highest concentration of free radicals was seen in keloid fibroblasts, with normal fibroblasts containing a lower concentration. The concentration of free radicals in both normal and keloid fibroblasts was altered in a concentration-dependent manner by the presence of genistein...
2017: Medicinal Chemistry Research
Łukasz Popiołek
Hydrazide-hydrazone derivatives are present in many bioactive molecules and display a wide variety of biological activities, such as antibacterial, antitubercular, antifungal, anticancer, anti-inflammatory, anticonvulsant, antiviral, and antiprotozoal action. Therefore, many medicinal chemists synthesize various hydrazide-hydrazones and evaluate them for biological activities. Among biological properties of this class of compounds, antimicrobial activity is the most frequently encountered in scientific literature...
2017: Medicinal Chemistry Research
Agata Antosiak, Katarzyna Milowska, Katarzyna Maczynska, Sylwia Rozalska, Teresa Gabryelak
Genistein belongs to isoflavones, which are a subclass of flavonoids, a large group of polyphenolic compounds widely distributed in plants. Numerous in vitro studies suggest that isoflavones, particularly genistein, have both chemopreventive and chemotherapeutic potential in multiple tumor types. However, the molecular and cellular mechanisms of genistein effects on human ovarian cancer cells are still little known. In the present study, we investigated anticancer activity of genistein and its natural glucoside, genistein-8-C-glucoside isolated from flowers of Lupinus luteus L...
2017: Medicinal Chemistry Research
Ewa Bębenek, Monika Kadela-Tomanek, Elwira Chrobak, Joanna Wietrzyk, Joanna Sadowska, Stanisław Boryczka
Betulin 1 and its semisynthetic derivatives exhibit a cytotoxic activity toward various cancer cell lines. These compounds are a promising and potential anticancer candidates. A series of betulin derivatives was prepared and tested for the antiproliferative activity in vitro against T47D breast cancer, CCRF/CEM leukemia, HL-60 promyelocytic leukemia, SW707 colorectal, murine P388 leukemia, as well as BALB3T3 normal fibroblasts cell lines. Cisplatin and betulin 1 were used as a reference compounds. Some derivatives of betulin showed a higher cytotoxic activity than the parent compound 1...
2017: Medicinal Chemistry Research
Ying Gao, Shane A Snyder, Jaclyn N Smith, Yi Charlie Chen
The constituents of many traditional Chinese herbal remedies are currently at the forefront of modern cancer research. Baicalein, a bioactive flavone widely used in nutraceuticals and pharmaceuticals, has shown great potential in the treatment and prevention of cancer without causing severe side effects. Baicalein induces cancer cell apoptosis and cause cell cycle arrest. It shows inhibitory effects on angiogenesis, metastasis and inflammation, all of which are necessary for the promotion and progression of cancer...
August 2016: Medicinal Chemistry Research
Hyo Sang Jo, Hyun Ju Cha, Sang Jin Kim, Hyeon Ji Yeo, Su Bin Cho, Jung Hwan Park, Chi Hern Lee, Eun Ji Yeo, Yeon Joo Choi, Won Sik Eum, Soo Young Choi
Oxidative stress is highly involved in the development of diabetes mellitus by destruction of pancreatic β-cells. DJ-1 is an antioxidant protein and DJ-1 expression levels are known to be reduced in diabetes mellitus. Thus, we examined the effects of DJ-1 protein against oxidative stress-induced pancreatic β-cell (RINm5F) death using cell permeable wild-type and mutant-type (C106A) Tat-DJ-1 proteins, which both efficiently transduced into RINm5F cells. Intracellular stability of wild-type Tat-DJ-1 persisted two times longer than C106A Tat-DJ-1...
2016: Medicinal Chemistry Research
Beata Morak-Młodawska, Krystian Pluta, Małgorzata Latocha, Małgorzata Jeleń
New phenothiazine derivatives as 10-substituted dipyridothiazines of the 1,6-diazaphenothiazine structure were obtained in the cyclization reaction of 3-amino-3'-nitro-2,2'-dipyridinyl sulfide and 3,3'-dinitro-2,2'-dipyridinyl disulfide, and in the reaction of 2-chloro-3-ntropyridine with sodium 3-amino-2-pyridinethiolate followed by various alkylation and arylation reactions. The reaction of the thiazine ring formation ran via the Smiles rearrangement of the S-N type. As the alkylation reactions could proceed at the thiazine, azine or both nitrogen atoms, the product structure elucidation was based on the 2D NMR (Rotating-frame Overhauser Effect Spectroscopy, Correlated Spectroscopy, Heteronuclear Single Quantum Coherence, and Heteronuclear Multiple Bond Correlation) spectra of the N-methylated product...
2016: 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
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