- Hybrid organoruthenium(II) complexes with thiophene-β-diketo-benzazole ligands: Synthesis, optical properties, CT-DNA interactions and anticancer activity
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Two new hybrid half‐sandwiched Ru(II) arene complexes of a general formula [η6-(p-cymene)Ru(L)Cl] (4a,b) {where L = 1-(Benzazol-2-yl)-3-(thiophen-2-yl) propane-1,3-dione} were synthesized and characterized. Spectral and elemental analysis revealed that these complexes have tetrahedral piano stool‐like geometry with a coordination environment composed of two O atoms of ligand, chloride ion, and electron cloud of p‐cymene moiety. The CT-DNA–Ru(II) complexes interactions were evaluated based on absorption and emission titration experiments. The results have shown intercalative modes of interaction between DNA and complexes, with a preferable binding to complex 4b. Based on the in vitro cytotoxicity MTT assay, the complexes exhibit significant inhibitory activity against human breast and lung cancer cells (MCF-7, A549), with lower micromolar IC50 values in comparison to that of clinical drug (cisplatin). In contrast, neither complex shows activity against the normal cell lines (Hela), suggesting that the new hybrid thiophene-β-diketo-benzazole organoruthenium(II) complexes may offer promising safe anticancer agents.
- Alfaifi, Mohammad Y.,El-Sayed, W. N.,Elbehairi, Serag Eldin I.,Elshaarawy, Reda F. M.,Gad, Emad M.,Ismail, Lamia A.
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Read Online
- Comprehensive study on potent and selective carbonic anhydrase inhibitors: Synthesis, bioactivities and molecular modelling studies of 4-(3-(2-arylidenehydrazine-1-carbonyl)-5-(thiophen-2-yl)-1H-pyrazole-1-yl) benzenesulfonamides
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In this research, rational design, synthesis, carbonic anhydrases (CAs) inhibitory effects, and cytotoxicities of the 4-(3-(2-arylidenehydrazine-1-carbonyl)-5-(thiophen-2-yl)-1H-pyrazole-1-yl)benzenesulfonamides 1–20 were reported. Compound 18 (Ki = 7.0 nM) was approximately 127 times more selective cancer-associated hCA IX inhibitor over hCA I, while compound 17 (Ki = 10.6 nM) was 47 times more selective inhibitor of hCA XI over hCA II compared to the acetazolamide. Compounds 11 (CC50 = 5.2 μM) and 20 (CC50 = 1.6 μM) showed comparative tumor-specificity (TS= > 38.5; >128.2) with doxorubicin (TS > 43.0) towards HSC-2 cancer cell line. Western blot analysis demonstrated that 11 induced slightly apoptosis whereas 20 did not induce detectable apoptosis. A preliminary analysis showed that some correlation of tumor-specificity of 1–20 with the chemical descriptors that reflect hydrophobic volume, dipole moment, lowest hydrophilic energy, and topological structure. Molecular docking simulations were applied to the synthesized ligands to elucidate the predicted binding mode and selectivity profiles towards hCA I, hCA II, and hCA IX.
- Yamali, Cem,Sakagami, Hiroshi,Uesawa, Yoshihiro,Kurosaki, Kota,Satoh, Keitaro,Masuda, Yoshiko,Yokose, Satoshi,Ece, Abdulilah,Bua, Silvia,Angeli, Andrea,Supuran, Claudiu T.,Gul, Halise Inci
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Read Online
- Synthesis, characterization, thermal analysis and biological study of new thiophene derivative containing o-aminobenzoic acid ligand and its mn(ii), cu(ii) and co(ii) metal complexes
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New ligand containing 2-(2,4-dioxo-4-thiophen-2-yl-butyrylamino)-benzoic acid (HL) merged moiety was synthesized and characterized by FT-IR, elemental analyses, mass spectra and 1H-NMR spectral. In the present study, the attempts were carried to form comp
- Al-Hazmi, Ghaferah H.,Al-Humaidi, Jehan Y.,Altalhi, Tariq A.,Refat, Moamen S.
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p. 129 - 140
(2021/06/03)
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- Synthesis, Characterization, Enzyme Inhibitory Activity, and Molecular Docking Analysis of a New Series of Thiophene-Based Heterocyclic Compounds
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Abstract: 1-Phenyl-3-(thiophen-2-yl)-1H-pyrazole-5-carboxamide derivatives were designed and evaluated for their in vitro enzyme inhibitory activities against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and glutathione S-transferase (GST).
- Bursal, E.,Cetin, A.,Murahari, M.,Türkan, F.
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p. 598 - 604
(2021/06/02)
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- ISOXAZOLE CARBOXAMIDE COMPOUNDS AND USES THEREOF
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A compound of Formula (I) or or a pharmaceutically acceptable salt thereof, is provided that has been shown to be useful for treating hearing loss or balance disorder: Formula (I) wherein R1 and Y are as defined herein.
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Page/Page column 39
(2020/04/25)
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- Synthesis, biological evaluation and in silico modelling studies of 1,3,5-trisubstituted pyrazoles carrying benzenesulfonamide as potential anticancer agents and selective cancer-associated hCA IX isoenzyme inhibitors
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Inhibition of carbonic anhydrases (CAs, EC 4.2.1.1) has clinical importance for the treatment of several diseases. They participate in crucial regulatory mechanisms for balancing intracellular and extracellular pH of the cells. Among CA isoforms, selectiv
- Yamali, Cem,Gul, Halise Inci,Ece, Abdulilah,Bua, Silvia,Angeli, Andrea,Sakagami, Hiroshi,Sahin, Ertan,Supuran, Claudiu T.
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- INHIBITORS OF SHORT-CHAIN DEHYDROGENASE ACTIVITY FOR PROMOTING NEUROGENESIS AND INHIBITING NERVE CELL DEATH
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A method of promoting neuroprotection in a subject from axonal degeneration, neuronal cell death, and/or glia cell damage after injury, augmenting neuronal signaling underlying learning and memory, stimulating neuronal regeneration after injury, and/or treating a disease, disorder, and/or condition of the nervous system in a subject in need thereof includes administering to the subject a therapeutically effective amount of a 15-PGDH inhibitor.
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Paragraph 00268
(2018/02/27)
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- The First Example of Azole-Fused Cyclic Anhydride Reacting in the Castagnoli-Cushman Way
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Pyrazole-fused cyclic anhydrides have been employed for the first time as the Castagnoli-Cushman reaction partners to produce hitherto unknown 4-oxo-4,5,6,7-tetrahydropyrazolo[1,5- a ]pyrazine-7-carboxylates in remarkably convenient and speedy fashion. At
- Moreau, Ella,Dar'In, Dmitry,Krasavin, Mikhail
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supporting information
p. 890 - 893
(2018/03/06)
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- ISOXAZOLE CARBOXAMIDE COMPOUNDS AND USES THEREOF
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A compound of Formula (I)) or or a pharmaceutically acceptable salt thereof, is provided that has been shown to be useful for treating hearing loss or balance disorder: wherein R1 through R3, and L are as defined herein.
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Paragraph 0133-0134
(2018/10/19)
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- INHIBITORS OF SHORT-CHAIN DEHYDROGENASE ACTIVITY FOR TREATING FIBROSIS
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A method of treating or preventing a fibrotic disease, disorder or condition includes administering to a subject in need of treatment a 15-PGDH inhibitor.
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Paragraph 00279
(2016/09/26)
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- COMPOSITIONS AND METHODS OF MODULATING SHORT-CHAIN DEHYDROGENASE ACTIVITY
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Compounds and methods of modulating 15-PGDH activity, modulating tissue prostaglandin levels, treating disease, diseases disorders, or conditions in which it is desired to modulate 15-PGDH activity and/or prostaglandin levels include 15-PGDH inhibitors described herein.
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Paragraph 00473
(2015/05/19)
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- Synthesis and spectroscopic studies of Mn(II), Co(II), and Cu(II) complexes of novel 2-[2,4-Dioxo-4-(thiophen-2-yl)butanamido]benzoic acid ligands
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Mn(II), Co(II), and Cu(II) complexes with novel heterocyclic ligands derived from anthranilic acid and its 5-bromo derivative with ethyl-2-thionylpyruvate were synthesized and characterized by means of elemental analysis, molar conductivity, spectral meth
- Refat, Moamen S.,El-Deen, Ibrahim M.,El-Shaarawy, Reda F. M.
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p. 593 - 601
(2014/05/20)
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- AZAINDAZOLES
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Herein are disclosed azaindazoles of formula (I), (I), where the various groups are defined herein, and which are useful for treating cancer.
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Page/Page column 169-170; 171
(2013/03/28)
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- Synthesis and evaluation as antitubercular agents of 5-arylethenyl and 5-(hetero)aryl-3-isoxazolecarboxylate
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Preclinical Research A new series of 5-aryl and 5-arylethenylisoxazole carboxylate derivatives was synthesized and evaluated for in vitro activity against Mycobacterium tuberculosis H37Rv. Several compounds exhibited minimum inhibitory concentrations in the low micromolar range (2.3-11.4 μM). A variety of substituents introduced around the isoxazole ring allowed the delineation of preliminary SARs for this new series of compounds.
- Vergelli, Claudia,Cilibrizzi, Agostino,Crocetti, Letizia,Graziano, Alessia,Dal Piaz, Vittorio,Wan, Baojie,Wang, Yuehong,Franzblau, Scott,Giovannoni, Maria Paola
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p. 162 - 172
(2013/05/22)
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- Molecular recognition at the active site of factor Xa: Cation-π Interactions, stacking on planar peptide surfaces, and replacement of structural water
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Factor Xa, a serine protease from the blood coagulation cascade, is an ideal enzyme for molecular recognition studies, as its active site is highly shape-persistent and features distinct, concave sub-pockets. We developed a family of non-peptidic, small-molecule inhibitors with a central tricyclic core orienting a neutral heterocyclic substituent into the S1 pocket and a quaternary ammonium ion into the aromatic box in the S4 pocket. The substituents were systematically varied to investigate cation-π interactions in the S4 pocket, optimal heterocyclic stacking on the flat peptide walls lining the S1 pocket, and potential water replacements in both the S1 and the S4 pockets. Structure-activity relationships were established to reveal and quantify contributions to the binding free enthalpy, resulting from single-atom replacements or positional changes in the ligands. A series of high-affinity ligands with inhibitory constants down to Ki=2nM were obtained and their proposed binding geometries confirmed by X-ray co-crystal structures of protein-ligand complexes. Factor Xa is an ideal enzyme to undertake molecular recognition studies at atomic level resolution as its active site is completely conserved in complexes with designed ligands. Cation-π interactions, water replacements, and stacking interactions with flat peptide fragments were investigated, revealing large changes in binding affinity resulting from single-atom mutations or positional shifts of heteroatoms in the ligands. Copyright
- Salonen, Laura M.,Holland, Mareike C.,Kaib, Philip S. J.,Haap, Wolfgang,Benz, J?rg,Mary, Jean-Luc,Kuster, Olivier,Schweizer, W. Bernd,Banner, David W.,Diederich, Fran?ois
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p. 213 - 222
(2012/03/09)
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- Novel 6-N-arylcarboxamidopyrazolo[4,3-d]pyrimidin-7-one derivatives as potential anti-cancer agents
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A novel series of 3,5,6-trisubstituted pyrazolo[4,3-d]pyrimidin-7-one derivatives, especially 6-N-arylcarboxamidopyrazolo[4,3-d]pyrimidin-7-ones were synthesized and evaluated for their in vitro anticancer activities against various human cancer cell line
- Devegowda, Vani N.,Kim, Jung Hyun,Han, Ki-Cheol,Yang, Eun Gyeong,Choo, Hyunah,Pae, Ae Nim,Nam, Ghilsoo,Choi, Kyung Il
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scheme or table
p. 1630 - 1633
(2010/06/19)
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- Synthesis and characterization of some new heterocycles incorporating the 1-Phenyl-5-(2-thienyl)pyrazole moiety
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1-Phenyl-3-(2-thienyl)-1H-pyrazole-5-carbohydrazide 4 was prepared from 2-acetylthio- phene by reaction with diethyl oxalate and phenylhydrazine followed by hydrazine hydrate. The reaction of the hydrazide 4 with phthalic anhydride, aromatic aldehydes, and alkene derivatives gave imide 5, hydrazones 6a-d, and bis-pyrazoles 7 and 8, respectively, while its reaction with phenyl isothiocyanate led to thiosemicarbazide 9. The reaction of the latter with ethyl bromoacetate and phenacylbromide afforded 4-thiazolidinone 10 and 1,3-thiazole 11 derivatives, respectively. Reaction of 4 with carbon disulfide in the presence of potassium hydroxide gave potassium hydrazinecarbodithioate derivative 12, which was used as a starting material in the preparation of 2-thioxothiazol-3(2H)-yl)-5-(2-thienyl)-1H-pyrazole-3-carboxamide 14; 1,3,4-thiadiazol-2(3H)-ylidene)-1-phenyl-5-(2-thienyl)-1H-pyrazole-3- carbohydrazides 16a-c; 4-amino-5-thioxo-4,5-dihydro-1H-1,2,4-triazol-3-yl) pyrazole derivative 13; Schiff bases 17a,b; and 1,2,4-triazolo[3,4-b][1,3,4] thiadiazine derivatives 18 and 19a-e.
- Abdel-Wahab, Bakr F.,El-Ahl, Abdel-Aziz Sayed
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scheme or table
p. 249 - 260
(2010/07/03)
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- Potent nonpeptide endothelin antagonists: Synthesis and structure-activity relationships of pyrazole-5-carboxylic acids
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We have previously reported the identification of pyrazole-5-carboxylic acids as a new class of endothelin antagonists from low affinity pyrazol-5-ol ligands, which were obtained by random screening assays.1 We describe herein the synthesis and the structure-activity relationships (SARs) of these pyrazole-5-carboxylic acids with potent ET(A) selective, mixed ET(A)/ET(B) or moderately ET(B) selective antagonist activities. (C) 2000 Elsevier Science Ltd.
- Zhang, Jidong,Didierlaurent, Stanislas,Fortin, Michel,Lefrancois, Dominique,Uridat, Eric,Vevert, Jean Paul
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p. 2575 - 2578
(2007/10/03)
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- Acid pyrazole derivatives, preparation method therefor, use thereof as drugs, novel use therefor, and pharmaceutical compositions containing such derivatives
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The subject of the invention is the products of formula (I): in which one of A and B represents a nitrogen atom and the other one of A and B represents a methine radical, such that: A represents either nitrogen substituted in particular by alkyl,
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