- A novel class for carbonic anhydrases inhibitors and evaluation of their non-zinc binding
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In this study, 23 different imidazole derivatives were synthesized, and the inhibitory properties of these derivatives against carbonic anhydrase I and II isoenzymes were investigated for the first time. The inhibition concentrations of the imidazole derivatives were found to be in the range of 2.89–115.5 nM. Docking studies examined the binding properties of the imidazole derivatives, and the structure–activity relationship is discussed. Theoretical calculations showed that the binding mode of the imidazole ring was non-zinc binding.
- Kuzu, Burak,Tan, Meltem,Gül?in, ?lhami,Menges, Nurettin
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- Structural elucidation, total synthesis, and cytotoxic activity of effphenol A
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A highly substituted phenol derivative, effphenol A (1), was isolated from the deep-sea-derived fungus Trichobotrys effuse FS524. Its complete structural assignment was established through a combination of spectroscopic analysis together with single-crystal X-ray diffraction experiments and further unequivocally confirmed by a biomimetic total synthesis. Structurally, effphenol A possesses a poly-substituted 6-5/6/6 tetracyclic ring system, which represents the first case of such a skeleton found in nature. Furthermore, the cytotoxic activity of effphenol A (1) toward four human cancer cell lines was assayed. This journal is
- Chen, Shanchong,Chen, Yuchan,Dong, Chunmao,Liu, Hongxin,Liu, Zhaoming,Tan, Haibo,Zhang, Weimin,Zhang, Xiao
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p. 9035 - 9038
(2020/11/27)
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- 1-phenyl-2-phenylaminoethyl ketone derivative and medical application
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The invention belongs to the field of pharmaceutical chemicals, and relates to a micromolecular inhibitor of polymyxin drug-resistant protein MCR-1 and application thereof. The invention relates to acompound shown as a formula I, a pharmaceutically accept
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Paragraph 0085; 0086
(2020/04/17)
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- Design, synthesis and biological evaluation of 1-Phenyl-2-(phenylamino) Ethanone Derivatives as Novel MCR-1 Inhibitors
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Polymyxins are considered to be the last-line antibiotics that are used to treat infections caused by multidrug-resistant (MDR) gram-negative bacteria; however, the plasmid-mediated transferable colistin resistance gene (mcr-1) has rendered polymyxins ine
- Lan, Xiu-juan,Yan, Hai-tao,Lin, Feng,Hou, Shi,Li, Chen-chen,Wang, Guang-shu,Sun, Wei,Xiao, Jun-hai,Li, Song
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supporting information
(2019/08/07)
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- Mono- or di-substituted imidazole derivatives for inhibition of acetylcholine and butyrylcholine esterases
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Mono- or di-substituted imidazole derivatives were synthesized using a one-pot, two-step strategy. All imidazole derivatives were tested for AChE and BChE inhibition and showed nanomolar activity similar to that of the test compound donepezil and higher than that of tacrine. Structure activity relationship studies, docking studies to on X-ray crystal structure of AChE with PDB code 1B41, and adsorption, distribution, metabolism, and excretion (ADME) predictions were performed. The synthesized core skeleton was bound to important regions of the active site of AChE such as the peripheral anionic site (PAS), oxyanion hole (OH), and anionic subsite (AS). Selectivity of the reported test compounds was calculated and enzyme kinetic studies revealed that they behave as competitive inhibitors, while two of the test compounds showed noncompetitive inhibitory behavior. ADME predictions revealed that the synthesized molecules might pass through the blood brain barrier and intestinal epithelial barrier and circulate freely in the blood stream without binding to human serum albumin. While the toxicity of one compound on the WS1 (skin fibroblast) cell line was 1790 μM, its toxicity on the SH-SY5Y (neuroblastoma) cell line was 950 μM.
- Kuzu, Burak,Tan, Meltem,Taslimi, Parham,Gül?in, ?lhami,Ta?p?nar, Mehmet,Menges, Nurettin
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p. 187 - 196
(2019/02/06)
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- Magnesium tetrapyrazinoporphyrazines: Tuning of the pKa of red-fluorescent pH indicators
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Magnesium(ii) tetrapyrazinoporphyrazines (TPyzPzs) are excellent red fluorophores (λF ~ 663 nm, ΦF ~ 0.53 in THF). In this work, a series of magnesium(ii) complexes of unsymmetrical TPyzPzs bearing one or two phenol substituents was prepared. Suitable substitutions on the phenolic moiety tuned its pKa in the range of 5.5 to 13. Deprotonation of the phenolic group at higher pH induced a strong donor (phenolate) in the macrocycle that led to pH-dependent quenching of the red fluorescence of these indicators. pH sensing was proved in water solutions after the incorporation of TPyzPzs into two delivery systems-microemulsions and liposomes. The latter also serves as a simple model of biomembranes. Finally, a wavelength-ratiometric probe was constructed by the incorporation of a TPyzPz indicator and lipophilic pH-nonsensitive BODIPY dye into liposomes. Synthetic precursors for TPyzPzs, substituted pyrazine-2,3-dicarbonitriles, also represent donor-acceptor systems and the pH-dependent changes in absorption spectra may be easily visible to the naked eye.
- Karlikova, Martina,Cermakova, Veronika,Demuth, Jiri,Valer, Vojtech,Miletin, Miroslav,Novakova, Veronika,Zimcik, Petr
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supporting information
p. 6162 - 6173
(2019/05/16)
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- Mesogenic heterocycles derived from quinoxaline Schiff Bases
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Three new series of heterocyclic quinoxaline Schiff Bases 1–2 were prepared, characterized and their mesomorphic properties were investigated. These compounds 1 and 2 are in fact geometric isomers in which an imine moiety (e.g., [sbnd]C[dbnd]N) is inversely incorporated into quinoxaline, leading to an opposite local dipole. Two single crystallographic structures 1 (m=8, n=8) and 2a (m=12, n=8) were determined by X-ray crystallographic analysis in order to understand the effect of mesomorphic properties. Weak H-bonds, CH–π and π–π interactions were found in both crystals, which were attributed to the formation of mesomorphic behavior. Variable temperature FT-IR experiments were performed to confirm the induced H-bonds. All series?of compounds 1–2 exhibited N/SmC or SmC phases, which were identified by optical microscope and confirmed by powder X-ray diffraction experiments. Compounds 2a have a slightly wider range of mesophase temperatures than that of compounds 1 and 2b.
- Kuo, Hsiu-Ming,Ko, Wan-Ping,Hsu, Yu-Te,Lee, Gene-Hsiang,Lai, Chung K.
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p. 6321 - 6333
(2016/09/23)
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- Phenyl glyoxal probes
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Novel phenyl-glyoxal based anti-citrulline probes and methods of synthesis are provided. Methods of use, such as, the development of methods for monitoring substrate citrullination over time; for identifying citrullinated proteins from cells are described
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Page/Page column 27
(2016/06/13)
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- Design and synthesis of coumarin-glyoxal hybrids for spermicidal and antimicrobial actions: A dual approach to contraception
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Today there is an urgent need for safe and effective dual-purpose contraceptive agents, which can simultaneously prevent unintended pregnancies and sexually transmitted infections (STI). There are several naturally occurring antimicrobial and antibiotic drugs (novobiocin, coumermycin and chlorobiocin) reported in the literature, which are based on 4-hydroxy coumarins as the active pharmacophore. Based on these interesting reports, we designed and synthesized a library of new 4-hydroxy coumarin derivatives and evaluated them for spermicidal activity. Among the tested compounds, two compounds (2a and 2d) displayed better activity (greater than 95% sperm immobilization at 0.5 mM concentration) than the positive control nonoxynol-9 (N-9). Furthermore, all the compounds were screened for antimicrobial activity against different strains of Trichomonas vaginalis and two compounds (2c and 2h) exhibited potent activity as compared to the reference drug metronidazole. The cytotoxicity assay showed that most of these compounds were safer than the N-9 against the human cervical HeLa cell line and normal vaginal flora Lactobacillus jensenii strains. The studies have demonstrated that compound (2a) is a potential lead to develop a dually active vaginal contraceptive.
- Gupta, Swati,Kushwaha, Bhavana,Srivastava, Akansha,Maikhuri, Jagdamba Prasad,Sankhwar, Satya N.,Gupta, Gopal,Dwivedi, Anil Kumar
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p. 76288 - 76297
(2016/08/30)
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- PYRIDOPYRAZINES AS ANTICANCER AGENTS
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The present invention relates to pyridopyrazine derivatives and solvates, hydrates and pharmaceutically acceptable salts thereof, the use of them in the prevention and/or the treatment of cancer diseases, as well as pharmaceutical compositions containing at least one of them as pharmaceutically active agent(s) together with pharmaceutically acceptable carrier, excipient and/or diluents, especially for the prevention and/or treatment of cancer diseases.˙
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Page/Page column 13
(2014/07/22)
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- Synthesis of 2-aroyl-(4 or 5)-aryl-1H-imidazoles and 2-hydroxy-3,6-diaryl- pyrazines via a cascade process
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The synthesis of (4 or 5)-aryl-2-aroyl-1H-imidazoles and 2-hydroxy-3,6-diarylpyrazines from aryl methyl ketones via a cascade process of DMSO-HBr oxidation and Debus reaction was investigated. Owing to the simple starting materials, mild conditions, easy operation, high bioactivity of imidazole and pyrazine derivatives, this protocol has great potential in medicinal chemistry.
- Liu, Cong,Dai, Rong J.,Yao, Guo W.,Deng, Yu L.
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p. 146 - 163
(2014/04/17)
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- Unexplored reactivity of 2-oxoaldehydes towards Pictet-Spengler conditions: Concise approach to β-carboline based marine natural products
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Novel reactions under Pictet-Spengler conditions between tryptophan methyl ester/tryptamine and 2-oxoaldehydes have been developed and successfully utilized for the total synthesis of Merinacarboline (A and B), Eudistomin Y1, Pityriacitrin B, Pityriacitrin, Fascaplysin and analogues.
- Battini, Narsaiah,Padala, Anil K.,Mupparapu, Nagaraju,Vishwakarma, Ram A.,Ahmed, Qazi Naveed
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p. 26258 - 26263
(2014/07/08)
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- Quinoxaline derivatives: Novel and selective butyrylcholinesterase inhibitors
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Alzheimer's disease (AD) is a progressive brain disorder which occurs due to lower levels of acetylcholine (ACh) neurotransmitters, and results in a gradual decline in memory and other cognitive processes. Acetycholinesterase (AChE) and butyrylcholinesterase (BChE) are considered to be primary regulators of the ACh levels in the brain. Evidence shows that AChE activity decreases in AD, while activity of BChE does not change or even elevate in advanced AD, which suggests a key involvement of BChE in ACh hydrolysis during AD symptoms. Therefore, inhibiting the activity of BChE may be an effective way to control AD associated disorders. In this regard, a series of quinoxaline derivatives 1-17 was synthesized and biologically evaluated against cholinesterases (AChE and BChE) and as well as against achymotrypsin and urease. The compounds 1-17 were found to be selective inhibitors for BChE, as no activity was found against other enzymes. Among the series, compounds 6 (IC50 = 7.7 ± 1.0μM) and 7 (IC50 = 9.7 ± 0.9 μM) were found to be the most active inhibitors against BChE. Their IC50 values are comparable to the standard, galantamine (IC50 = 6.6 ± 0.38 μM). Their considerable BChE inhibitory activity makes them selective candidates for the development of BChE inhibitors. Structure-activity relationship (SAR) of this new class of selective BChE inhibitors has been discussed.
- Zeb, Aurang,Hameed, Abdul,Khan, Latifullah,Khan, Imran,Dalvandi, Kourosh,Choudhary, M. Iqbal,Basha, Fatima Z.
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p. 724 - 729
(2015/04/14)
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- Design and synthesis of 2-acylbenzothiazoles via in situ cross-trapping strategy from benzothiazoles with aryl ketones
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An I2/KOH synergistically promoted direct ring-opening aroylation of benzothiazoles with aryl ketones has been discovered. Aryl ketones were seen to act as carbonyl sources to construct 2-acylbenzothiazoles. This reaction could provide an example for the convergent integration of self-labor domino sequences based on an in situ cross-trapping strategy.
- Gao, Qinghe,Wu, Xia,Jia, Fengcheng,Liu, Meicai,Zhu, Yanping,Cai, Qun,Wu, Anxin
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p. 2792 - 2797
(2013/04/24)
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- I2-promoted direct one-pot synthesis of 2-aryl-3-(pyridine-2- ylamino)imidazo[1,2-a]pyridines from aromatic ketones and 2-aminopyridines
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An I2-promoted one-pot protocol was proposed for the synthesis of 2-aryl-3-(pyridine-2-ylamino)imidazo[1,2-a]pyridines from aromatic ketones and 2-aminopyridines. The present reaction proceeded well in the presence of I2 in DMSO, and it avoided the requirement of any metal, base, and ligand.
- Fei, Zhuan,Zhu, Yan-Ping,Liu, Mei-Cai,Jia, Feng-Cheng,Wu, An-Xin
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supporting information
p. 1222 - 1226
(2013/03/14)
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- A convenient synthesis of novel 2,8-disubstituted pyrido[3,4-b]pyrazines possessing biological activity
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A regioselective synthetic route to 2,8-disubstituted pyrido[3,4-b] pyrazines, by initial condensation reaction between suitable diaminopyridines and α-keto aldehydes equivalents, has been developed. Focusing on the functionalization on C-8, 2-aryl-8-bromo- and 8-amino-2-arylpyrido[3,4-b] pyrazines have been synthesized. Anilines, amides, and ureas have been introduced at the 8-position from key intermediates. 2,8-Disubstituted pyrido[3,4-b]pyrazines thus prepared were found to be of biological interest. Georg Thieme Verlag Stuttgart. New York.
- Antoine, Maud,Gerlach, Matthias,Guenther, Eckhard,Schuster, Tilmann,Czech, Michael,Seipelt, Irene,Marchand, Pascal
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experimental part
p. 69 - 82
(2012/03/27)
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- Synthesis and pharmacological investigation of new arylethanolamines as β3-adrenoceptor ligands
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A series of arylethanolamines with the amino group bearing a variety of bulky alicyclic residues was synthesized. The para position of the benzene ring was variously substituted to further vary lipophilic and steric properties. The meta-chloro substituted derivatives were also considered. Thirteen representative compounds were tested for their ability to displace [3H]CGP 12177 from rat recombinant β3-adrenoceptors and some were found to exhibit activity comparable with that of BRL 37344, chosen as the reference drug. N-Alicyclic substituents can profitably replace the commonly used N-arylalkyl substituents in this class of drugs.
- Grandi, Teresa,Muzzin, Patrick,Giacobino, Jean-Paul,Sparatore, Fabio
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p. 561 - 564
(2007/10/03)
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- Kinetics and mechanism of oxidation of o-, m- and p-hydroxy-acetophenones by hexacyanoferrate(III) in alkaline medium
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Oxidation of o-, p- and m-hydroxyacetophenones by hexacyanoferrate(III) in alkaline medium is first order each in and .Added KCl and increase in increase the rate.Activation parameters have been calculated and
- Gupta, K. C.,Gupta, Renu,Saxena, Usha
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p. 253 - 254
(2007/10/02)
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- 6-(1-ACYL-1-HYDROXYMETHYL)PENICILLANIC ACID DERIVATIVES
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6-(1-Acyl-1-hydroxymethyl)penicillanic acid derivatives are useful as antibacterials and/or beta-lactamase inhibitors.
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- Structure-activity Relationship of Herbicidal 2,3-Dicyano-5-Substituted Pyrazines
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Sixty six 2,3-dicyano-5-substituted pyrazines were synthesized and their herbicidal activities against barnyard grass were measured in pot tests to clarify the relationship between chemical structure and activity.The activity of 59 derivatives was related parabolically to the hydrophobic substituent parameter at the 5-position of the pyrazine ring.
- Nakamura, Akira,Ataka, Toshiei,Segawa, Hirozo,Takeuchi, Yasutomo,Takematsu, Tetsuo
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p. 1555 - 1560
(2007/10/02)
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