607-67-0Relevant academic research and scientific papers
Synthesis, spectroscopic investigations and computational study of monomeric and dimeric structures of 2-methyl-4-quinolinol
Pourmousavi, Seied Ali,Kanaani, Ayoub,Ghorbani, Fatemeh,Damghani, Kobra Khorsi,Ajloo, Davood,Vakili, Mohamad
, p. 1237 - 1274 (2016)
The present study aimed to determine an efficient and solvent-free method to synthesize 2-methyl-4-quinolinol (2MQ, also known as 4-hydroxy-2-methylquinoline) and includes spectroscopic investigations and computational studies. Molecular geometry and vibrational wavenumbers of 2MQ were investigated using the density functional (DFT/B3LYP) method with 6-311++G(d,p) and 6-311++G(2d,p) basis sets. According to calculations, the keto form of 2MQ is more stable than the annual form, and the dimeric conformation is predicted to be more stable than the monomeric conformations. A detailed analysis of the nature of the hydrogen bonding, using topological parameters such as electronic charge density, Laplacian, kinetic and potential energy density evaluated at the bond critical point, is also presented. The 1H nuclear magnetic resonance chemical shifts of the molecule were calculated by the GIAO method. The molecule orbital contributions were studied by using total (TDOS) and partial (PDOS) density of states. The UV-visible spectrum of the compound was recorded and the electronic properties, such as HOMO and LUMO energies, were investigated by the time-dependent DFT (TD-DFT) approach. The linear polarizability (α) and the first-order hyperpolarizability (β) values of the investigated molecule were computed using DFT quantum mechanical calculations. The results show that the 2MQ molecule may have a nonlinear optical comportment with non-zero values. The stability and charge delocalization of the molecule was studied by natural bond orbital analysis. In addition, a molecular electrostatic potential map of the title compound was studied for predicting the reactive sites. Local reactivity descriptors, such as Fukui functions, local softness and electrophilicity indices analyses, were studied to determine the reactive sites within the molecule.
Hydrolyses of 2- and 4-Fluoro N-Heterocycles. 3. Nucleophilic Catalysis by Buffer Bases in the General Acid Catalyzed Hydrolysis of 4-Fluoroquinaldine
Muscio, Oliver J.,Theobald, Paula G.,Rutherford, Denise R.
, p. 166 - 171 (1989)
Pseudo-first-order rate constants and catalytic rate constants are reported for the buffer-catalyzed hydrolysis of 4-fluoroquinaldine (1) in carboxylic acid and phosphoric acid buffers.The buffer catalysis is consistent with specific acid, general base catalysis.Hydrolyses in 99percent 18O-labeled water with 0.04 M unlabeled acetate, and complementary hydrolyses in unlabeled water with 90percent 18O-labeled acetate, indicate that the predominant catalytic mode for the acetic acid/acetate buffer system is nucleophilic catalysis by the acetate anion coupled with specific acid catalysis.The other buffers presumably react in a similar manner.A Broensted-type plot of the catalytic rate constants for hydrolysis of protonated 1 has a slope of 0.57, with formate deviating positively from the line determined by acetate, chloroacetate, monohydrogen phosphate, and water.This Broensted slope is less than that found for hydrolysis of the 2-fluoro-1-methylpyridinium ion, 2, but is still within the range expected for aromatic nucleophilic substitution.Rate constants and 18O-labeling results for hydrolysis in acetate buffer are also reported for 4-acetoxyquinaldine (3), the proposed intermediate in the acetate-catalyzed hydrolysis of 1.
Hydrolyses of 2- and 4-Fluoro N-Heterocycles. 4. Proton Inventories of the Hydrolyses of 2-Fluoro-1-methylpyridinium Iodide, 4-Fluoroquinaldine, and 2-Chloro-1-methylpyrimidinium Triflate
Muscio, Oliver J.,Meng, Jialun,Wang, Haisheng,Shi, Songyuan
, p. 6454 - 6459 (1992)
Rate constants for the hydrolyses of 2-fluoro-1-methylpyridinium iodide (3), 4-fluoroquinaldine (4), and 2-chloro-1-methylpyrimidinium triflate (5) in 2 * 10-3 M aqueous sulfuric acid, in D2O/D2SO4, and in mixed H2O/H2SO4-D2O/D2SO4 media are reported.Significant solvent deuterium kinetic isotope effects are evident, with kH/kD = 2.07 for 3, 1.62 for 4, and 2.12 for 5.The results of the proton inventories for the hydrolyses of 3 and 5 are best fit by a form of the Gross-Butler equation for three nearly equivalent sites with fractionation factors of 0.78.The proton inventory of 4 does not yield a unique solution to the Gross-Butler equation, but the results are also consistent with three transition state sites with nearly equal fractionation factors of 0.72-0.78, as well as an additional transition-state site with Φ > 1 and a reactant site with Φ /= 1.These proton inventories are consistent with mechanisms in which nucleophilic addition of water in the rate-determining step is assisted by proton-transfer to a second water molecule, with development of an "immature hydronium ion" in the transition state.Mechanisms with cyclic proton transfer are also consistent, but are less satisfactory as hydrolysis routes.
Synthesis, Structure-Activity Relationship, and Antimalarial Efficacy of 6-Chloro-2-arylvinylquinolines
Huang, Guang,Murillo Solano, Claribel,Melendez, Joel,Shaw, Justin,Collins, Jennifer,Banks, Robert,Arshadi, Arash Keshavarzi,Boonhok, Rachasak,Min, Hui,Miao, Jun,Chakrabarti, Debopam,Yuan, Yu
, p. 11756 - 11785 (2020/11/26)
There is an urgent need to develop new efficacious antimalarials to address the emerging drug-resistant clinical cases. Our previous phenotypic screening identified styrylquinoline UCF501 as a promising antimalarial compound. To optimize UCF501, we herein report a detailed structure-activity relationship study of 2-arylvinylquinolines, leading to the discovery of potent, low nanomolar antiplasmodial compounds against a Plasmodium falciparum CQ-resistant Dd2 strain, with excellent selectivity profiles (resistance index 200). Several metabolically stable 2-arylvinylquinolines are identified as fast-acting agents that kill asexual blood-stage parasites at the trophozoite phase, and the most promising compound 24 also demonstrates transmission blocking potential. Additionally, the monophosphate salt of 24 exhibits excellent in vivo antimalarial efficacy in the murine model without noticeable toxicity. Thus, the 2-arylvinylquinolines represent a promising class of antimalarial drug leads.
Triphenylamine - quinoline derivatives and adopts its modification for detecting the oncogene related G - quadruplex optical fiber sensor
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Paragraph 0047-0051, (2019/07/10)
The invention belongs to the field of molecular biology, in particular to triphenylamine - quinoline derivatives and adopts its modification for detecting the oncogene related G - quadruplex optical fiber sensor, the present invention provides a new structure of the triphenylamine - quinoline derivatives, the quinoline derivative by the method of the present invention modified with activated hydroxyl of the surface layer of the optical fiber sensor of the optical fiber, the optical fiber sensor can be quickly specific detection HRAS G - quadruplex and HTG - 21 G - quadruplex, makes up for the optical fiber DNA sensor detecting G4 - DNA vacancies of the chain, since many of the cancer disease is due to the initiation of the cells in vivo G4 - DNA over-expression of the chain, the invention is specific detection G4 DNA offers a high-efficient and swift sensor, the sensor is expected to be applied to the biological and clinical analysis.
Design, synthesis, biological evaluation, and molecular modeling studies of quinoline-ferulic acid hybrids as cholinesterase inhibitors
Mo, Jun,Yang, Hongyu,Chen, Tingkai,Li, Qihang,Lin, Hongzhi,Feng, Feng,Liu, Wenyuan,Qu, Wei,Guo, Qinglong,Chi, Heng,Chen, Yao,Sun, Haopeng
, (2019/10/05)
A series of quinoline-ferulic acid hybrids has been designed, synthesized, and evaluated as cholinesterase inhibitors. Most of the compounds showed good inhibitory activities toward both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Among them, 10f was found to be the most potent inhibitor against AChE (IC50 = 0.62 ± 0.17 μM), and 14 was the most potent inhibitor against BChE (IC50 = 0.10 ± 0.01 μM). Representative compounds, such as 10f and 12g, act in a competitive manner when they inhibit AChE or BChE. Molecular docking and dynamic simulation revealed that the synthesized compounds bind to the target by simultaneously interacting with the catalytic active site (CAS) and the peripheral anionic site (PAS) of both AChE and BChE. The U-shaped confirmation was preferred when 12g bound to BChE, which was different from the linear conformation of 10f bound to AChE. Cell-based assays have confirmed the moderate neuroprotective effects of compounds 10f and 12g against H2O2-induced oxidative damage towards PC12 cells. Moreover, the hepatotoxicity of 12g was lower than that of tacrine, indicating its potential safety as an anti-Alzheimer's agent. In summary, we report a new chemotype of multifunctional hybrid, which may be further modified to develop new anti-Alzheimer's agents.
Syntheses and evaluation of new Quinoline derivatives for inhibition of hnRNP K in regulating oncogene c-myc transcription
Shu, Bing,Zeng, Ping,Kang, Shuangshuang,Li, Peng-Hui,Hu, Dexuan,Kuang, Guotao,Cao, Jiaojiao,Li, Xiaoya,Zhang, Meiling,An, Lin-Kun,Huang, Zhi-Shu,Li, Ding
, p. 1 - 17 (2019/01/04)
Aberrant overexpression of heterogeneous nuclear ribonucleoprotein K (hnRNP K) is a key feature in oncogenesis and progression of many human cancers. hnRNP K has been found to be a transcriptional activator to up-regulate c-myc gene transcription, a critical proto-oncogene for regulation of cell growth and differentiation. Therefore, down-regulation of c-myc transcription by inhibiting hnRNP K through disrupting its binding to c-myc gene promoter is a potential approach for cancer therapy. In the present study, we synthesized and screened a series of Quinoline derivatives and evaluated their binding affinity for hnRNP K. Among these derivatives, (E)-1-(4-methoxyphenyl)-3-(4-morpholino-6-nitroquinolin-2-yl)prop-2-en-1-one (compound 25) was determined to be the first-reported hnRNP K binding ligand with its KD values of 4.6 and 2.6 μM measured with SPR and MST, respectively. Subsequent evaluation showed that the binding of compound 25 to hnRNP K could disrupt its unfolding of c-myc promoter i-motif, resulting in down-regulation of c-myc transcription. Compound 25 showed a selective anti-proliferative effect on human cancer cell lines with IC50 values ranged from 1.36 to 3.59 μM. Compound 25 exhibited good tumor growth inhibition in a Hela xenograft tumor model, which might be related to its binding with hnRNP K. These findings illustrated that inhibition of DNA-binding protein hnRNP K by compound 25 could be a new and selective strategy of regulating oncogene transcription instead of targeting promoter DNA secondary structures such as G-quadruplexes or i-motifs.
Synthesis and identification of quinoline derivatives as topoisomerase I inhibitors with potent antipsoriasis activity in an animal model
Zhang, Wen-Jin,Li, Peng-Hui,Zhao, Min-Cong,Gu, Yao-Hao,Dong, Chang-Zhi,Chen, Hui-Xiong,Du, Zhi-Yun
, (2019/05/10)
Psoriasis is a chronic inflammatory and immune-mediated skin disease. Although certain agents have shown clinical success in treating psoriasis, development of safe and effective strategies for the treatment of this condition remains important. Research suggests that DNA topoisomerase I (Topo I)inhibitors may have potent psoriasis-ameliorating effects. Here, 25 quinoline derivatives were synthesized and identified as Topo I inhibitors. These compounds inhibited the 12–O–tetradecanoylphorbol-13-acetate-induced mouse ear inflammation. The most potent analogs, 5i and 5l, suppressed the expression of inflammatory cytokines in lipopolysaccharide-stimulated HaCaT cells. Additionally, the lead compounds significantly improved imiquimod-induced psoriasis-like inflammation in mice. Moreover, the expression levels of cytokines and inflammatory mediators, such as interleukin (IL)-17A, IL-22, IL-23, nuclear factor-κB subunit p65, tumor necrosis factor-α, and interferon-γ, were dramatically inhibited in the dorsal skin of 5i- and 5l-treated mice. These findings indicate that the inhibition of Topo I activity may potentially be an effective strategy for psoriasis treatment.
Design, synthesis and anti-HIV-1 activity of modified styrylquinolines
Mahajan, Shivani,Gupta, Shiv,Jariwala, Nisha,Bhadane, Deepali,Bhutani, Late K.K.,Kulkarni, Smita,Singh, Inder Pal
, p. 937 - 944 (2018/08/17)
Background: Drug resistance and reservoirs of latent viral infection have prevented total eradication of the HIV-virus which underlines the need for continuous efforts in the discovery of new anti-HIV agents. The present study deals with the synthesis of novel compounds based on naturally occurring scaffolds and their evaluation as potential anti-HIV agents. Objective: Design and synthesis of styrylquinoline scaffold based new molecules and evaluation of their anti-HIV-1 activity. Methods: A series of forty three new styrylquinolines (SQLs) was designed and synthesized. The newly synthesized compounds were tested for anti-HIV-1 activity against HIV-1VB59 and HIV-1UG070 primary isolates in TZM-bl cell lines. Results: The most active compounds 9 and 34 (IC50 = 0.5-4.0 μM), also exhibited significant inhibition activity against HIV-1VB51 primary isolate in PBMCs (IC50 = 7.3 μM). Compounds 9 and 34 were also found to inhibit HIV-1 entry into host cells and fusion inhibitory activities. The study encourages further exploration of SQL nucleus to design anti-HIV-1 agents. Conclusion: The study encourages further exploration of SQL nucleus to design anti-HIV-1 agents.
NEW TARGETED CYTOTOXIC ISOCOMBRETAQUINOLINE DERIVATIVES AND CONJUGATES THEREOF
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Paragraph 00112; 00113; 00138, (2018/10/25)
The present invention is directed to novel natural product-derived combretastatin- based compounds useful as payloads in drug-conjugates constructs with cell target binding moieties (CTBM) and payload-linker compounds useful in connection with drug conjugates. The present invention further relates to new isoNH2CombretaQuinoline compositions including the aforementioned payloads, payload-linkers and drug conjugates, and methods for using these payloads, payload-linkers and drug conjugates, to treat pathological conditions including cancer.
