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Currently, there is no approved drug to combat dengue. Various quinoline derivatives are known for potential antimalarial, antiviral activities, etc. In the present work docking between 4-Amino-7-Chloroquinoline analogs was performed with dengue virus NS2B/NS3 protease using CB dock, a web server. Lys74, Ile165, Val147, Asn152, Asn167, Trp83 and Leu149 amino acid residues were found to be in contact with designed 4-Amino-7-Chloroquinoline analogs. Different modes of binding like hydrogen bonding, hydrophobic interactions, etc with designed compounds improve potential anti-dengue characteristics in silico. ADME results are in acceptable range.
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Currently, there is no approved drug to combat dengue. Various quinoline derivatives are known for potential antimalarial, antiviral activities, etc. In the present work docking between 4-Amino-7-Chloroquinoline analogs was performed with dengue virus NS2B/NS3 protease using CB dock, a web server. Lys74, Ile165, Val147, Asn152, Asn167, Trp83 and Leu149 amino acid residues were found to be in contact with designed 4-Amino-7-Chloroquinoline analogs. Different modes of binding like hydrogen bonding, hydrophobic interactions, etc with designed compounds improve potential anti-dengue characteristics in silico. ADME results are in acceptable range.
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A strategy combining collision cross section(CCS) prediction and quantitative structure-retention relationship(QSRR) model for quinoline and isoquinoline alkaloids was established based on UHPLC-IM-Q-TOF-MS and applied to Phellodendri Chinensis Cortex and Phellodendri Amurensis Cortex. The strategy included the following three steps.(1) The molecular features were extracted by the "find features" algorithm.(2) The potential quinoline and isoquinoline alkaloids were screened by filtering the original characteristic ions extracted from Phellodendri Chinensis Cortex and Phellodendri Amurensis Cortex by the established CCS vs m/z prediction interval.(3) According to the retention time of candidate compounds predicted by QSRR model, the chemical constituents were identified in combination with the characteristic fragment ions and pyrolysis law of secondary mass spectrometry. With the strategy, a total of 80 compounds were predicted, and 15 were identified accurately. The strategy is effective for the identification of small analogs of traditional Chinese medicine.
Subject(s)
Chromatography, High Pressure Liquid , Algorithms , Alkaloids , Isoquinolines , QuinolinesABSTRACT
Objective:To develop a tetramer probe targeting fibroblast activation protein (FAP), named 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)-4P(FAP inhibitor (FAPI)) 4, evaluate its biodistribution and PET image in FAP-positive-tumor bearing nude mice, and explore its feasibility as a novel radio-regent for treatment of FAP-positive tumor. Methods:FAP tetramer probe was constructed on the FAPI-46 motif with four mini-polyethylene glycol (PEG)(PEG 3) spacers between the four FAPI motifs, denoted as 4P(FAPI) 4. DOTA was used as the chelator for radiolabeling with 68Ga and 177Lu. The FAP binding characteristics were test by in vitro cell competitive binding experiment. Small-animal PET, in vivo biodistribution, and radionuclide targeting therapy were performed in HT-1080-FAP tumor bearing nude mice ( n=39). Independent-sample t test was performed to analyze tumor uptake data, and two-factor repeated measures analysis of variance was utilized to compare tumor volume data in radioactive isotope therapy. Results:Cell experiment showed that FAPI-tetramer and FAPI-monomer had similar half maximal inhibitory concentration values (3.29 and 2.15 nmol/L). 68Ga/ 177Lu radiolabeled FAPI-tetramer had better tumor uptake and retention than FAPI-monomer in small-animal PET and in vivo biodistribution experiment, with the tumor uptake for 177Lu-DOTA-4P(FAPI) 4 and 177Lu-FAPI-46 at 48 h of (18.72±1.32) vs (2.72±1.20) percentage activity of injection dose per gram of tissue (%ID/g) ( t=15.55, P<0.001). 177Lu-DOTA-4P(FAPI) 4 group showed best anti-tumor efficacy compared with 177Lu-FAPI-46 and control group in radionuclide targeting therapy. On the 2nd day after the start of treatment, the tumor volume in the tetramer treatment group was significantly smaller than that in the control group (mean difference 67.19 mm 3, P=0.049); on the 14th day after the start of treatment, the tumor volume in the tetramer treatment group was significantly smaller than that in the monomer treatment group (mean difference 414.33 mm 3, P=0.005). Conclusion:FAPI-tetramer can improve tumor uptake and retention ability compared with FAPI-46, and 177Lu-DOTA-4P(FAPI) 4 can be a promising radio-agent for FAP-positive tumor therapy.
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Objective: To evaluate new compounds synthesized by integrating quinoline, quinazoline, and acridine rings with the active moiety of (5-nitroheteroaryl) methylene hydrazine. Methods: A new series of compounds (1a, 1b, 2a, 2b, 3a, and 3b) were synthesized and evaluated for cytotoxicity against COS-7 cells using the MTT assay. In vitro anti-plasmodial activity of the compounds was measured against CQ-sensitive (3D7) and CQ-resistant (K1) Plasmodium (P.) falciparum strains. β-hematin assay was performed to assess the inhibitory effects of β-hematin formation for new compounds. Results: The synthetic compounds had anti-plasmodial activity against blood-stage of 3D7 [IC
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Three compounds, including scolosprine C(1), uracil(2) and hypoxanthine(3), were isolated and purified from the ethyl acetate fraction of centipede by silica gel normal-phase column chromatography, reversed-phase medium pressure preparation chromatography, and high-pressure semi-preparative HPLC. The structure was elucidated through a combination of spectroscopic analyses [such as nuclear magnetic resonance(NMR) and mass spectrometry(MS)] and literature review. Among them, compound 1 was a new quinoline alkaloid. In previous reports, we have described the isolation and structure elucidation of one new and two known quinoline alkaloids. In this paper, we would report the isolation and structure elucidation of scolosprine C in detail.
Subject(s)
Animals , Alkaloids , Arthropods , Chilopoda , QuinolinesABSTRACT
Abstract INTRODUCTION: The drugs currently available for leishmaniasis treatment have major limitations. METHODS: In vitro and in vivo studies were performed to evaluate the effect of a quinoline derivative, Hydraqui (7-chloro-4-(3-hydroxy-benzilidenehydrazo)quinoline, against Leishmania amazonensis. In silico analyses of absorption, distribution, metabolism, excretion, and toxicity (ADMET) parameters were performed. RESULTS: Hydraqui showed significant in vitro anti-amastigote activity. Also, Hydraqui-treated mice exhibited high efficacy in lesion size (48.3%) and parasitic load (93.8%) reduction, did not cause hepatic and renal toxicity, and showed appropriate ADMET properties. CONCLUSIONS: Hydraqui presents a set of satisfactory criteria for its application as an antileishmanial agent.
Subject(s)
Animals , Female , Quinolines/therapeutic use , Leishmania mexicana/drug effects , Leishmaniasis, Cutaneous/drug therapy , Antiprotozoal Agents/therapeutic use , Quinolines/chemistry , Leishmaniasis, Cutaneous/parasitology , Disease Models, Animal , Parasite Load , Mice , Mice, Inbred BALB CABSTRACT
Objective To investigate the chemical constituents of the fruits of Ficus carica. Methods The chemical constituents were isolated and purified with silica gel chromatography, Sephdex LH-20 and HPLC, and their structures were elucidated by spectral analysis including MS, NMR, IR spectroscopic analysis, elment analyzer, and chemical evidence. Results One new quinoline and two new anhydride compounds were isolated from ethyl acetate extract of the fruits of F. carica. The structures of the three new compounds were respectively defined as 4-hydroxyl-6-formyl-8α-methoxyl-quinoline-2-one (1), 5’β,6’α-[(di-ethyl)-5β,6β-cyclohexyl]- epoxyhexyl, cyclo-pentanhydride-[2,2,1]-2α,3β-cycloheptane (2), and 5’β,6’β-[di-(11-methylbutyl,11’-methylbutyl)-9,9’]-cyclo-8’- hexadiene-5α,6α-epoxyhexyl, cyclo-pentanhydride-[2,2,2,1]-2β,3α-cycloheptane (3). Conclusion These compounds were named figine K-1, figine G-1, and figine G-2, respectively.
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Objective: In order to clarify the characteristic chemical constituents and furnish applicable information to the basic research and quality control research related to the chemistry of traditional Chinese medicines for Corydalis Rhizoma,this paper investigated the chemical constituents of Corydalis Rhizoma extensively. Method: The dried-up and pulverized plant materials were extracted using 95% EtOH as solvent,the EtOH extract was fractionated using different solvents to afford the EtOAc-soluble and n-BuOH-soluble portion,respectively,among others. These two portions were subjected to procedures of isolation and purification on silica gel or ODS column chromatographies to afford monomers. 1D and 2D NMR and MS methods,along with comparison with the data of literatures,were used to identify the structures. Result: Twelve compounds,all belonging to alkaloids,were isolated and identified as d-corydaline(1),tetrahydrocoptisine(2),tetrahydropalmatine(3),tetrahydrocolumbamine(4),corybulbine(5),tetrahydrojatrorrhizine(6),dehydrocorydaline(7),dehydroglaucine(8),8-oxodihydrocoptisine(9),protopine(10),taxilamine(11),and pontevedrine(12). Of these compounds,the structure of 12 was a revised structure which was assigned by combined examinations of their 1D and 2D NMR spectra and MS data. Conclusion: Compounds 6 and 11 were reported from Corydalis Rhizoma for the first time. The structure of pontevedrine was verified as 1,2,9,10-tetramethoxy-6-methyl-4H-dibenzo[de,g]quinoline-4,5(6H)-dione.
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Objective: To study the quinoline alkaloids from the ethanol extract of Scolopendra subspinipes mutilans (SSM). Methods: The chemical constituents were isolated and purified by macroporous resin column, medium pressure preparation chromatography, and semi-preparative HPLC. Their structures were elucidated by IR, MS, and NMR experiments. Results: Three quinolone alkaloids were obtained and identified as 3-hydroxy-4-methoxyquinolin-8-yl hydrogen sulfate (1), jineol-8-sulfate (2), and jineol (3), respectively. Conclusion: Compound 1 is a new compound from SSM.
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The root bark of Dictamnus dasycarpus is one of common traditional Chinese medicines (TCMs). Quinoline alkaloids are one of the main active substances in this TCM and possess many biological activities including anti-titumor, anti-inflammation, anti-bacteria, anti-oxidation, and anti-platelet aggregation activities. In this study, eight quinoline alkaloids 1-8 were firstly separated from the root barks of D. dasycarpus. It was difficult to isolate more quinoline alkaloids from the remaining fraction 8 in D. dasycarpus by this conventional chemical separation, so the target analysis method combined LC-MS guided-separation of quinoline alkaloids from fraction 8 was established. MS/MS fragmentation patterns of eight quinoline alkaloids reference standard compounds 1-8 were studied by ultra-performance liquid chromatography-electrospary ionization-mass spectrometry (UPLC-ESI-MS/MS). Based on the feature fragment ion 200, the parent ion scan mode was established for the target analysis of quinoline alkaloids in fraction 8. Finally, 8-methoxyflindersine (9) and N-metilatanina (10) were discovered and isolated quickly from fraction 8 guided by LC-MS, and their structures were identified by NMR and MS. Among them, compound 10 was isolated from the genus Dictamnus for the first time. These results indicated that this method is not only quick and sensitive for analyzing the quinoline alkaloids, but also to effectively guided-separate this kind of alkaloids in the root barks of D. dasycarpus.
Subject(s)
Alkaloids , Chromatography, High Pressure Liquid , Dictamnus , Chemistry , Ions , Phytochemicals , Plant Roots , Chemistry , Quinolines , Spectrometry, Mass, Electrospray Ionization , Tandem Mass SpectrometryABSTRACT
Abstract Choisya ternata Kunth, C. ternata var. sundance Kunth and the hybrid Choisya 'Aztec-Pearl' are three related species belonging to the Rutaceae family. Ethanol extracts were prepared from the leaves of these three species and evaluated in relation to their antioxidant activity using in vitro and ex vivo models. The ethanol extracts belonging to the three species produced a very high antioxidant profile as evidenced by the DPPH radical scavenging activity, the determination of total phenolics and flavonoid equivalent. The generation of reactive species of oxygen in leukocytes stimulated with LPS was dramatically reduced when the three ethanol extracts were used. The alkaloids anhydroevoxine and choisyine were isolated from the ethanol extract of C. ternata using HEMWat (4:6:5:5) as the solvent system by means of high-speed countercurrent chromatography. This was the first time quinoline alkaloids were isolated from this species using HSCCC. These compounds were also assayed for their capacity to inhibit the generation of ROS in leukocytes stimulated by LPS and the results also suggested that they are reactive oxygenase inhibitors.
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ABSTRACT The present study investigated the antioxidant effect of a new class of quinoline derivatives (a-d) on assays in vitro. Lipid peroxidation, thiol peroxidase-like and free radical scavenging activities were determined to evaluate antioxidant activity of compounds. Thiol oxidase-like and δ-aminolevulinate dehydratase activities were performed as a toxicological parameter. A second objective of this study was to evaluate the in vivo antinociceptive effect of the compound with better antioxidant effect and without toxic effects in a model of nociception induced by formalin in mice. In liver, at 100 µM, compound a reduced the lipid peroxidation to the control levels, while compounds c and d partially reduced it. In brain, only compound d partially reduced the lipid peroxidation at 50 and 100 µM. Compound b did not have an effect on the lipid peroxidation. Thiol peroxidase-like and free radical scavenging activities are not involved in the antioxidant mechanisms of these compounds. Compounds did not present thiol oxidase-like activity and effect on the δ-aminolevulinate dehydratase. In vivo experiments showed that compound a caused an inhibition of licking time in the first and second phases, and edema formation induced by formalin. In conclusion, quinoline derivative without selenium presented better in vitro antioxidant effect and in vivo antinociceptive activity.
Subject(s)
Animals , Male , Rats , Quinolines/pharmacology , Selenium/pharmacology , Oxidative Stress/drug effects , Analgesics/pharmacology , Antioxidants/pharmacology , Oxidation-Reduction , Quinolines/chemistry , Pain Measurement , Free Radical Scavengers , Disease Models, Animal , Oxidoreductases Acting on Sulfur Group Donors/pharmacology , Porphobilinogen Synthase/pharmacologyABSTRACT
Objective: To study the alkaloids from Ervatamia hainanensis. Methods: The alkaloids were isolated and purified by silica gel, MCI, Sephadex LH-20 column chromatography, and semi-preparative HPLC, and their structures were elucidated by physical and spectroscopic analysis. Results: Twelve alkaloids were obtained and identified as coronaridine (1), 19-epi-heyneanine (2), 9,10-dimethoxycoronaridine (3), vobasine (4), vobasine N(4)-oxide (5), 3-oxo-19-epi-heyneanine (6), strictamine (7), deacetylakuammiline (8), pandine (9), rhazicine (10), rhazicine N(4)-oxide (11), and rhazimine (12). Conclusion: Compounds 8 and 10-12 are isolated from the genus Ervatamia Stapf for the first time, while compounds 3 and 5-7 are firstly obtained from E. hainanensis.
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Objective Based on the structure-activity relationships on the reported antifungal agents bearing quinoline or thiophene moieties ,novel compounds bearing both quinoline and thiophene were designed ,synthesized ,and evaluated for in vitro antifungal activity against Candida albicans .Methods With 5-cyanothiophene-2-carbaldehyde or 5-cyanothiophene-3-car-baldehyde as starting materials ,13 compounds were synthesized via reductive amination ,reduction of cyano group and amida-tion of quinoline-or isoquinoline-carboxylic acid .Their chemical structures were characterized by 1 H NMR and MS . In vitro antifungal screening against Candida albicans SC5314 was performed with the microbroth dilution method .Results All the compounds exhibited potent antifungal activities against Candida albicans .Among them ,compound 6k showed the highest an-tifungal activity with MIC80 value of 0 .5 μg/ml ,which is same potent as fluconazole .Conclusion The designed compounds bearing both quinoline and thiophene exhibited potent antifungal activities ,and deserve further research .
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Fourteen new compounds with 2,3-dihydro-1H-pyrrolo[3,2-c]-quinoline or 2,3,5,9b-tetrahydro- 1H-pyrrolo[3,2-c]quinoline scaffold were designed and synthesized, and their inhibitory activities against Kv2.1 were evaluated. As a result, 2,3-dihydro-1H-pyrrolo[3,2-c]quinoline derivatives 3a and 5a were identified as potent inhibitors of Kv2.1 with IC50 values of 10.2 and 9.0 μmol·L-1, respectively.
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Objective: To investigate the effect of Lianhua Shenjia Formula (this formula is extracted from the effective components of four traditional Chinese medicines: phillygenin, trichosanthin, codonopsis pilosulaglycoprotein and triterpenes compound of Cortex Periplocae) on β-catenin protein expression during the process of esophageal precancerous changes in C57BL/6 mice induced by 4-nitro quinoline1-oxide (4NQO), and to explore the possible mechanism of this formula inhibiting precancerous changes in esophagus. Methods: The expressions of β-catenin protein in different-stage esophageal precancerous lesion tissues in mice induced by 4NQO and before and after Lianhua Shenjia Formula treatment were detected by immunohistochemistry. Results: The abnormal expression rate of β-catenin protein in esophageal squamous cells was increased over time in 4NQO control group, and this rate reached 62.5% (10/16) in the 24th week, which was significantly higher than that in the normal control group (P < 0.01). The abnormal expression rates of β-catenin protein in Lianhua Shenjia Formula treatment group and all-trans retinoic acid (ATRA) treatment group were both decreased as compared with that of 4NQO control group (P < 0.01); however, there was no significant difference between Lianhua Shenjia Formula treatment group and ATRA treatment group. Conclusion: The Lianhua Shenjia Formula can inhibit the accumulation of β-catenin protein, and this may be one of the mechanisms of Lianhua Shenjia Formula inhibiting the development and progression of esophageal carcinoma.
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The present work describes the preparation of novel compounds based on the structure of 2- substituted benzo[b]-furo[2,3-h][1,6]napthyridin-5[4H]-one (10). Their methyl and methoxy derivatives were synthesized and their cytotoxicity evaluated against a cancer cell line HeLa. The analogue bearing methyl group on the system is three times more potent than the methoxy group. One could suggest that the methyl group activates the inhibitor’s site. These results provide new information on the structure activity relationship of these naphthyridine based systems.
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AIM@#To investigate the quinoline alkaloids from the roots of Dictamnus angustifolius G.Don ex Sweet (Rutaceae).@*METHOD@#The quinoline alkaloids were isolated by various column chromatographic methods and their structures were elucidated on the basis of spectral analysis.@*RESULTS@#A new quinoline alkaloid, 5-methoxylrobustine (1), along with five known quinoline alkaloids were obtained, and their structures were identified as dictamnine (2), robustine (3), isopteleine (4), γ-fagarine (5), and skimmianine (6). Cytotoxicity testing of these alkaloids showed that all of them had weak cytotoxic activities against human breast cancer cells (MCF7).@*CONCLUSION@#Compound 1 is a new quinoline alkaloid. Alkaloid 3 showed stronger anti-proliferation effect than the other alkaloids.
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Humans , Antineoplastic Agents, Phytogenic , Pharmacology , Therapeutic Uses , Breast Neoplasms , Drug Therapy , Cell Line, Tumor , Dictamnus , Chemistry , Hydroxyquinolines , Chemistry , Pharmacology , Therapeutic Uses , Molecular Structure , Phytotherapy , Plant Extracts , Chemistry , Pharmacology , Therapeutic Uses , Plant Roots , Chemistry , Quinolines , Chemistry , Pharmacology , Therapeutic UsesABSTRACT
PURPOSE: Acute side effects of radiation such as oral mucositis are observed in most patients. Although several potential radioprotective agents have been proposed, no effective agent has yet been identified. In this study, we investigated the effectiveness of synthetic compound 3-amino-3-(4-fluoro-phenyl)-1H-quinoline-2,4-dione (KR22332) as a radioprotective agent. MATERIALS AND METHODS: Cell viability, apoptosis, the generation of reactive oxygen species (ROS), mitochondrial membrane potential changes, and changes in apoptosis-related signaling were examined in human keratinocyte (HaCaT). RESULTS: KR22332 inhibited irradiation-induced apoptosis and intracellular ROS generation, and it markedly attenuated the changes in mitochondrial membrane potential in primary human keratinocytes. Moreover, KR22332 significantly reduced the protein expression levels of ataxia telangiectasia mutated protein, p53, and tumor necrosis factor (TNF)-alpha compared to significant increases observed after radiation treatment. CONCLUSION: KR22332 significantly inhibited radiation-induced apoptosis in human keratinocytes in vitro, indicating that it might be a safe and effective treatment for the prevention of radiation-induced mucositis.