共查询到20条相似文献,搜索用时 15 毫秒
1.
2.
Domínguez JN León C Rodrigues J Gamboa de Domínguez N Gut J Rosenthal PJ 《Journal of medicinal chemistry》2005,48(10):3654-3658
Phenylurenyl chalcone derivatives have been synthesized and tested as inhibitors of in vitro development of a chloroquine-resistant strain of Plasmodium falciparum, activity of the cysteine protease falcipain-2, in vitro globin hydrolysis, beta-hematin formation, and murine Plasmodium berghei malaria. The most active antimalarial compound was 1-[3'-N-(N'-phenylurenyl)phenyl]-3(3,4,5-trimethoxyphenyl)-2-propen-1-one 49, with an IC(50) of 1.76 microM for inhibition of P. falciparum development. Results suggest that chalcones exert their antimalarial activity via multiple mechanisms. 相似文献
3.
Yadav N Dixit SK Bhattacharya A Mishra LC Sharma M Awasthi SK Bhasin VK 《Chemical biology & drug design》2012,80(2):340-347
Twenty‐seven novel chalcone derivatives were synthesized using Claisen‐Schmidt condensation and their antimalarial activity against asexual blood stages of Plasmodium falciparum was determined. Antiplasmodial IC50 (half‐maximal inhibitory concentration) activity of a compound against malaria parasites in vitro provides a good first screen for identifying the antimalarial potential of the compound. The most active compound was 1‐(4‐benzimidazol‐1‐yl‐phenyl)‐3‐(2, 4‐dimethoxy‐phenyl)‐propen‐1‐one with IC50 of 1.1 μg/mL, while that of the natural phytochemical, licochalcone A is 1.43 μg/mL. The presence of methoxy groups at position 2 and 4 in chalcone derivatives appeared to be favorable for antimalarial activity as compared to other methoxy‐substituted chalcones. Furthermore, 3, 4, 5‐trimethoxy groups on chalcone derivative probably cause steric hindrance in binding to the active site of cysteine protease enzyme, explaining the relative lower inhibitory activity. 相似文献
4.
Synthesis and pharmacological evaluation of antioxidant chalcone derivatives of 2(3H)-benzoxazolones
Hocine Aichaoui Faouzi Guenadil Coco N. Kapanda Didier M. Lambert Christopher R. McCurdy Jacques H. Poupaert 《Medicinal chemistry research》2009,18(6):467-476
Chalcones featuring an analgesic/anti-inflammatory pharmacophore, i.e., the 2(3H)-benzoxazolone heterocycle, on the one hand, and a radical scavenger moiety, i.e., 2,6-di-t-butylphenol, on the other hand were synthesized by condensation of a ketone 2(3H)-benzoxazolone precursor with 3,5-di-t-butyl-4-hydroxybenzaldehyde. Among the various methods explored (acid homogenous or heterogenous catalysis, base catalysis),
heterogenous catalysis conditions using KSF Montmorillonite were found to be the most convenient. The E-geometry of the so-obtained chalcones was ascertained both by 1H and 13C-nuclear magnetic resonance (NMR) spectroscopy as well as B3LYP/6-31G** quantum mechanics calculations. Chalcones 1–8 were pharmacologically evaluated in vitro for their ability to prevent human low-density lipoprotein (LDL) copper-induced
oxidation using Cu2+ as oxidizing agent. Compound 4 emerged as the most promising agent as it was able to inhibit copper-mediated human LDL oxidation with an activity ten times
greater than that of Probucol, a reference antioxidant drug. 相似文献
5.
Satish K. Awasthi Nidhi Mishra Brajesh Kumar Manish Sharma Amit Bhattacharya Lokesh C. Mishra Virendra K. Bhasin 《Medicinal chemistry research》2009,18(6):407-420
Abstract Several new chalcone analogues were synthesized and evaluated as inhibitors of malaria parasite. Inhibitory activity was
determined in vitro against a chloroquine-sensitive Plasmodium falciparum strain of parasites. The compound 3-(4-methoxyphenyl)-1-(4-pyrrol-1-yl-phenyl)prop-2-en-1-one was found to be the most active
with 50% inhibition concentration (IC50) of 1.61 μg/ml. This inhibitory concentration is comparable to a prototype phytochemical chalcone, licochalcone A, with an
IC50 of 1.43 μg/ml. The present study suggests that small, lipophilic nitrogen heterocyclic ring A together with small hydrophobic
functionality at ring B can enhance antimalarial activity. These results suggest that chalcones are a class of compounds that
provides an option of developing inexpensive, synthetic therapeutic antimalarial agents in the future.
Graphical Abstract Claisen-Schmidt condensation method was employed to synthesize various substituted chalcones. Among all, 3-(4-Methoxyphenyl)-1-(4-pyrrol-1-yl-phenyl)prop-2-en-1-one
was found to be most effective with IC50 value of 1.6 μg/ml in vitro against chloroquine sensitive strain (3D7) of Plasmodium falciparum.
相似文献
6.
7.
8.
《Pharmacological reports : PR》2019,71(5):762-767
BackgroundPlasmodium falciparum dihydrofolate reductase (Pf-DHFR) is an essential enzyme in the folate pathway and is an important target for antimalarial drug discovery. In this study a modern approach has been undertaken to identify new hits of thiazole-1,3,5-triazine derivatives as antimalarials targeting Pf-DHFR.MethodsThe library of 378 thiazole-1,3,5-triazines were designed and subjected to ADME analysis. The compounds having optimal ADME score, was then evaluated by docking against wild and mutant Pf-DHFR complex. The resultant compound after screening from above these two methods were synthesized, and assayed for in vitro antimalarial against chloroquine-sensitive (3D-7) and chloroquine resistant (Dd-2) strains of P. falciparum.ResultsTwenty compounds were identified from the dataset based on considerable AlogP98 vs. PSA_2D confidence ellipse, ADME filter and TOPKAT toxicity analysis. Majority of compounds showed interaction with Asp54, Arg59, Arg122 and Ile 164 in docking analysis. Entire set of tested derivatives exhibited considerable activity at the tested dose against sensitive strain with IC50 values varying from 10.03 to 54.58 μg/ml. Furthermore, against chloroquine resistant strain, eight compounds showed IC50 from 11.29 to 40.92 μg/ml. Compound A5 and H16 were found to be the most potent against both the strains of P. Falciparum.ConclusionResults of the study suggested the possible utility of thiazole-1,3,5-triazines as new lead for identifying new class of Pf-DHFR inhibitor. 相似文献
9.
The development of new antimalarial drugs is an urgent priority considering the increasing prevalence of drug-resistant Plasmodium falciparum parasites. A series of pyrazoles are described as part of efforts directed toward the synthesis of some potent antimalarial agents. The replacement of the ester group as a substituent in the pyrazole ring by nitrile group caused a precipitous loss of activity as antimalarial due to the lack of hydrogen-bond formation. Further modification of the heterocyclic ring to give substituted aryl derivatives afforded potent antimalarial derivatives: methyl 5-amino-3-anisidinepyrazole-4-carboxylic acid 3a (IC50: 0.149 mumol/l) and methyl 5-amino-3-(m anisidin)pyrazole-4-carboxylic acid 3c (IC50: 0.15 mumol/l). The synthesis, structure-activity relationships (SAR), X-ray crystallography and pharmacological activity associated with these series of compounds are discussed. 相似文献
10.
Guianvarc'h D Duca M Boukarim C Kraus-Berthier L Léonce S Pierré A Pfeiffer B Renard P Arimondo PB Monneret C Dauzonne D 《Journal of medicinal chemistry》2004,47(9):2365-2374
A series of novel 4beta-substituted sulfonamide derivatives of 4'-O-demethyl-4-desoxypodophyllotoxin has been synthesized. Their effects on human DNA topoisomerase II and, in some cases, on tubulin polymerization were evaluated. Compounds 8a, 8c, 8f, 8g, 8n, 8q, 8r, and 8s and the synthetic precursor 4 are potent topoisomerase II poisons that induce double-stranded breaks in DNA, with either improved or similar activity compared to etoposide. Only the amino precursor, compound 5, was slightly active in tubulin polymerization inhibition assays. We observed that the derivatives bearing an aromatic ring on the 4beta-sulfonamide substituent were either less cytotoxic or equivalent to the parent drug, while the sulfonamides containing an aliphatic side chain and the amino-sulfonamide derivatives, except 8d and 8g, exhibited increased cytoxicity compared to etoposide. In vivo, against the P388 leukemia and the A-549 orthotopic model of lung carcinoma, the most promising compounds were the morpholino- and the piperazino-containing sulfonamides derivatives 8r and 8s. 相似文献
11.
《Pharmaceutical biology》2013,51(3):283-289
Context: Novel antimalarial agents are in demand due to the emergence of multidrug resistant strains. Ginseng, a medicinal plant with antiparasitic activity, contains components that can be used to treat the tropical disease malaria.Objective: Ginsenosides and polysaccharides are active components of ginseng. This study aimed to elucidate the ability of these compounds to inhibit the replication of Plasmodium yoelii in an attempt to determine whether the medicinal uses of ginseng are supported by pharmacological effects. New antimalarial compounds may be developed from ginsenosides and water-soluble ginseng polysaccharides (WGP).Materials and methods: Ginsenosides and ginseng polysaccharides were prepared from ginseng. Antimalarial activities were examined by 4-day tests and repository tests. Macrophage phagocytosis was tested in normal and malaria-bearing mice.Results: Ginseng polysaccharides could inhibit residual malaria infection. After a 6-day treatment, the parasitemia reductions of WGP and acidic ginseng polysaccharide (WGPA) were 55.66% and 64.73% at 200?mg/kg/day, respectively. Ginsenosides showed significant antimalarial activity on early infection. Protopanaxadiol-type ginsenosides caused 70.97% chemosuppression at 50?mg/kg/day, higher than 52.8% of total ginsenosides at the same dose.Discussion and conclusion: Protopanaxadiol-type ginsenosides have remarkably suppressive activity during early infection, while acidic ginseng polysaccharides have significant prophylactic activity against malaria by stimulating the immune system. We propose that the activity of ginsenosides is dependent upon non-specific carbohydrate interactions and that the activity of ginseng polysaccharides is due to immunological modulation. Ginsenosides and ginseng polysaccharides might have a potential application in antimalarial treatments. 相似文献
12.
R. Chauhan J. Dwivedi A. A. Siddiqi Anees D. Kishore 《Pharmaceutical Chemistry Journal》2011,44(10):542-550
A series of previously unreported (2Z)-2-(1H-indol-1-yl)-3-(4-substituted phenyl)-1-phenylprop-2-en-1-one (5a–d) have been synthesized from easily accessible 2-(1H-indol-1-yl)-1-phenylethanone (3), which was obtained via a reaction of indole (1) with chloromethylphenyl ketone (2). The structures of the synthesized products have been elucidated using IR, 1H NMR, and mass-spectroscopic data and elemental analyses. The final products were screened for their antimicrobial activity.
Excellent results were obtained against both bacteria and fungi. In conclusion, we have developed a novel, convenient and
simple method for the preparation of indole – chalcone hybrid compounds via the reaction of indole derivative with carbonyl
compounds in the presence of a strong base. The rapid conversion, excellent yield, utilization of a base, and operational
simplicity are great advantages of the proposed method. 相似文献
13.
Synthesis and evaluation of antiinflammatory activity of substituted chalcone derivatives 总被引:1,自引:0,他引:1
Xue-Wu Zhang Dong-Hai Zhao Ying-Chun Quan Liang-Peng Sun Xiu-Mei Yin Li-Ping Guan 《Medicinal chemistry research》2010,19(4):403-412
In an effort to develop potent antiinflammatory agents, a series of substituted chalcone derivatives was synthesized and evaluated for antiinflammatory activity through monitoring of their ability to inhibit xylene-induced ear edema in mice. Some of the tested compounds exhibited significant activity, and compounds 3f [(E)-1-(2,4-dihydroxyphenyl)-3-(4-dimethylamino)phenyl)prop-2-en-1-one] and 3h [(E)-3-(4-chlorophenyl)-1-(2,4-dihydroxyphenyl)prop-2-en-1-one] showed the highest antiinflammatory activity (62 and 68% inhibition, respectively, 2 h before administration), comparable with or even slightly more potent than the reference drug ibuprofen (53%). Furthermore, the structure–activity relationship of these substituted chalcone derivatives was demonstrated. 相似文献
14.
Hiba Iqbal Visakh Prabhakar Atul Sangith Baby Chandrika Ranganathan Balasubramanian 《Medicinal chemistry research》2014,23(10):4383-4394
A library of ring-A-monosubstituted chalcone derivatives (4a–4i, 5a and 5b) was designed and synthesised. The structures as well as the identities of these compounds were established on the basis of spectral (1H NMR, 13C NMR, FT-IR and Mass) and elemental (C, H, N) analyses. All the derivatives were evaluated for their anti-inflammatory and antioxidant activities in vitro using the inhibition of protein denaturation and 2,2-diphenyl-1-picrylhydrazyl radical scavenging assays, respectively. The results indicated a promising anti-inflammatory activity for most of the synthesised compounds with many derivatives showing activities similar to or greater than that of the standard. The sulphonamide-substituted chalcones 4h, 4i, 5a and 5b were found to be the most active derivatives across the concentration range tested. However, all the derivatives exhibited rather mild antioxidant activity compared to the ascorbic acid standard. Interestingly, it was observed that the unsubstituted parent chalcone was one of the optimal compounds with only the trifluoromethyl analogue 4a showing better activity as an antioxidant. The two regioisomeric aminochalcones and 4′-cyanochalcone 4b also seemed to possess decent antioxidant potential. 相似文献
15.
Guan LP Nan JX Jin XJ Jin QH Kwak KC Chai KY Quan ZS 《Archives of pharmacal research》2005,28(1):81-86
The hepatoprotective effects of chalcone derivatives were evaluated in D-galactosamine/lipopolysaccharide (D-GalN/LPS)-induced fulminant hepatic failure in mouse. Thirteen chalcone derivatives were synthesized for study and their hepatoprotective effects were evaluated by assessing aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in serum. Chalcone preparations were injected into mice at 12 h and 1 h before intraperitoneal injection of D-GalN/LPS. After abdominal administration, changes in AST and ALT between the control and treated groups were observed. Ten of the synthesized chalcone derivatives exhibited inhibitory effects on D-GalN/LPS-induced levels of AST and ALT in mice. Compounds 2, 3, 8, 9, and 12 markedly reduced serum AST and ALT at 8 h, inhibited hepatocyte necrosis and showed significant hepatoprotective activities. The activity of compound 3 was compared with the bifendate (DDB) through oral administration. Compound 3 showed much higher inhibitory effects than bifendate for decreasing AST and ALT activity. The results indicate that compound 3 has strong hepatoprotective activity through suppression of tumor necrosis factor-alpha (TNF-alpha) preduction, reduction of the histological change in the liver, and attenuated of hepatocyte apoptosis confirmed by DNA fragmentation assay. 相似文献
16.
Gul HI Yerdelen KO Gul M Das U Pandit B Li PK Secen H Sahin F 《Archiv der Pharmazie》2007,340(4):195-201
A new series of mono Mannich bases of 4'-hydroxychalcones 2a-e carrying a variety of aryl groups was synthesized and the in vitro cytotoxic activities of the new compounds were screened against PC-3 cell lines. Bioactivities of 2a-e, which are reported for the first time in this study, were compared against their precursor 4'-hydroxychalcones 1a-e. Compound 2b was found to be the most potent (IC(50 )= 3.7 microM) among the compounds synthesized. In addition, the compounds 1a-c and 2d showed moderate cytotoxicity. Incorporation of the 3'-piperidinomethyl group in 1b and 1d raised the potency by 1.68 and 2.19 times respectively and, therefore, seemed to be a noteworthy molecular modification. Correlations were noted between cytotoxicity and one or more physiochemical constants of the aryl ring as well as log P values for the compounds 2a-e. The significant improvement of cytotoxicity of 2b, 2d, and 2e against PC-3 cell lines compared with their chalcone precursors suggests that the incorporation of a piperidinomethyl group is a useful molecular modification and further development of these compounds as candidate cytotoxic agents may be warranted. 相似文献
17.
Liu X Wang X Li Q Kozar MP Melendez V O'Neil MT Lin AJ 《Journal of medicinal chemistry》2011,54(13):4523-4535
A series of 2-guanidino-4-oxoimidazoline (deoxo-IZ) derivatives was prepared and showed potent antimalarial activities in rodent and Rhesus models. Compound 8e, the most potent analogues of this series, is the first non-8-aminoqinoline antimalarial that demonstrated radical curative activity in non-human primate by oral route and showed causal prophylactic activity comparable to that of the commonly used clinical drugs in Rhesus monkeys infected with sporozoites of Plasmodium cynomolgi. The metabolic stability and metabolites profile indicated that the new deoxo-IZ derivatives (8) may act as prodrugs of the corresponding IZ (1 and 2) derivatives. 相似文献
18.
Synthesis of fluorine-containing sulfonamide derivatives 总被引:1,自引:0,他引:1
N Saito T Kurihara S Yasuda K Yamanaka S Tsuruta 《Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan》1968,88(12):1610-1615
19.
新型查耳酮衍生物的合成及其初步抗蛋白酪氨酸 激酶(PTKs)活性研究 总被引:1,自引:0,他引:1
目的 设计合成一系列全新的查耳酮类衍生物,并初步测试其蛋白酪氨酸激酶(PTKs)抑制活性。方法 以间二甲苯为原料,经硝化、还原、水解、甲氧甲基保护等反应得到中间体取代苯乙酮,该中间体再与取代苯甲醛发生羟醛缩合反应后脱保护基得到目标化合物。采用酶联免疫吸附法(ELISA),以金雀异黄素为阳性对照,对目标化合物进行体外 PTKs 抑制活性检测。 结果与结论 合成了 10 个查耳酮衍生物,其中 9 个是未见报道的新化合物,10 个化合物的结构经核磁共振氢谱和质谱确证。化合物 6a 及新化合物 6b、6c 和 6d 对 PTKs 具有良好的抑制活性。 相似文献
20.
Synthesis and antimalarial activity of artemisinin derivatives containing an amino group 总被引:1,自引:0,他引:1
Li Y Zhu YM Jiang HJ Pan JP Wu GS Wu JM Shi YL Yang JD Wu BA 《Journal of medicinal chemistry》2000,43(8):1635-1640
In search of water-soluble artemisinin derivatives that are more stable than sodium artesunate, over 30 derivatives containing an amino group (compounds 3-5) were synthesized and tested in mice. All products tested (except 5a and 5b) are the beta isomers. These basic compounds combined with organic acids (oxalic acid, maleic acid, etc. ) to yield the corresponding salts. Generally, the maleates have better solubility in water than the corresponding oxalates. The aqueous solutions of these salts can be kept at room temperature for several weeks without any discernible decomposition. Compounds 3f, 3h, and 3r are much more active against P. berghei than artesunic acid by oral administration and therefore were further tested in monkeys. However, their oral efficacies are poorer than that of artesunic acid against P. knowlesi in rhesus monkeys. It is interesting to note that 3f, 3h, and 3r showed much lower efficacies against P. berghei when they were administered subcutaneously than orally. 相似文献