共查询到20条相似文献,搜索用时 31 毫秒
1.
The parallel artificial membrane permeation assay (PAMPA) was developed as a model for the prediction of transcellular permeation in the process of drug absorption. Our research group has measured the PAMPA permeability of peptide‐related compounds, diverse drugs, and agrochemicals. This work led to a classical quantitative structure–activity relationship (QSAR) equation for PAMPA permeability coefficients of structurally diverse compounds based on simple physicochemical parameters such as lipophilicity at a particular pH (log Poct and |pKa?pH|), H‐bond acceptor ability (SAHA), and H‐bond donor ability (SAHD). Since the PAMPA permeability of lipophilic compounds decreased with their apparent lipophilicity due to the unstirred water layer (UWL) barrier on membrane surfaces and to membrane retention, a bilinear QSAR model was introduced to explain the permeability of a broader set of compounds using the same physicochemical parameters as those used for the linear model. We also compared PAMPA and Caco‐2 cell permeability coefficients of compounds transported by various absorption mechanisms. The compounds were classified according to their absorption pathway (passively transported compounds, actively transported compounds, and compounds excreted by efflux systems) in the plot of Caco‐2 vs. PAMPA permeability. Finally, based on the QSAR analyses of PAMPA permeability, an in silico prediction model of human oral absorption for possibly transported compounds was proposed, and the usefulness of the model was examined. 相似文献
2.
Bhanubhai N. Suhagia Mahesh T. Chhabria Ashlesha G. Makwana 《Journal of enzyme inhibition and medicinal chemistry》2013,28(6):681-691
A series of N1-(substituted)aryl-5,7-dimethyl-2-(substituted)pyrido(2,3-d)pyrimidin-4(3H)-one was designed on the basis of the triangular pharmacophoric requirement of histamine H1-receptor antagonists. The designed series was synthesized by cyclo-condensation of monoaryl thiourea with ethyl cyanoacetate in the presence of dry HCl gas to give N1-(substituted aryl)-2-mercaptopyrimidine-4(3H)-one, which on cyclo-condensation with acetylacetone gave the pyridopyrimidinone. Further methylation of the mercapto group at C-2 with methyl iodide followed by nucleophilic displacement of the methylmercapto group by various amines gave the targeted compounds. All the synthesized compounds were screened for histamine H1-receptor antagonistic activity by the in vitro method of inhibition of the isotonic contraction induced by histamine on isolated guinea pig ileum using cetirizine as a standard drug. All the compounds exhibited potent histamine H1-receptor antagonistic activity with pA2 values from 7.30– 9.75 (cetirizine, pA2 value 9.40). The potent compounds were screened for their in vivo antihistaminic activity by protection of animal from asphyxic shock. The sedative potential of potent compounds was checked on albino mice by photoactometer and they had comparative sedative potential to the standard drug cetirizine. None of the compound exhibited anticholinergic activity in the in vitro rat ileum model. 相似文献
3.
Koji Yamada Kentaro Shoji Mitsuo Mori Takashi Ueyama Noritaka Matsuo Shiro Oka Kazuo Nishiyama Michihiro Sugano 《In vitro cellular & developmental biology. Animal》1999,35(3):169-174
Summary The effect of phenolic compounds in foodstuffs on histamine and leukotriene B4 (LTB4) release from rat peritoneal exudate cells and their antioxidative activity were examined to assess their antiallergenic
activities. Among them, triphenols such as pyrogallol and gallic acid inhibited histamine release from the cells, but diphenols
did not. On the other hand, o- and p-diphenols such as catechol and hydroquinone with strong antioxidative activity inhibited LTB4 release as strongly as pyrogallol, but an m-derivative resorcinol with weak antioxidative activity did not. Though carboxylated compounds and their noncarboxylated counterparts
were antioxidative, the former exerted a much weaker inhibitory effect on the LTB4 release than the latter. In flavonols, only myricetin with a triphenolic B ring strongly inhibited histamine release, but
all flavonols strongly suppressed LTB4 release irrespective of the number of OH groups in the B ring. Among flavonoids with an o-diphenolic B ring, flavonol and flavone with a C4-carbonyl group strongly inhibited LTB4 release, whereas the activity of anthocyan without C4-carbonyl was much weaker than the above compounds. These results suggest that triphenolic structure is essential for the
inhibition of histamine release. On the other hand, antioxidative activity and membrane permeability of phenolic compounds
seemed to be essential for the inhibition of LTB4 release. In addition, the C4-carbonyl group seemed to be important for strongly inhibiting LTB4 release. 相似文献
4.
Xiao-San Li Xiao-Yan Liang Ming-Shang Liu Qi-Lin Wang He-Hui Zhan Zhi-Peng Xu Li Liu Yong-Mei Huang Mao-Xun Yang Hui Luo 《化学与生物多样性》2023,20(3):e202300082
Five new C21-steroidal sapogenins ( 1 – 5 ) named cynotogenins J−N, were isolated from the acid hydrolysate of Cynanchum otophyllum roots. Their structures were established by extensive spectroscopic analysis (UV, IR, HR-ESI-MS, and NMR). Most notably, compounds 1 – 3 harboring a rare 5β,6β-epoxy group in the C21-steroidal skeleton of Cynanchum plants. All compounds were evaluated for their cytotoxicities against multiple cancer cell lines, in which compounds 5 showed weak cytotoxicity against HepG2 cancer cells with IC50 values of 44.90 μM. 相似文献
5.
Ranju Bansal Gulshan Kumar Deepika Gandhi Louise C. Young Alan L. Harvey 《化学与生物多样性》2011,8(7):1290-1300
A new series of 1H‐imidazol‐1‐yl substituted 8‐phenylxanthine analogs has been synthesized to study the effects of the imidazole group on the binding affinity of compounds for adenosine receptors. Competition binding studies of these compounds were carried out in vitro with human cloned receptors using [3H]DPCPX and [3H]ZM 241385 as radioligands at A1 and A2A adenosine receptors, respectively. The effect of the substitution pattern of the (imidazolyl)alkoxy group on various positions of the phenyl ring at C(8) was also studied. The xanthine derivatives displayed varying degrees of affinity and selectivity towards A1 and A2A receptor subtypes despite a common but variedly substituted Ar C(8). 相似文献
6.
Twelve naturally-occurring organosulfur compounds were investigated as inhibitors of cytochrome P450 1 (CYP450 1)-mediated activation of benzo[a]pyrene (B[a]P) in human hepatoma (HepG2) cells. Inhibition depended on the presence of a diallyl group and the number of S atoms. Diallyl trisulfide (DATS), with a diallyl group and three S atoms, had the highest activity with an IC50 of 0.4 mM, and 1.5-fold higher potency than diallyl disulfide (DADS) containing a diallyl group and two S atoms. Organosulfur compounds containing an alkyl group were less effective, or even ineffective, inhibitors of both CYP450 1 and B[a]P-induced cytotoxicity than DADS and DATS. Alliin and S-allyl cysteine containing the S-cysteinyl group had no inhibition. 相似文献
7.
Xiaojun Xu Jingli Cheng Yong Zhou Chulong Zhang Xiaoming Ou Weike Su Jinhao Zhao Guonian Zhu 《化学与生物多样性》2013,10(4):600-611
Twenty new trichodermin derivatives, 2a – 5 , containing alkoxy, acyloxy, and Br groups in 4‐, 8‐, 9‐, 10‐ and 16‐positions were synthesized and characterized. The antifungal activities of the new compounds against rice false smut (Ustilaginoidea virens), rice sheath blight (Rhizoctonia solani), and rice blast (Magnaporthe grisea) were evaluated. The results of bioassays indicated that the antifungal activities were particularly susceptible to changes at 4‐, 8‐, and 16‐positions, but low to changes at 9‐ and 10‐positions. Most of these target compounds exhibited good antifungal activities at the concentration of 50 mg l?1. Compound 4 (9‐formyltrichodermin; EC50 0.80 mg l?1) with an CHO group at 9‐position displayed nearly the same level of antifungal activity against Ustilaginoidea virens as the commercial fungicide prochloraz (EC50 0.82 mg l?1), while compound 3f ((8R)‐8‐{[(E)‐3‐phenylprop‐2‐enoyl]oxy}trichodermin; EC50 3.58 and 0.74 mg l?1) with a cinnamyloxy group at C(8) exhibited much higher antifungal activities against Rhizoctonia solani and Magnaporthe grisea than the commercial fungicides prochloraz (EC50 0.96 mg l?1) and propiconazole (EC50 5.92 mg l?1), respectively. These data reveal that compounds 3f and 4 possess high antifungal activities and may serve as lead compounds for the development of fungicides in the future. 相似文献
8.
《Bioscience, biotechnology, and biochemistry》2013,77(6):1130-1132
The antifeedant activity toward larvae of Pieris rapae crucivora of aromatic carbonyl compounds was studied. When an H atom of aldehyde group of aromatic aldehydes was replaced by a CH3 group, it was observed that arylmethylketones were more active toward larvae than aromatic aldehydes. 相似文献
9.
Three new compounds, 1 – 3 , and 20 known compounds were isolated from the AcOEt and BuOH extract of edible Opuntia Milpa Alta. The petroleum ether extract was examined by GC and MS. A total of 26 compounds were identified, representing 95.6% of the total extract, phytosterol (36.03%) being the most abundant component, and polyunsaturated fatty acids (18.57%) represented the second largest group, followed by phytol (12.28%), palmitic acid, palmitate (13.54%), vitamin E (4.51%), and other compounds (7.47%). The effects of various extracts from edible Opuntia Milpa Alta (petroleum ether extract, AcOEt extract, BuOH extract, aqueous extract, H2O parts) and the positive control (received dimethylbiguanide) were tested on streptozotocin (STZ)‐induced diabetic mice. The results indicated that all the treatment groups could significantly decrease blood glucose levels in STZ‐induced diabetic mice compared to the model control group (P<0.01), except the aqueous extract group (P<0.05). Especially, the petroleum ether extract group and the positive control group showed remarkable decrease of blood glucose levels. Taken together, the results indicate that the petroleum ether extract is the major hypoglycemic part in edible Opuntia Milpa Alta, which may be developed to a potential natural hypoglycemic functional ingredient. 相似文献
10.
《Bioscience, biotechnology, and biochemistry》2013,77(7):1232-1236
The deodorizing mechanism of (-)-epigallocatechin gallate (EGCg), the main constituent of a green tea extract, against methyl mercaptan (CH3SH) was investigated. EGCg showed deodorizing activity against CH3SH by a chemical reaction between EGCg and CH3SH. The non-volatile reaction products were identified to be compounds introducing a methylthio and/or a methylsulfinyl group into the B ring of EGCg, and gaseous oxygen was necessary for deodorizing activity. From these results, it was assumed that the deodorizing mechanism of EGCg was due to the addition of a methylthio group to the ortho-quinone generated by atmospheric oxygen. It was also found that secondary compounds produced by the reaction between EGCg and CH3SH had a stronger deodorizing activity than that of EGCg itself. 相似文献
11.
Özlen Güzel-Akdemir Andrea Angeli Kübra Demir Claudiu T. Supuran 《Journal of enzyme inhibition and medicinal chemistry》2018,33(1):1299-1308
A small collection of 26 structurally novel thiazolidinone-containing compounds, without the well-known sulphonamide zinc-binding group, were synthesised and tested in enzyme inhibition assays against the tumour-associated hCA IX enzyme. Inhibition constants in the lower micromolar region (KI 25?μM) have been measured for 17 of the 26 compounds. Even though the KI values are relatively weak, the fact that they do not contain a sulphonamide moiety suggests that these compounds do not interact with the active site zinc ion. Therefore, docking studies and molecular dynamics simulations have been performed to suggest binding poses for these structurally novel inhibitors. 相似文献
12.
Twenty novel simple alkyl isocyanides derived from citronellol were synthesized and evaluated for their antifouling activity and toxicity against cypris larvae of the barnacle, Balanus amphitrite. The anti-barnacle activity of the synthesized isocyanides was in the EC50 range of 0.08–1.49 μg ml?1. Simple isocyanides containing a benzoate and chloro group showed the most potent anti-barnacle activity. In addition, none of the synthesized compounds showed significant toxicity and LC50 values were <10 μg ml?1. The LC50/EC50 ratios of almost all of the synthesized compounds were >102. The results indicate that these simple isocyanides are promising low-toxicity antifouling agents. 相似文献
13.
The toxicity of the α, β unsaturated carbonyl compounds (α, β UCCs) (patulin, penicillic acid, parasorbic acid, tulipalin and plumbagin) towards Pythium sp. group F (Van Der Plaat -Niterinks 1981) was neutralized by the addition of an excess of cysteine. This suggests that the mode of action of these compounds could be due to a binding of the α, βi UCCs to sulphydryl groups in enzymes or other macromolecules. Alcohol dehydrogenase (ADH), an enzyme with a sulphydryl group at the active site, was assayed spectrophotometrically and all the α, β UCCs inhibited ADH. 相似文献
14.
Mariusz Mojzych Paweł Tarasiuk Katarzyna Kotwica-Mojzych Muhammad Rafiq Sung-Yum Seo Michał Nicewicz 《Journal of enzyme inhibition and medicinal chemistry》2017,32(1):99-105
A new series of sulfonamide derivatives of pyrazolo[4,3-e][1,2,4]triazine with chiral amino group has been synthesized and characterized. The compounds were tested for their tyrosinase and urease inhibitory activity. Evaluation of prepared derivatives demonstrated that compounds (8b) and (8j) are most potent mushroom tyrosinase inhibitors whereas all of the obtained compounds showed higher urease inhibitory activity than the standard thiourea. The compounds (8a), (8f) and (8i) exhibited excellent enzyme inhibitory activity with IC50 0.037, 0.044 and 0.042?μM, respectively, while IC50 of thiourea is 20.9?μM. 相似文献
15.
The synthesis of four chiral NAD+ models 1 and their 1,4-dihydro analogs 2 is described. From the temperature dependence of the 1H-nmr spectra it is concluded that for these compounds two preferred conformations I and II, differing slightly in energy, exist. Both conformations are “folded” with the more or less parallel p-anisyl and pyridine groups mutually gauche, but in I the pyridine group is rotated by about 180° as compared with II, thus leading to a conspicuous difference in orientation of the substituent Z (NH2CO, C6H5NHSO2, (CH2)4NSO2, or (C4H8ON)SO2) in the pyridine ring toward the anisyl group. The most stable conformation (I) has Z closest to the center of the p-anisyl group. In 360-MHz spectra of the dihydropyridines at low temperature (−10°C), slow interconversion of I and II leads to the observation of an XY pattern for the C-4 methylene protons of the 1,4-dihydropyridine system. The anisochronity in this methylene group is caused mainly by the anisotropy of the neighboring p-anisyl group. 相似文献
16.
Glória PM Gut J Gonçalves LM Rosenthal PJ Moreira R Santos MM 《Bioorganic & medicinal chemistry》2011,19(24):7635-7642
A series of novel aza vinyl sulfones were designed, synthesized in good yields and evaluated as antiplasmodial agents. Tested compounds did not show activity against papain or the Plasmodium falciparum cysteine protease falcipain-2. However, a number of the new compounds effectively inhibited the in vitro development of P. falciparum. Compounds containing a squaramide group were the most active, with IC50 values between 0.95 and 4.5 μM, suggesting that these are potential lead compounds for the development of new antimalarial agents. 相似文献
17.
The production of vitamin B6 (B6) compounds with a cell-suspension of Achromobacter cycloclastes A.M.S. 6201 under various conditions were examined. An obvious accumulation of B6 compounds in the incubation medium with a cell-suspension of the organism harvested at the middle to later part of exponential phase of growth was observed. γ-Aminobutyric acid or β-alanine was found to stimulate the B6 production markedly, when they were added to the incubation mixture together with glycerol. Some discussion on the implication of these compounds as precursors of B6 was presented. 相似文献
18.
Design,Synthesis, and Antimycobacterial Evaluation of Novel Tetrahydroisoquinoline Hydrazide Analogs
Boddupalli Venkata Siva Kumar Yogesh Mahadu Khetmalis Adinarayana Nandikolla Banoth Karan Kumar Kevin Van Calster Sankaranarayanan Murugesan Davie Cappoen Kondapalli Venkata Gowri Chandra Sekhar 《化学与生物多样性》2023,20(2):e202200939
A series of novel 2-substituted-5,7-dichloro-1,2,3,4-tetrahydroisoquinoline-6-carbohydrazide were designed, synthesized and structures were confirmed by analytical methods, viz., 1H-NMR, 13C-NMR and Mass spectrometry. Synthesized derivatives were evaluated for their anti-mycobacterial activity against Mycobacterium tuberculosis (Mtb) H37Ra. Among all the evaluated compounds, 10A25 containing biphenyl moiety exhibited significant inhibition with IC50 4.7 μM. 10A19 , with an electron-withdrawing Iodo group in the ortho position of the phenyl exhibited significant anti-tubercular activity with IC50 8.8 μM. IC50 values of the remaining compounds ranged from 9.2 to 73.6 μM. Molecular docking study of the significantly active compound 10A25 was performed to determine the putative binding position of the test ligand at the active site of the selected target proteins Mycobacterium tuberculosis enoyl reductase (InhA) PDB – 4TZK and peptide deformylase PDB – 3E3U. A suitable single crystal for one of the active compounds, 10A12 , was generated and analysed to further confirm the structure of the compounds. 相似文献
19.
E.R. Milaeva O.A. Gerasimova Zhang Jingwei D.B. Shpakovsky S.A. Syrbu A.S. Semeykin O.I. Koifman E.G. Kireeva E.F. Shevtsova S.O. Bachurin N.S. Zefirov 《Journal of inorganic biochemistry》2008,102(5-6):1348
The novel metalloporphyrins (M = HH, Fe, Mn, Co, Cu, Zn) bearing 2,6-di-tert-butylphenol pendants as antioxidant substituents, and a long chain hydrocarbon palmitoyl group have been synthesized. The oxidation of compounds by PbO2 leads to the formation of the corresponding 2,6-di-tert-butylphenoxyl radicals studied by EPR. The activity of porphyrins in lipid peroxidation has been examined using (1) in vitro lipid peroxidation induced by tert-butylhydroperoxide in respiring rat liver mitochondria, (2) in vitro lipid peroxidation in liver homogenates of Wistar strain rats, and (3) a model process of peroxidation of (Z)-octadec-9-enic (oleic) acid as a structural fragment of lipids. The activity of these compounds depends dramatically on the nature of metal and might be changed from antioxidative (M = HH, Mn, Cu, Zn) to indifferent (M = Co), and to pro-oxidative one (M = Fe). The anti- or pro-oxidative action of these compounds may be derived from the concurrence between the involvement of 2,6-di-tert-butylphenol pendants acting as radical scavengers and redox active metal center promoting oxidation processes. The results of this study suggest that the polytopic compounds combining in one molecule 2,6-di-tert-butylphenol pendants, metalloporphyrin moiety, and a palmitoyl group, are membrane active compounds and might be studied in an effort to find novel pharmaceutical agents. 相似文献
20.
Yuxin An Xia Li Huanmei Sun Wenhai Bian Zijian Li Youyi Zhang Xinfeng Zhao Xiaohui Zheng 《Journal of molecular recognition : JMR》2015,28(10):628-634
The bioactive ingredients in Semen sinapis were rapidly screened by immobilized β2‐adrenoceptor (β2‐AR) and target‐directed molecular docking. The methods involved the attachment of β2‐AR using any amino group in the receptor, the simultaneous separation and identification of the retention compounds by high‐performance affinity chromatography; the binding mechanism of the interesting compound to the receptor was investigated by zonal elution and molecular docking. Sinapine in Semen sinapis was proved to be the bioactive compound that specifically binds to the immobilized receptor. The association constant of sinapine to β2‐AR was determined to be 1.36 × 105 M?1 with a value of 1.27 × 10?6 M for the number of binding sites. Ionic bond was believed to be the driving force during the interaction between sinapine and β2‐AR. It is possible to become a powerful alternative for rapid screening of bioactive compounds from a complex matrix such as traditional Chinese medicine and further investigation on the drug–receptor interaction. Copyright © 2015 John Wiley & Sons, Ltd. 相似文献