共查询到20条相似文献,搜索用时 31 毫秒
1.
Palaniappan Senthilkumar Murugesan Dinakaran Yogesh Chandraseakaran Perumal Yogeeswari Dharmarajan Sriram 《Archiv der Pharmazie》2009,342(2):100-112
Fifty one newer 1‐(cyclopropyl/2,4‐difluorophenyl/tert‐butyl)‐1,4‐dihydro‐8‐methyl‐6‐nitro‐4‐oxo‐7‐(substituted secondary amino)quinoline‐3‐carboxylic acids were synthesized from 1,3‐dichloro‐2‐methylbenzene and evaluated for in‐vitro antimycobacterial activities against Mycobacterium tuberculosis H37Rv (MTB), multi‐drug resistant Mycobacterium tuberculosis (MDR‐TB), and Mycobacterium smegmatis (MC2). Among the synthesized compounds, 1‐cyclopropyl‐1,4‐dihydro‐7‐(3,4‐dihydro‐6,7‐dimethoxyisoquinolin‐2(1H)‐yl)‐8‐methyl‐6‐nitro‐4‐oxoquinoline‐3‐carboxylic acid 9p was found to be the most active compound in vitro with a MIC value of 0.39 μM against MTB. Against MDR‐TB, compound 7‐(2‐carboxy‐5,6‐dihydroimidazo[1,2‐a]pyrazin‐7(8H)‐yl)‐1‐cyclopropyl‐1,4‐dihydro‐8‐methyl‐6‐nitro‐4‐oxoquinoline‐3‐carboxylic acid 9n was found to be the most active with a MIC value of 0.09 μM. 相似文献
2.
A series of novel 1H‐1,2,3‐triazole tethered isatin–moxifloxacin (MXF) hybrids 5a ‐ l with greater lipophilicity compared with the parent MXF were designed, synthesized and screened for their in vitro antimycobacterial activities against Mycobacterium tuberculosis (MTB) H37Rv and multidrug‐resistant MTB (MDR–MTB) as well as their cytotoxicity on the VERO cell line. All the synthesized hybrids (MIC: 0.025‐0.78 μg/ml) showed considerable activities against MTB H37Rv and MDR–MTB, and the most active conjugate 5c (MIC: 0.025 and 0.06 μg/ml) was 2 to >2048 times more potent in vitro than the three references MXF (MIC: 0.10 and 0.12 μg/ml), rifampicin (MIC: 0.39 and 32 μg/ml) and isoniazid (MIC: 0.05 and >128 μg/ml) against the two tested strains. All hybrids (CC50: 4‐64 μg/ml) were much more cytotoxic than the parent MXF (CC50: 128 μg/ml), but the most active hybrid 5c (CC50: 32 μg/ml) also displayed acceptable cytotoxicity, warranting further investigation. 相似文献
3.
Barbora Servusova‐Vanaskova Pavla Paterova Vladimir Garaj Jana Mandikova Jiri Kunes Lieve Naesens Petr Jílek Martin Dolezal Jan Zitko 《Chemical biology & drug design》2015,86(4):674-681
This work presents synthesis and antimicrobial evaluation of nineteen 6‐alkylamino‐N–phenylpyrazine‐2‐carboxamides. Antimycobacterial activity was determined against Mycobacterium tuberculosis H37Rv, M. kansasii and two strains of M. avium. Generally, the antimycobacterial activity increased with prolongation of simple alkyl chain and culminated in compounds with heptylamino substitution ( 3e , 4e ) with MIC = 5–10 μm against M. tuberculosis H37Rv. On the contrary, derivatives with modified alkyl chain (containing e.g. terminal methoxy or hydroxy group) as well as phenylalkylamino derivatives were mainly inactive. The most active compounds (with hexyl to octylamino substitution) were evaluated for their in vitro activity against drug‐resistant strains of M. tuberculosis and possessed activity comparable to that of the reference drug isoniazid. None of the tested compounds were active against M. avium. Some derivatives exhibited activity against Gram‐positive bacteria including methicillin‐resistant Staphylococcus aureus (best MIC = 7.8 μm ), while Gram‐negative strains as well as tested fungal strains were completely unsusceptible. Active compounds were tested for in vitro toxicity on various cell lines and in most cases were non‐toxic up to 100 μm . 相似文献
4.
A series of fluorinated 1,2,4‐triazolo[1,5‐a]pyrimidine‐6‐carboxylic acid derivatives was designed and synthesized as fluoroquinolone analogues. The synthesized compounds were screened against Mycobacterium tuberculosis H37Rv strain at 6.25 μg/mL concentration. Compound 4 , the 7‐oxo‐2‐(trifluoromethyl)‐4,7‐dihydro‐1,2,4‐triazolo[5,1‐a]pyrimidine‐6‐carboxylic acid was found to be a very potent inhibitor, being able to inhibit 92% growth of M. tuberculosis H37Rv at 6.25 μg/mL concentration. At the same time, it proofed to be nontoxic to mammalian cells (IC50 > 62.5 μg/mL in VERO cells). 相似文献
5.
Neha Agre Mariam Degani Antima Gupta Sanjib Bhakta Mukti Kanta Ray 《Archiv der Pharmazie》2019,352(9)
5‐Substituted‐6‐acetyl‐2‐amino‐7‐methyl‐5,8‐dihydropyrido[2,3‐d]pyrimidin‐4(3H)‐one derivatives were synthesized and evaluated against Mycobacterium tuberculosis H37Rv, Mycobacterium aurum, Escherichia coli, and Staphylococcus aureus as well as a human monocyte‐derived macrophage (THP‐1), and murine macrophage (RAW 264.7) cell lines to assess their antibacterial and cytotoxic potential, respectively. The compounds showed activity in the range of 1.95–125 µg/ml against M. tuberculosis but showed no activity against M. aurum, E. coli, and S. aureus, indicating selectivity towards slow‐growing mycobacterial pathogens. The compounds exhibited very low to no cytotoxicity up to 500 µg/ml concentration against eukaryotic cell lines. The most potent molecule, 2l , showed a minimum inhibitory concentration of 1.95 µg/ml against M. tuberculosis H37Rv and a selectivity index of >250 against both the eukaryotic cell lines. Furthermore, 2l showed moderate inhibition of whole‐cell mycobacterial drug‐efflux pumps when compared to verapamil, a known potent inhibitor of efflux pumps. Thus, derivative 2l was identified as an antituberculosis hit molecule, which could be used to yield more potent lead molecules. 相似文献
6.
Synthesis,biological evaluation,and molecular docking studies of novel 3‐aryl‐5‐(alkyl‐thio)‐1H‐1,2,4‐triazoles derivatives targeting Mycobacterium tuberculosis 下载免费PDF全文
Navnath D. Rode Amol D. Sonawane Laxman Nawale Vijay M. Khedkar Ramesh A. Joshi Anjali P. Likhite Dhiman Sarkar Rohini R. Joshi 《Chemical biology & drug design》2017,90(6):1206-1214
A small library of new 3‐aryl‐5‐(alkyl‐thio)‐1H‐1,2,4‐triazoles was synthesized and screened for the antimycobacterial potency against Mycobacterium tuberculosis H37Ra strain and Mycobacterium bovis BCG both in active and dormant stage. Among the synthesized library, 25 compounds exhibited promising anti‐TB activity in the range of IC500.03–5.88 μg/ml for dormant stage and 20 compounds in the range of 0.03–6.96 μg/ml for active stage. Their lower toxicity (>100 μg/ml) and higher selectivity (SI = >10) against all cancer cell lines screened make them interesting compounds with potential antimycobacterial effects. Furthermore, to rationalize the observed biological activity data and to establish a structural basis for inhibition of M. tuberculosis, the molecular docking study was carried out against a potential target MTB CYP121 which revealed a significant correlation between the binding score and biological activity for these compounds. Cytotoxicity and in vivo pharmacokinetic studies suggested that 1,2,4‐triazole analogues have an acceptable safety index, in vivo stability and bio‐availability. 相似文献
7.
Daniele Zampieri Maria Grazia Mamolo Erik Laurini Giuditta Scialino Elena Banfi Luciano Vio 《Archiv der Pharmazie》2009,342(12):716-722
2‐Aryl‐3‐(1H‐imidazol‐1‐yl and 1H‐1,2,4‐triazol‐1‐yl)‐1H‐indole derivatives were synthesized and tested for their in‐vitro antifungal and antimycobacterial activities. These indole derivatives were devoid of antifungal activity against the tested strains of Candida spp. Yet, they exhibited an interesting antitubercular activity against Mycobacterium tuberculosis reference strain H37Rv. 相似文献
8.
Venugopala K. Narayanaswamy Susanta K. Nayak Melendhran Pillay Renuka Prasanna Yacoob M. Coovadia Bharti Odhav 《Chemical biology & drug design》2013,81(2):219-227
A series of 2‐(substituted phenyl/benzyl‐amino)‐6‐(4‐chlorophenyl)‐5‐(methoxycarbonyl)‐4‐methyl‐3,6‐dihydropyrimidin‐1‐ium chlorides 7–13 and 15 was synthesized in their hydrochloride salt form. The title compounds were characterized by FT‐IR, NMR (1H and 13C) and elemental analysis. They were evaluated for their in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv, multidrug resistance tuberculosis and extensively drug resistance tuberculosis by agar diffusion method and tested for the cytotoxic action on peripheral blood mononuclear cells by MTT assay. Among all the tested compounds in the series, compounds 7 and 11 emerged as promising antitubercular agents at 16 μg/mL against multidrug resistance tuberculosis and over 64 μg/mL against extensively drug resistance tuberculosis. The conformational features and supramolecular assembly of the promising compounds 7 and 11 were determined by single crystal X‐ray study. 相似文献
9.
Synthesis and biological evaluation of 1,2,4‐triazole‐3‐thione and 1,3,4‐oxadiazole‐2‐thione as antimycobacterial agents 下载免费PDF全文
Amol D. Sonawane Navnath D. Rode Laxman Nawale Rohini R. Joshi Ramesh A. Joshi Anjali P. Likhite Dhiman Sarkar 《Chemical biology & drug design》2017,90(2):200-209
Resistance among dormant mycobacteria leading to multidrug‐resistant and extremely drug‐resistant tuberculosis is one of the major threats. Hence, a series of 1,2,4‐triazole‐3‐thione and 1,3,4‐oxadiazole‐2‐thione derivatives ( 4a–5c ) have been synthesized and screened for their antitubercular activity against Mycobacterium tuberculosis H37Ra (H37Ra). The triazolethiones 4b and 4v showed high antitubercular activity (both MIC and IC50) against the dormant H37Ra by in vitro and ex vivo. They were shown to have more specificity toward mycobacteria than other Gram‐negative and Gram‐positive pathogenic bacteria. The cytotoxicity was almost insignificant up to 100 μg/ml against THP‐1, A549, and PANC‐1 human cancer cell lines, and solubility was high in aqueous solution, indicating the potential of developing these compounds further as novel therapeutics against tuberculosis infection. 相似文献
10.
Design,Synthesis, and Antimycobacterial Activity of Novel Theophylline‐7‐Acetic Acid Derivatives With Amino Acid Moieties 下载免费PDF全文
Georgi Stavrakov Violeta Valcheva Yulian Voynikov Irena Philipova Mariyana Atanasova Spiro Konstantinov Plamen Peikov Irini Doytchinova 《Chemical biology & drug design》2016,87(3):335-341
The theophylline‐7‐acetic acid (7‐TAA) scaffold is a promising novel lead compound for antimycobacterial activity. Here, we derive a model for antitubercular activity prediction based on 14 7‐TAA derivatives with amino acid moieties and their methyl esters. The model is applied to a combinatorial library, consisting of 40 amino acid and methyl ester derivatives of 7‐TAA. The best three predicted compounds are synthesized and tested against Mycobacterium tuberculosis H37Rv. All of them are stable, non‐toxic against human cells and show antimycobacterial activity in the nanomolar range being 60 times more active than ethambutol. 相似文献
11.
Karel Waisser Josef Matyk Jirí Kuneš Rafael Doležal Jarmila Kaustová Hans‐Martin Dahse 《Archiv der Pharmazie》2008,341(12):800-803
A series of 6‐chloro‐3‐(4‐alkylphenyl)‐4‐thioxo‐2H‐1,3‐benzoxazine‐2(3H)‐ones, 7‐chloro‐3‐(4‐alkylphenyl)‐4‐thioxo‐2H‐1,3‐benzoxazine‐2(3H)‐ones, 6‐bromo‐3‐(4‐alkylphenyl)‐4‐thioxo‐2H‐1,3‐benzoxazine‐2(3H)‐ones, 6,8‐dibromo‐3‐(4‐alkylphenyl)‐4‐thioxo‐2H‐1,3‐benzoxazine‐2(3H)‐ones, 6‐chloro‐3‐(4‐alkylphenyl)‐2H‐1,3‐benzoxazine‐2,4(3H)‐dithiones, 7‐chloro‐3‐(4‐alkylphenyl)‐2H‐1,3‐benzoxazine‐2,4(3H)‐dithiones, 6‐bromo‐3‐(4‐alkylphenyl)‐2H‐1,3‐benzoxazine‐2,4(3H)‐dithiones and 6,8‐dibromo‐3‐(4‐alkylphenyl)‐2H‐1,3‐benzoxazine‐2,4(3H)‐dithiones was synthesized. The compounds exhibited in‐vitro activity against Mycobacterium tuberculosis, M. kansasii (two strains), and M. avium. 6‐bromo‐3‐(4‐propylphenyl)‐4‐thioxo‐2H‐1,3‐benzoxazin‐2(3H)‐one and 6‐bromo‐3‐(4‐propylphenyl)‐2H‐1,3‐benzoxazin‐2,4(3H)‐dithione are the most active compounds against M. tuberculosis. The activity is similar to isoniazid (INH). The compounds under study have a broad spectrum of activity against potential pathogenic strains. The replacement of the oxo group by thioxo group of 3‐(4‐alkylphenyl)‐2H‐1,3‐benzoxazine‐2,4(3H)‐diones often led to an improvement in the antimycobacterial activity against M. tuberculosis. 相似文献
12.
Li Wang Xing Zheng Hong‐Lin Xiang Xiao‐Hua Fu Jian‐Guo Cao 《Clinical and experimental pharmacology & physiology》2009,36(12):e90-e95
1. Genistein is known to protect the vascular endothelium. However, genistein exhibits poor bioavailability, which limits its use in the treatment of cardiovascular diseases. 7‐Difluoromethyl‐5,4′‐dimethoxygenistein (dFMGEN), prepared by the difluoromethylation and alkylation of genistein, is a new active chemical entity. The protective effects of dFMGEN against vascular endothelial injury caused by oxidative stress were investigated in the present study. 2. Human umbilical vein endothelial cells were treated with either genistein (10 μmol/L) or various concentrations of dFMGEN (0.1, 0.3, 1, 3 and 10 μmol/L) for 30 min before exposure to 1 mmol/L H2O2 for 24 h. The generation of reactive oxygen species (ROS) was assessed by fluorescence flow cytometry, the release of lactate dehydrogenase (LDH) was examined by biochemical assay, cell viability was measured by the 3‐(4,5‐dimethyl‐2 thiazoyl)‐2,5‐diphenyl‐2H‐tetrazolium bromide assay, cell apoptosis was detected by flow cytometry and the expression of caspase 3 was examined by western blot analysis. 3. Pretreatment with 0.1, 0.3, 1, 3 and 10 μmol/L dFMGEN decreased the generation of ROS and the release of LDH in H2O2‐exposed vascular endothelial cells, enhanced cell viability in a concentration‐dependent manner over the concentration range 0.1–10 μmol/L, suppressed H2O2‐induced apoptosis of vascular endothelial cells and downregulated the expression of caspase 3. The protective effect of 10 μmol/L dFMGEN against oxidative stress‐induced endothelial injury was stronger than that of 10 μmol/L genistein. 4. The results of the present study suggest that dFMGEN can protect against vascular endothelial injury caused by oxidative stress. 相似文献
13.
Neha Agre Mihir Khambete Arundhati Maitra Antima Gupta Tulika Munshi Sanjib Bhakta Mariam Degani 《Chemical biology & drug design》2020,95(1):192-199
We report the biological evaluation of 5‐(5‐nitrothiophen‐2‐yl)‐4,5‐dihydro‐1H‐pyrazole derivatives against bacteria, eukaryotic cell lines and the assessment of their mechanisms of action to determine their prospects of being developed into potent antituberculosis agents. The compounds were evaluated for their antibacterial property against Mycobacterium tuberculosis H37Rv, multidrug‐resistant M. tuberculosis, Mycobacterium bovis BCG, Mycobacterium aurum, Escherichia coli, and Staphylococcus aureus using high‐throughput spot‐culture growth inhibition assay. They were found to be selective toward slow‐growing mycobacteria and Gram‐positive bacteria. In M. bovis BCG, they exhibited a bactericidal mode of action. Cytotoxicity was assessed in human THP‐1 and murine RAW 264.7 cell lines, and the compounds showed a lower cytotoxicity potential when compared with their antibacterial activity. They were found to be excellent whole‐cell efflux pump inhibitors of the mycobacterial surrogate M. aurum, performing better than known efflux pump inhibitor verapamil. The 5‐nitrothiophene moiety was identified for the first time as a prospective inhibitor scaffold of mycobacterial arylamine N‐acetyltransferase enzyme, which is the key enzyme in metabolizing isoniazid, a first‐line antituberculosis drug. The two aforementioned findings make the compounds potential hits in the development of adjunctive tuberculosis therapy. 相似文献
14.
Claudia Vergelli Agostino Cilibrizzi Letizia Crocetti Alessia Graziano Vittorio Dal Piaz Baojie Wan Yuehong Wang Scott Franzblau Maria Paola Giovannoni 《Drug development research》2013,74(3):162-172
Preclinical Research |
15.
Suresh Kumar Neeraj Upmanyu Obaid Afzal Sandhya Bawa 《Chemical biology & drug design》2014,84(5):522-530
A series of 1‐(substituted‐phenyl)‐1‐[(2‐chloroquinolin‐3‐yl)methyl]thiocarbamide and 1‐(substituted‐phenyl)‐1‐[(2‐chloroquinolin‐3‐yl)methyl]methylthiocarbamide derivatives was synthesized as antitubercular agent. The structure of quinolinyl amines and their thiocarbamide derivatives were established on the basis of IR, 1H and 13C‐NMR and mass spectral data. All the compounds were tested in vitro for antimycobacterial activity against Mycobacterium tuberculosis (ATCC‐25177) in Lowenstein‐Jensen medium by well diffusion method and MIC by twofold serial dilution method. Results of the antitubercular screening revealed that compounds showed moderate to good antitubercular activity. Compound having two halogens in the phenyl rings viz. 3g , 3h , 4g, and 4h exhibited MIC of 50 μg/mL. The computational parameters relevant to absorption and permeation of target compounds were also calculated and found to be well correlated with antitubercular activity. 相似文献
16.
The re‐emergence of tuberculosis (TB) as a global health problem over the past few decades, accompanied by the rise of drug‐resistant strains of Mycobacterium tuberculosis, emphasizes the need for the discovery of new therapeutic drugs against this disease. The emerging serious problem both in terms of TB control and clinical management prompted us to synthesize a novel series of N‐[2‐(substituted aryl)‐3‐chloro‐4‐oxoazetidin‐1‐yl]‐2‐(pyrazin‐2‐yloxy)acetamide, 6‐(substituted aryl)‐3‐[(pyrazin‐2‐yloxy)methyl][1,2,4]triazolo[3,4‐b][1,3,4]thiadiazole, and N‐[6‐({2‐[(pyrazin‐2‐yloxy)acetyl] hydrazino}sulfonyl)‐2‐methyl‐4‐oxo‐1,4‐dihydroquinazolin‐3(2H)yl]‐substituted aryl sulfonamides. The compounds were synthesized using the appropriate synthetic route. All synthesized compounds were assayed in vitro for antimycobacterial activity against the H37 Rv strain of Mycobacterium tuberculosis. The minimum inhibitory concentration (MIC) was determined for the test compounds as well as for the reference standards. The compound which exhibited good antimycobacterial activity contains the substituents fluorine and methoxy. These electron‐withdrawing or ‐donating substituents amend the lipophilicity of the test compounds which, in turn, alter the permeability across the bacterial cell membrane. Compounds 28 , 37 , and 43 showed good antimycobacterial activity while compound 51 showed a promising antimycobacterial activity. 相似文献
17.
Ranjan C. Khunt Vijay M. Khedkar Evans C. Coutinho 《Chemical biology & drug design》2013,82(6):669-684
Frequency of tuberculosis is progressively increasing worldwide. New emerging strains of bacilli that are emerging are resistant to the currently available drugs which make this issue more alarming. In this regard, a series of substituted quinolinyl chalcones, quinolinyl pyrimidines, and pyridines were synthesized and evaluated for their antitubercular activity in vitro against Mycobacterium tuberculosis H37RV. To establish the role of the 2‐chloroquinoline nucleus as a pharmacophoric group and study its influence on the antimycobacterial activity, a 3D‐QSAR study based on CoMFA and CoMSIA was undertaken on this set of 2‐chloroquinoline derivatives. Statistically significant models that are able to well correlate the antimycobacterial activity with the chemical structures of the 2‐chloroquinolines have been developed. The contour maps resulting from the best CoMFA and CoMSIA models were used to identify the structural features relevant to the biological activity in this series of analogs. Further analysis of these interaction‐field contour maps also showed a high level of internal consistency. The information obtained from the field 3‐D contour maps may be fruitfully utilized in the design of more potent 2‐chloroquinoline‐based analogs as potential antitubercular candidates. 相似文献
18.
Peng Yao Xin Zhai Dong Liu Bao Hui Qi Hai Liang Tan Yong Cai Jin Ping Gong 《Archiv der Pharmazie》2010,343(1):17-23
We herein disclose a series of novel diaryl urea derivatives possessing a 4H‐pyrido[1,2‐a]pyrimidin‐4‐one group as novel potent anticancer compounds. The structures were confirmed by IR, 1H‐NMR, and MS. All the compounds were screened for their antiprofilerative activity agaist the human breast cancer cell line (MDA‐MB‐231). The pharmacological results indicated that most of the compounds showed moderate activity. The best of this series is compound 4c (IC50 = 0.7 μmol/L), with a potency 3.6‐fold higher than Sorafenib (IC50 = 2.5 μmol/L), which was approved in 2005. 相似文献
19.
Cardoso SH Barreto MB Lourenço MC Henriques Md Candéa AL Kaiser CR de Souza MV 《Chemical biology & drug design》2011,77(6):489-493
The present article describes a series of 21 N ′‐benzylidene‐2‐oxo‐2H‐chromene‐3‐carbohydrazides 4a–4v , which were synthesized and evaluated for their cell viabilities in non‐infected and Mycobacterium bovis Bacillus Calmette–Guerin‐infected macrophages. Subsequently, the non‐cytotoxic compounds 4c, 4g, 4h, 4j, 4l and 4t were assessed against Mycobacterium tuberculosis ATCC 27294 using the microplate Alamar Blue assay and the activity expressed as the minimum inhibitory concentration in μg/mL. These compounds exhibited a significant activity (50–100 μg/mL) when compared to the first‐line drugs, such as pyrazinamide (PZA >100 μg/mL). These results could be considered a good starting point for further studies to develop new lead compounds to treat multidrug‐resistant tuberculosis. 相似文献
20.
Tolga R. Aydos Melih O. Babaoglu M. Oguz Guc Mustafa Ilhan 《Drug development research》1999,46(2):148-154
The inhibitory effect of the selective M3 musarinic acetylcholine receptor antagonist, 4‐diphenylacetoxy‐N‐methylpiperidine methobromide (4‐DAMP, 0.1–10 μM) on nicotine (100 μM)‐induced nitrergic relaxation was investigated in comparison to d‐tubocurarine (0.1–10 μM) and hexamethonium (0.1–10 μM) by using phenylephrine (1 μM)‐precontracted rat anococcygeus muscles in vitro. Nicotine produced a 60.1± 2.4% (n = 40) inhibition of phenylephrine precontractions. But this relaxant response was at a significantly lower magnitude of 20.2± 4.6% (n = 18, P < 0.01 vs. control) in the presence of the nitric oxide synthase (NOS) blocker NG‐nitro‐L ‐arginine methyl ester (L ‐NAME, 30 μM), and it was 26.5± 5.5% (n = 8, P < 0.01 vs. control) in the presence of the soluble guanylate cyclase inhibitor methylene blue (30 μM). However, aminoguanidine (100 μM), a relatively selective blocker of the inducible nitric oxide synthase (iNOS), had no significant effect. Similarly, other iNOS inhibitors such as dexamethasone (5 mg/kg) or L ‐canavanine (100 mg/kg) did not modify contractile nor relaxant responses when they were given in vivo, concomitantly with Escherichia coli endotoxin (1 mg/kg, ip) 4 h before the isolation of the tissues. 4‐DAMP, hexamethonium, and d‐tubocurarine inhibited nicotine‐induced relaxation in a concentration‐dependent manner with the following order of potency: 4‐DAMP > hexamethonium > d‐tubocurarine with IC50 values being 0.47± 0.04 μM, 0.75± 0.06 μM, and 1.02± 0.05 μM, respectively. Therefore, it was concluded that the selective M3 muscarinic acetylcholine receptor antagonist 4‐DAMP also possesses potent antagonistic action on nicotinic receptors of peripheral nitrergic neurons that innervate the rat anococcygeus muscle. Drug Dev. Res. 46:148–154, 1999. © 1999 Wiley‐Liss, Inc. 相似文献