共查询到20条相似文献,搜索用时 31 毫秒
1.
Barbora Servusová Jana Vobicková Pavla Paterová Vladimír Kubíček Jiří Kuneš Martin Doležal Jan Zitko 《Bioorganic & medicinal chemistry letters》2013,23(12):3589-3591
To develop new potential antimycobacterial drugs, a series of pyrazinamide derivatives was designed, synthesized and tested for their ability to inhibit the growth of selected mycobacterial strains (Mycobacterium tuberculosis H37Rv, Mycobacterium kansasii and two strains of Mycobacterium avium). This Letter is focused on binuclear pyrazinamide analogues containing the –CONH–CH2– bridge, namely on N-benzyl-5-chloropyrazine-2-carboxamides with various substituents on the phenyl ring and their comparison with some analogously substituted 5-chloro-N-phenylpyrazine-2-carboxamides. Compounds from the N-benzyl series exerted lower antimycobacterial activity against M. tuberculosis H37Rv then corresponding anilides, however comparable with pyrazinamide (12.5–25 μg/mL). Remarkably, 5-chloro-N-(4-methylbenzyl)pyrazine-2-carboxamide (8, MIC = 3.13 μg/mL) and 5-chloro-N-(2-chlorobenzyl)pyrazine-2-carboxamide (1, MIC = 6.25 μg/mL) were active against M. kansasii, which is naturally unsusceptible to PZA. Basic structure–activity relationships are presented. 相似文献
2.
Vasudeva Rao Avupati Rajendra Prasad Yejella Venkateswara Rao Parala Kishore Naidu Killari Venkata Madhava Reddy Papasani Prasad Cheepurupalli Venkateswara Rao Gavalapu Bhavani Boddeda 《Bioorganic & medicinal chemistry letters》2013,23(21):5968-5970
A series of some novel 1,3,5-triazine–Schiff base conjugates (1–32) have been synthesized and evaluated for their in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv using Alamar Blue assay and the activity expressed as the minimum inhibitory concentration (MIC) in μg/mL. Compounds 4 (4-Methoxy-6-methyl-N-(3,4,5-trimethoxybenzylidene)-1,3,5-triazin-2-amine), 11 (4-Methoxy-6-methyl-N-(2-hydroxy-3-bromo-5-chloro-benzylidene)-1,3,5-triazin-2-amine) and 24 (4-Methoxy-6-methyl-N-(1-(2,5-dihydroxyphenyl)ethylidene)-1,3,5-triazin-2-amine) exhibited a significant activity at 3.125, 6.25 and 6.25 μg/mL, respectively, when compared with the antitubercular drugs such as ethambutol (3.125 μg/mL), pyrazinamide (6.25 μg/mL) and streptomycin (6.25 μg/mL) and it could be a potential starting point to develop new lead compounds in the fight against Mycobacterium tuberculosis H37Rv. 相似文献
3.
M. Mujahid R.G. Gonnade P. Yogeeswari D. Sriram M. Muthukrishnan 《Bioorganic & medicinal chemistry letters》2013,23(5):1416-1419
A series of 21 new amino alcohol fused spirochromone conjugates have been synthesized, characterized with analytical data and evaluated their antimycobacterial activity against Mycobacterium tuberculosis (virulent strain H37Rv) in vitro. Some of the compounds exerted significant inhibition, in particular, compound 4f found to be the most potent derivative exhibiting MIC = 3.13 μg/mL. 相似文献
4.
《Bioorganic & medicinal chemistry letters》2014,24(17):4166-4170
In search of potential therapeutics for tuberculosis, we describe here the synthesis and in vitro antitubercular activity of a novel series of thiazolone piperazine tetrazole derivatives. Among all the synthesized derivatives, four compounds (10, 14, 20 and 33) exhibited more potent activity (MIC = 3.08, 3.01, 2.62 and 2.51 μM) than ethambutol (MIC = 9.78 μM) and pyrazinamide (MIC = 101.53 μM) against Mycobacterium tuberculosis. Furthermore, they displayed no toxicity against Vero cells (C1008) and mouse bone marrow derived macrophages (MBMDMϕ). These investigated analogues have emerged as possible lead molecule to enlarge the scope of the study. 相似文献
5.
Synthesis and evaluation of a novel series of pseudo-cinnamic derivatives as antituberculosis agents
Georges Koumba Yoya Florence Bedos-Belval Patricia Constant Hubert Duran Mamadou Daffé Michel Baltas 《Bioorganic & medicinal chemistry letters》2009,19(2):341-343
In an effort to develop potent new antituberculous drugs effective against Mycobacterium tuberculosis, we have prepared series of cinnamic derivatives (thioesters and amides) with 4-hydroxy and 4-alkoxy groups and investigated the in vitro activities of these compounds. Among them some displayed a good in vitro antibacterial activity, such as (E)-N-(2-acetamidoethyl)-3-{4-[(E)-3,7-dimethylocta-2,6-dienyloxy]phenyl}acrylamide 4b that showed a minimum inhibitory concentration of 0.1 μg/mL (0.26 μM) against M. tuberculosis H37Rv. 相似文献
6.
Hunsur Nagendra Nagesh Kalaga Mahalakshmi Naidu Damarla Harika Rao Jonnalagadda Padma Sridevi Dharmarajan Sriram Perumal Yogeeswari Kondapalli Venkata Gowri Chandra Sekhar 《Bioorganic & medicinal chemistry letters》2013,23(24):6805-6810
Focus in this Letter is made to design and synthesize a series of nineteen new 6-(4-((substituted-1H-1,2,3-triazol-4-yl)methyl)piperazin-1-yl)phenanthridine analogues employing click chemistry and evaluated for their anti-tubercular activity against Mycobacterium tuberculosis H37Rv. Among the tested compounds, 7f and 7j exhibited good activity (MIC = 3.125 μg/mL), while 8a displayed excellent activity (MIC = 1.56 μg/mL) against the growth of M. tuberculosis H37Rv. In addition, 7f, 7j and 8a compounds were subjected to cytotoxic studies against mouse macrophage (RAW264.7) cell lines and the selectivity index values are >15 indicating suitability of compounds for further drug development. 相似文献
7.
《Bioorganic & medicinal chemistry letters》2014,24(8):1912-1917
Tuberculosis remains a global public health problem in recent years. To develop novel type of potential antitubercular agents, twelve novel dihydroartemisinin–fluoroquinolone (DHA–FQ) conjugates (three types of molecules) were gradually designed and conveniently synthesized. All the newly synthesized conjugates were well characterized and evaluated against different Mycobacterium tuberculosis strains in vitro. The screening results showed that five DHA–FQ conjugates were active toward M. tuberculosis H37Rv, and compound 3a exhibited the strongest inhibitory activity (MIC = 0.0625 μg/mL), which was comparable to the positive control Moxifloxacin and even stronger than Ofloxacin. Conjugates 2a and 3a also displayed comparable activities against various clinically isolated sensitive and resistant M. tuberculosis strains (MIC = 0.125–16 μg/mL) to Moxifloxacin. All target compounds possessed selective anti-M. tuberculosis ability. Preliminary structure–activity relationship demonstrated that short linker between DHA and FQ was favorable for strong antitubercular activity. This study provides a new clue for the development of novel antitubercular lead molecules. 相似文献
8.
《Bioorganic & medicinal chemistry》2016,24(5):1023-1031
Tuberculosis is a serious infectious disease caused by human pathogen bacteria Mycobacterium tuberculosis. Bacterial drug resistance is a very significant medical problem nowadays and development of novel antibiotics with different mechanisms of action is an important goal of modern medical science. Leucyl-tRNA synthetase (LeuRS) has been recently clinically validated as antimicrobial target. Here we report the discovery of small-molecule inhibitors of M. tuberculosis LeuRS. Using receptor-based virtual screening we have identified six inhibitors of M. tuberculosis LeuRS from two different chemical classes. The most active compound 4-{[4-(4-Bromo-phenyl)-thiazol-2-yl]hydrazonomethyl}-2-methoxy-6-nitro-phenol (1) inhibits LeuRS with IC50 of 6 μM. A series of derivatives has been synthesized and evaluated in vitro toward M. tuberculosis LeuRS. It was revealed that the most active compound 2,6-Dibromo-4-{[4-(4-nitro-phenyl)-thiazol-2-yl]-hydrazonomethyl}-phenol inhibits LeuRS with IC50 of 2.27 μM. All active compounds were tested for antimicrobial effect against M. tuberculosis H37Rv. The compound 1 seems to have the best cell permeability and inhibits growth of pathogenic bacteria with IC50 = 10.01 μM and IC90 = 13.53 μM. 相似文献
9.
Xuelian Zhang Yanwei Hu Shudan Chen Rusong Luo Jun Yue Ying Zhang Wenhu Duan Honghai Wang 《Bioorganic & medicinal chemistry letters》2009,19(21):6074-6077
In order to identify new and potent candidate drugs to treat tuberculosis, a library of compounds was screened, and (S,S)-N,N′-bis-[3-(2,2′,6,6′-tetramethylbenzhydryloxy)-2-hydroxy-propyl]-ethylenediamine (S2824) was identified as a hit in the screen. This research discusses our efforts to synthesize and test 30 analogs of this hit for activity against Mycobacterium tuberculosis. Two compounds with homopiperazine ring possess high in vitro activity against drug sensitive and resistant M. tuberculosis with MICs 0.78–3.13 μg/mL (or 1.22–4.88 μM). 相似文献
10.
Fátima M.F. Vergara Maria das G.M.O. Henriques André L.P. Candea Jim L. Wardell Marcus V.N. De Souza 《Bioorganic & medicinal chemistry letters》2009,19(17):4937-4938
A series of 11 α,ω-diaminoalkanes, (H2N(CH2)nNH2, n = 2–12) have been evaluated for their in vitro antibacterial activity against Mycobacterium tuberculosis H37Rv. Compounds, (H2N(CH2)nNH2, n = 9–12), exhibited a very good activities in the range 2.50–3.12 μg/mL, which can be compared with that of the first line drug, ethambutol (3.12 μg/mL). These results and a preliminary QSAR study can be considered an important start point for the rational design of new leads for anti-TB compounds. 相似文献
11.
Daniele Castagnolo Fabrizio Manetti Marco Radi Beatrice Bechi Mafalda Pagano Alessandro De Logu Rita Meleddu Manuela Saddi Maurizio Botta 《Bioorganic & medicinal chemistry》2009,17(15):5716-5721
Two series of novel rigid pyrazolone derivatives were synthesized and evaluated as inhibitors of Mycobacterium tuberculosis (MTB), the causative agent of tuberculosis. Two of these compounds showed a high activity against MTB (MIC = 4 μg/mL). The newly synthesized pyrazolones were also computationally investigated to analyze if their properties fit the pharmacophoric model for antitubercular compounds previously built by us. The results are in agreement with those reported by us previously for a class of pyrazole analogues and confirm the fundamental role of the p-chlorophenyl moiety at C4 in the antimycobacterial activity. 相似文献
12.
Esther Vicente Silvia Pérez-Silanes Lidia M. Lima Saioa Ancizu Asunción Burguete Beatriz Solano Raquel Villar Ignacio Aldana Antonio Monge 《Bioorganic & medicinal chemistry》2009,17(1):385-389
New series of 3-phenylquinoxaline 1,4-di-N-oxide with selective activity against Mycobacterium tuberculosis have been prepared and evaluated. Thirty-four of the seventy tested compounds showed an MIC value less than 0.2 μg/mL, a value on the order of the MIC of rifampicin. Furthermore, 45% of the evaluated derivatives showed a good in vitro activity/toxicity ratio. The most active and selective compounds carry a fluorine atom in the quinoxaline 7-position or in the phenyl substituent para-position. In conclusion, the potency, low cytotoxicity and selectivity of these compounds make them valid lead compounds for synthesizing new analogues, particularly compound 7-methyl-3-(4’-fluoro)phenylquinoxaline-2-carbonitrile 1,4-di-N-oxide (MIC <0.2 μg/mL and SI >500). 相似文献
13.
《Bioorganic & medicinal chemistry letters》2014,24(7):1695-1697
This Letter reports the synthesis and evaluation of some thiazolylhydrazone derivatives for their in vitro antimycobacterial activities against Mycobacterium tuberculosis H37Rv. The cytotoxic activities of all compounds were also evaluated. The compounds exhibited promising antimycobacterial activity with MICs of 1.03–72.46 μM and weak cytotoxicity (8.9–36.8% at 50 μg/mL). Among them, 1-(4-(1H-1,2,4-triazol-1-yl)benzylidene)-2-(4-(4-nitrophenyl)thiazol-2-yl)hydrazine 10 was found to be the most active compound (MIC of 1.03 μM) with a good safety profile (16.4% at 50 μg/mL). Molecular modeling studies were done to have an idea for the mechanism of the action of the target compounds. According the docking results it can be claimed that these compounds may bind most likely to TMPK than InhA or CYP121. 相似文献
14.
Sandra Gemma Luisa Savini Maria Altarelli Pierangela Tripaldi Luisa Chiasserini Salvatore Sanna Coccone Vinod Kumar Caterina Camodeca Giuseppe Campiani Ettore Novellino Sandra Clarizio Giovanni Delogu Stefania Butini 《Bioorganic & medicinal chemistry》2009,17(16):6063-6072
A series of 4-quinolylhydrazones was synthesized and tested in vitro against Mycobacterium tuberculosis. At a concentration of 6.25 μg/mL, most of the newly synthesized compounds displayed 100% inhibitory activity against M. tuberculosis in cellular assays. Further screening allowed the identification of very potent antitubercular agents. Compound 4c was also tested in a time-course experiment and against mtb clinical isolates, displaying interesting results. 相似文献
15.
Matthew L. Read Morten Brændvang Pedro O. Miranda Lise-Lotte Gundersen 《Bioorganic & medicinal chemistry》2010,18(11):3885-3897
Pyrimidine analogs of antimycobacterial 6-aryl-9-benzylpurines have been synthesized and screened for antibacterial activity against Mycobacterium tuberculosis H37Rv in vitro. Several active compounds were identified and the best results were observed for 5-formamidopyrimidines. These compounds generally displayed IC90 values ≤1 μg/mL, and they exhibited low toxicity towards mammalian cells. Imidazolylpyrimidines, which may be regarded as fleximer analogs of the parent purines, were also synthesized and one of them was found to be quite a potent inhibitor of M. tuberculosis (IC90 14 μg/mL). 相似文献
16.
Chao Huang Sheng-Jiao Yan Neng-Qin He Ya-Juan Tang Xing-Hong Wang Jun Lin 《Bioorganic & medicinal chemistry letters》2013,23(8):2399-2403
A series of polyhalo isophthalonitrile derivatives (3 and 4) that incorporate a variety of substituents at the 2-, 4-, 5- and/or 6-positions of the isophthalonitrile moieties have been designed and synthesized. These derivatives were evaluated for their antimicrobial activity against Staphylococcus aureus, Bacillus cereus (Gram-positive bacteria), Escherichia coli, Pseudomonas aeruginosa (Gram-negative bacteria); and Candida albicans (Fungi). Compounds 3 and 4 showed stronger inhibition of Gram-positive bacteria and fungi growth, and the antimicrobial ability of compound 3j (a 4-(benzylamino)-5-chloro-2,6-difluoro analog, MIC[SA] = 0.5 μg/mL; MIC[BC] = 0.4 μg/mL; MIC[CA] = 0.5 μg/mL) were close to nofloxacin and fluconazole and identified as the most potent antimicrobial agents in the series. The preliminary analysis of structure–activity relationships is also discussed. 相似文献
17.
Mohamed Ashraf Ali Jeyabalan Govinda Samy Elumalai Manogaran Velmurugan Sellappan Mohamed Zaheen Hasan Mohamed Jawed Ahsan Suresh Pandian Mohammad ShaharYar 《Bioorganic & medicinal chemistry letters》2009,19(24):7000-7002
In present investigation, a series of substituted phenyl-5,6-dimethoxy-1-oxo-2,5-dihydro-1H-2-indenylmethanone analogues were synthesized and were evaluated for antimycobacterial activity against Mycobacterium tuberculosis H37Rv and INH resistant M. tuberculosis. All the newly synthesized compounds were showing moderate to high inhibitory activities. The compound 5,6-dimethoxy-1-oxo-2,5-dihydro-1H-2-indenyl-4-fluorophenylmethanone (5g) was found to be the most promising compounds active against M. tuberculosis H37Rv and isoniazid (INH) resistant M. tuberculosis with Minimum inhibitory concentration 0.10 and 0.10 μM. 相似文献
18.
Deepak Kumar K. Kranthi Raj MaiAnn Bailey Torey Alling Tanya Parish Diwan S. Rawat 《Bioorganic & medicinal chemistry letters》2013,23(5):1365-1369
A series of C-(3-aminomethyl-cyclohexyl)-methylamine derivatives were synthesized and evaluated for their antitubercular activity. Some of the compounds exhibited potent activity against Mycobacterium tuberculosis H37Rv. One of the compound having t-butyl at para position of the benzene ring showed excellent activity even better than the standard drug ethambutol with MIC value 1.1 ± 0.2 μM. The time-kill kinetics study of two most active compounds showed rapid killing of the M. tuberculosis within 4 days. Additionally atom-based quantitative structure–activity relationship (QSAR) model was developed that gave a statistically satisfying result (R2) = 0.92, Q2 = 0.75, Pearson-R = 0.96 and effectively predicts the anti-tuberculosis activity of training and test set compounds. 相似文献
19.
Eduard R. Shmalenyuk Larisa N. Chernousova Inna L. Karpenko Sergey N. Kochetkov Tatiana G. Smirnova Sofia N. Andreevskaya Alexander O. Chizhov Olga V. Efremenkova Ludmila A. Alexandrova 《Bioorganic & medicinal chemistry》2013,21(17):4874-4884
Two sets of pyrimidine nucleoside derivatives bearing extended alkyloxymethyl or alkyltriazolidomethyl substituents at position 5 of the nucleobase were synthesized and evaluated as potential antituberculosis agents. The impact of modifications at 3′- and 5′-positions of the carbohydrate moiety on the antimycobacterial activity and cytotoxicity was studied. The highest effect was shown for 5-dodecyloxymethyl-2′-deoxyuridine, 5-decyltriazolidomethyl-2′-deoxyuridine, and 5-dodecyltriazolidomethyl-2′-deoxycytidine. They effectively inhibited the growth of two Mycobacterium tuberculosis strains in vitro, laboratory H37Rv (MIC99 = 20, 10, and 20 μg/mL, respectively) and clinical MDR MS-115 resistant to five top antituberculosis drugs (МIC99 = 50, 10, and 10 μg/mL, respectively). 相似文献
20.
《Bioorganic & medicinal chemistry》2014,22(2):728-737
A series of 27 salicylanilide diethyl phosphates was prepared as a part of our on-going search for new antimicrobial active drugs. All compounds exhibited in vitro activity against Mycobacterium tuberculosis, Mycobacterium kansasii and Mycobacterium avium strains, with minimum inhibitory concentration (MIC) values of 0.5–62.5 μmol/L. Selected salicylanilide diethyl phosphates also inhibit multidrug-resistant tuberculous strains at the concentration of 1 μmol/L. Salicylanilide diethyl phosphates also exhibited mostly the activity against Gram-positive bacteria (MICs ⩾1.95 μmol/L), whereas their antifungal activity is significantly lower. The IC50 values for Hep G2 cells were within the range of 1.56–33.82 μmol/L, but there is no direct correlation with MICs for mycobacteria. 相似文献