共查询到20条相似文献,搜索用时 15 毫秒
1.
Rangappa S. Keri Sudam S. Pandule Srinivasa Budagumpi Bhari M. Nagaraja 《Archiv der Pharmazie》2018,351(5)
2.
Oriana Tabarrini Stefano Sabatini Serena Massari Marco Pieroni Scott G. Franzblau Violetta Cecchetti 《Chemical biology & drug design》2012,80(5):781-786
The screening of an in‐house quinolones library against Mycobacterium tuberculosis (Mtb) H37Rv, followed by a first cycle of optimization, yielded 6‐hydrogen‐8‐methyl derivatives endowed with good potency. The antitubercular activity also encompassed the bacteria in a non‐replicating state (NRP‐TB) with minimum inhibitory concentration values lower than those of the reference agent, moxifloxacin. Among the best compounds, 11w and 11ai , characterized by a properly substituted piperidine at the C‐7 position, were active against single‐drug‐resistant (SDR‐TB) Mtb strains, maintaining overall good potency also against ciprofloxacin‐resistant Mtb. This study expands the body of SAR around antitubercular quinolones leading to reconsider the role played by the usual fluorine atom at the C‐6 position. Further elaboration of the 6‐hydrogen‐8‐methylquinolone scaffold, with a particular focus on the C‐7 position, is expected to give even more potent congeners holding promise for shortening the current anti‐TB regimen. 相似文献
3.
Synthesis,biological evaluation,and docking studies of some 5‐chloro‐2(3H)‐benzoxazolone Mannich bases derivatives as cholinesterase inhibitors 下载免费PDF全文
Sirin Uysal Sulunay Parlar Ayse H. Tarikogullari Fadime Aydin Kose Vildan Alptuzun Zeynep Soyer 《Archiv der Pharmazie》2018,351(3-4)
4.
Shasank S. Swain Sudhir K. Paidesetty Rabindra N. Padhy Tahziba Hussain 《Chemical biology & drug design》2020,96(2):714-730
Mycobacterium tuberculosis (Mtb) causes one of the most grievous pandemic infectious diseases, tuberculosis (TB), with long‐term morbidity and high mortality. The emergence of drug‐resistant Mtb strains, and the co‐infection with human immunodeficiency virus, challenges the current WHO‐TB stewardship programs. The first‐line anti‐TB drugs, isoniazid (INH) and rifampicin (RIF), have become extensively obsolete in TB control from chromosomal mutations during the last decades. However, based on clinical trial statistics, the production of well‐tolerated anti‐TB drug(s) is miserably low. Alternately, semi‐synthesis or structural modifications of first‐line obsolete antitubercular drugs remain as the versatile approach for getting some potential medicines. The use of any suitable phytochemicals with INH in a hybrid formulation could be an ideal approach for the development of potent anti‐TB drug(s). The primary objective of this review was to highlight and analyze available INH–phytochemical hybrid research works. The utilization of phytochemicals through chemical conjugation is a new trend toward the development of safer/non‐toxic anti‐TB drugs. 相似文献
5.
Synthesis,molecular docking,and pharmacological evaluation of N‐(2‐(3,5‐dimethoxyphenyl)benzoxazole‐5‐yl)benzamide derivatives as selective COX‐2 inhibitors and anti‐inflammatory agents 下载免费PDF全文
6.
Imen Boualia Chamseddine Derabli Raouf Boulcina Chawki Bensouici Muhammet Yildirim Arzu Birinci Yildirim El Hassen Mokrani Abdelmadjid Debache 《Archiv der Pharmazie》2019,352(11)
A series of bis(4‐amino‐5‐cyano‐pyrimidines) was synthesized and evaluated as dual inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). To further explore the multifunctional properties of the new derivatives, their antioxidant and antibacterial activities were also tested. The results showed that most of these compounds could effectively inhibit AChE and BChE. Particularly, compound 7c exhibited the best AChE inhibitory activity (IC50 = 5.72 ± 1.53 μM), whereas compound 7h was identified as the most potent BChE inhibitor (IC50 = 12.19 ± 0.57 μM). Molecular modeling study revealed that compounds 7c, 7f , and 7b showed a higher inhibitory activity than that of galantamine against both AChE and BChE. Anticholinesterase activity of compounds 7h, 7b , and 7c was significant in vitro and in silico for both enzymes, since these compounds have hydrophobic rings (Br‐phenyl, dimethyl, and methoxyphenyl), which bind very well in both sites. In addition to cholinesterase inhibitory activities, these compounds showed different levels of antioxidant activities. Indeed, in the superoxide–dimethyl sulfoxide alkaline assay, compound 7j showed very high inhibition (IC50 = 0.37 ± 0.28 μM). Also, compound 7l exhibited strong and good antibacterial activity against Staphylococcus epidermidis and Staphylococcus aureus, respectively. Taking into account the results of biological evaluation, further modifications will be designed to increase potency on different targets. In this study, the obtained results can be a new starting point for further development of multifunctional agents for the treatment of Alzheimer's disease. 相似文献
7.
Wei Jia Yanfang Zhao Rongdong Li Yanjiao Wu Zebiao Li Ping Gong 《Archiv der Pharmazie》2009,342(9):507-512
A series of 9‐methoxy‐6H‐[1]benzothiopyrano[4,3‐b]quinolin‐10‐ols with a Mannich side chain were synthesized and evaluated for their anti‐Hepatitis B virus (HBV) activity in HepG2.2.15 cells. Some compounds showed significant anti‐HBV activity with IC50 values less than 41 μM. Among them, compound 9b was the most effective anti‐HBV agent (IC50 = 1.7 μM, SI = 60.3). 相似文献
8.
Synthesis,p38α MAP kinase inhibition,anti‐inflammatory activity,and molecular docking studies of 1,2,4‐triazole‐based benzothiazole‐2‐amines 下载免费PDF全文
9.
Screening of non‐steroidal anti‐inflammatory drugs for inhibitory effects on the activities of six UDP‐glucuronosyltransferases (UGT1A1, 1A3, 1A4, 1A6, 1A9 and 2B7) using LC‐MS/MS 下载免费PDF全文
Jeongmin Joo Yang‐Weon Kim Zhexue Wu Jung‐Hoon Shin Boram Lee Jong Cheol Shon Eun Young Lee Nguyen Minh Phuc Kwang‐Hyeon Liu 《Biopharmaceutics & drug disposition》2015,36(4):258-264
Non‐steroidal anti‐inflammatory drugs (NSAIDs) are used widely to relieve pain and to decrease inflammation. Several clinical studies have reported that NSAIDs inhibit uridine 5′‐diphospho‐glucuronosyltransferase (UGT) enzymes. Therefore, the study evaluated the inhibitory potential of 15 NSAIDs on the activities of six UGT isoforms (i.e. UGT1A1, 1A3, 1A4, 1A6, 1A9 and 2B7) in human liver microsomes (HLMs). Among the 15 NSAIDs tested here, mefenamic acid and diclofenac inhibited all UGTs tested in this study. Piroxicam and niflumic acid inhibited UGT1A9 activity (IC50 = 73.8 μm and 0.38 μm , respectively) and naproxen selectively inhibited UGT2B7 activity (IC50 = 53.1 μm ), whereas it did not inhibit the other UGTs tested (IC50 > 200 μm ). Diflunisal inhibited the UGT1A1 (IC50 = 33.0 μm ) and UGT1A9 (IC50 = 19.4 μm ). Acetaminophen, fenoprofen, ibuprofen, ketoprofen, meloxicam, phenylbutazone, salicylic acid and sulindac showed negligible inhibitory effects on the six UGTs (IC50 > 100 μm ). These results suggest that some NSAIDs have the potential to inhibit UGTs in vitro. Copyright © 2014 John Wiley & Sons, Ltd. 相似文献
10.
Ji Yu Haiyong Jia Xiaowei Guo Samuel Desta Shuo Zhang Jian Zhang Xiao Ding Xiaohong Liang Xinyong Liu Peng Zhan 《Chemical biology & drug design》2020,95(6):567-583
In continuation of our efforts toward the discovery of potent non‐nucleoside hepatitis B virus (HBV) inhibitors with novel structures, we have explored the solvent‐exposed protein region of heteroaryldihydropyrimidine derivatives. Herein, the morpholine ring of GLS4 was replaced with substituted sulfonamides and triazoles to generate novel non‐nucleoside HBV inhibitors with desirable potency. In in vitro biological evaluation, several derivatives showed good anti‐HBV DNA replication activity compared to lamivudine. In particular, compound II‐1 displayed the most potent activity against HBV DNA replication (IC50 = 0.35 ± 0.04 μM). The preliminary structure–activity relationships of the new compounds were summarized, which may help in discovering more potent anti‐HBV agents via rational drug design. 相似文献
11.
Jian‐Jun Xi Ruo‐Yu He Jian‐Kang Zhang Zhao‐Bin Cai Rang‐Xiao Zhuang Yan‐Mei Zhao Yi‐Dan Shao Xu‐Wang Pan Ting‐Ting Shi Zuo‐Jun Dong Shou‐Rong Liu Li‐Min Kong 《Archiv der Pharmazie》2019,352(8)
A series of novel 3‐(thiophen‐2‐ylthio)pyridine derivatives as insulin‐like growth factor 1 receptor (IGF‐1R) inhibitors was designed and synthesized. IGF‐1R kinase inhibitory activities and cytotoxicities against HepG2 and WSU‐DLCL2 cell lines were tested. For all of these compounds, potent cancer cell proliferation inhibitory activities were observed, but not through the inhibition of IGR‐1R. Selected compounds were further screened against various kinases. Typical compound 22 (50% inhibitory concentration [IC50] values, HepG2: 2.98 ± 1.11 μM and WSU‐DLCL2: 4.34 ± 0.84 μM) exhibited good inhibitory activities against fibroblast growth factor receptor‐2 (FGFR2), FGFR3, epidermal growth factor receptor, Janus kinase, and RON (receptor originated from Nantes), with IC50 values ranging from 2.14 to 12.20 μM. Additionally, the cell‐cycle analysis showed that compound 22 could arrest HepG2 cells in the G1/G0 phase. Taken together, all the experiments confirmed that the compounds in this series were multitarget anticancer agents worth further optimizing. 相似文献
12.
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
13.
Design,synthesis, and biological evaluation of novel 5‐Alkyl‐6‐Adamantylmethylpyrimidin‐4(3H)‐ones as HIV‐1 non‐nucleoside reverse‐transcriptase inhibitors 下载免费PDF全文
Wenxin Li Boshi Huang Dongwei Kang Erik De Clercq Dirk Daelemans Christophe Pannecouque Peng Zhan Xinyong Liu 《Chemical biology & drug design》2016,88(3):380-385
14.
Esra Tatar İlkay Küçükgüzel Dirk Daelemans Tanaji T. Talele Neerja Kaushik‐Basu Erik De Clercq Christophe Pannecouque 《Archiv der Pharmazie》2013,346(2):140-153
In accordance with our antiviral drug development attempt, acylhydrazone derivatives bearing amino acid side chains were synthesized for the evaluation of their antiviral activity against various types of viruses. Among these compounds, 8 S , 11 S , and 12 S showed anti‐HIV‐1 activity with a 50% inhibitory concentration (IC50) = 123.8 µM (selectivity index, SI > 3), IC50 = 12.1 µM (SI > 29), IC50 = 17.4 µM (SI > 19), respectively. Enantiomers 8 R , 11 R , and 12 R were inactive against the HIV‐1 strain IIIB. Hydrazones 8 S , 11 S , and 12 S which were active against HIV‐1 wild type showed no inhibition against a double mutant NNRTI‐resistant strain (K103N;Y181C). Molecular docking calculations of R‐ and S‐enantiomers of 8 , 11 , and 12 were performed using the hydrazone‐bound novel site of HIV‐1 RT. 相似文献
15.
Sammy Agudoawu Huiying Li Amgad G. Habeeb P.N. Praveen Rao Mavanur R. Suresh Edward E. Knaus 《Drug development research》2000,49(2):75-84
A group of methyl 2‐methyl‐2‐[2‐(4‐benzoyl‐5‐phenyl‐7‐halo‐2‐azabicyclo[4.1.0]hept‐3‐ene)]acetates ( 10–15 ), and the related acetamide derivative ( 16 ), that possess a variety of C‐7 substituents (Br, Cl, F, H), were designed for evaluation as analgesic‐antiinflammatory agents. The effect of the C‐7 substituent(s) and the nature of the acetic acid ester (R1 = Ome) or acetamide (R1 = NH2) moiety on analgesic activity was determined using a 4% NaCl‐induced abdominal constriction assay. Compounds 10–16 inhibited writhing by 36–82%, relative to the reference drugs aspirin (58% inhibition) and celecoxib (62% inhibition). The nature of the C‐7 substituents was a determinant of analgesic activity in the 7,7‐dihalo group of compounds where the relative activity profile was 7‐Cl2 > 7‐Br2 > 7‐F2 > 7‐Cl,7‐F, and for 7‐monohalo compounds where the potency order was 7‐Br > 7‐Cl. Elaboration of the 7,7‐dibromo methyl acetate ester ( 10 ) to the corresponding acetamide derivative ( 16 ) enhanced analgesic activity. The nature of the 7‐halo substituent(s) in the 7,7‐dihalo group of compounds was a determinant of antiinflammatory activity, determined using the carrageenan‐induced rat paw edema assay, where the relative potency order was 7‐Br2 > 7‐Cl2 > 7‐F2 > 7‐Cl,7‐F. The most potent 7,7‐dibromo compound ( 10 ) inhibited inflammation by 62%, relative to the reference drug ibuprofen (44%), and 10 inhibited COX‐2 (IC50 = 26.4 μM) and COX‐1 (IC50 = 227 μM) for a COX‐2 selectivity index of 8.6. Docking 10 in the active site of human COX‐2 showed it binds in the center of the COX‐2 binding site with the C‐5 phenyl ring oriented toward the acetylation site (Ser530), and the phenyl group of the C‐4 benzoyl moiety oriented in the vicinity of the COX‐2 secondary binding pocket near Val523. Drug Dev. Res. 49:75–84, 2000. © 2000 Wiley‐Liss, Inc. 相似文献
16.
Design,Synthesis, and Biological Evaluation of Novel 4‐Aminopiperidinyl‐linked 3,5‐Disubstituted‐1,2,6‐thiadiazine‐1,1‐dione Derivatives as HIV‐1 NNRTIs 下载免费PDF全文
Tao Liu Boshi Huang Ye Tian Xin Liang Hong Liu Huiqing Liu Peng Zhan Erik De Clercq Christophe Pannecouque Xinyong Liu 《Chemical biology & drug design》2015,86(1):107-113
Based on the hybridization of the privileged fragments in DABO and DAPY‐typed HIV‐1 NNRTIs, a novel series of 4‐aminopiperidinyl‐linked 3,5‐disubstituted‐1,2,6‐thiadiazine‐1,1‐dione derivatives were designed, synthesized, and evaluated for their in vitro anti‐HIV activities in MT‐4 cells. Most of the target compounds showed weak inhibitory activity against WT HIV‐1. In order to confirm the mode of action of the target compounds, representative compounds Ba8 and Bb8 were selected to perform the HIV‐1 RT inhibitory assay. In this assay, Ba8 and Bb8 displayed good activity with IC50 values of 3.15 and 1.52 μm , respectively. Additionally, preliminary structure–activity relationships (SARs) analysis and molecular docking studies of newly synthesized compounds are also discussed. 相似文献
17.
Novel pyridine‐2,4,6‐tricarbohydrazide thiourea compounds as small key organic molecules for the potential treatment of type‐2 diabetes mellitus: In vitro studies against yeast α‐ and β‐glucosidase and in silico molecular modeling 下载免费PDF全文
Tanzeel Ur. Rehman Sadaf Riaz Islam Ullah Khan Muhammad Ashraf Marek Bajda Alicja Gawalska Muhammad Yar 《Archiv der Pharmazie》2018,351(1)
A range of novel pyridine‐2,4,6‐tricarbohydrazide thiourea compounds ( 4a–i ) were synthesized in good to excellent yields (63–92%). The enzyme inhibitory potentials of these compounds were investigated against α‐ and β‐glucosidases because these enzymes play a crucial role in treating type‐2 diabetes mellitus (T2DM). As compared to the reference compound acarbose (IC50 38.22 ± 0.12 μM), compounds 4i (IC50 25.49 ± 0.67 μM), 4f (IC50 28.91 ± 0.43 μM), 4h (IC50 30.66 ± 0.52 μM), and 4e (IC50 35.01 ± 0.45 μM) delivered better inhibition against α‐glucosidase and were quite inactive/completely inactive against β‐glucosidase. The structure–activity relationship of these compounds was developed and elaborated with the help of molecular docking studies. 相似文献
18.
In silico approaches and chemical space of anti‐P‐type ATPase compounds for discovering new antituberculous drugs 下载免费PDF全文
Tuberculosis (TB) is one of the most important public health problems around the world. The emergence of multi‐drug‐resistant (MDR) and extensively drug‐resistant (XDR) Mycobacterium tuberculosis strains has driven the finding of alternative anti‐TB targets. In this context, P‐type ATPases are interesting therapeutic targets due to their key role in ion homeostasis across the plasma membrane and the mycobacterial survival inside macrophages. In this review, in silico and experimental strategies used for the rational design of new anti‐TB drugs are presented; in addition, the chemical space distribution based on the structure and molecular properties of compounds with anti‐TB and anti‐P‐type ATPase activity is discussed. The chemical space distribution compared to public compound libraries demonstrates that natural product libraries are a source of novel chemical scaffolds with potential anti‐P‐type ATPase activity. Furthermore, compounds that experimentally display anti‐P‐type ATPase activity belong to a chemical space of molecular properties comparable to that occupied by those approved for oral use, suggesting that these kinds of molecules have a good pharmacokinetic profile (drug‐like) for evaluation as potential anti‐TB drugs. 相似文献
19.
Dale O. Kiesewetter Kathleen Knudson Matt Collins Sharat Srinivasula Esther Lim Michele Di Mascio 《Journal of labelled compounds & radiopharmaceuticals》2008,51(4):187-194
Therapy for human immunodeficiency virus (HIV)‐infected patients requires chronic multidrug administration. The eventual failure of therapy in some patients has brought into question the tissue concentration of the drugs. With an appropriately radiolabeled compound, we could utilize positron emission tomography to provide quantitative time–activity curves for various tissues. We have developed a fluorine‐18 labeled analog of Tenofovir, the active metabolite of Tenofovir DF, a commonly prescribed component of multidrug therapy. Because (1‐(6‐amino‐9H‐purin‐9‐yl)‐3‐fluoropropan‐2‐yloxy)methylphosphonic acid (FPMPA) has a chiral center, we prepared both enantiomers and confirmed that the S‐isomer exhibited significantly higher antiviral activity than the R‐isomer. In viral replication inhibition assays in human MT4 cells infected with SHIVDH12R , S‐FPMPA had an IC50 of 1.85 µM (95% CI; 0.8–5.53), while the R‐isomer was inactive. An appropriate chiral precursor was prepared to allow the incorporation of fluorine‐18. The [18F]FPMPA in racemic, R, or S form was prepared in a 50 min synthesis in 38±5% yield (n=23, corrected for decay). The product was of high radiochemical and enantiomeric purity. The specific activity of the final product was 4.0±1.8 Ci/µmol at EOB (end of bombardment). This product may provide information about drug tissue distribution in animal models under chronic drug treatment. Copyright © 2008 John Wiley & Sons, Ltd. 相似文献