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1.
Three series of novel artemisinin–guanidine hybrids 4a–4f , 8a–8h and 9a–9h have been facilely synthesized via four‐component reaction (aza‐Wittig reaction) and evaluated for their anti‐tumor activities against A549, HT‐29 and MDA‐MB‐231 cell lines in vitro. All of the tested compounds showed enhanced anti‐tumor activities with IC50 values ranging from 0.02 µM to 12.0 µM as compared to DHA (dihydroartemisinin). Among them, artemisinin derived dimers, compounds 9b (IC50 = 0.05 µM), 9d (IC50 = 0.06 µM) and 9f (IC50 = 0.02 µM) were found to be most active against HT29 cells. 相似文献
2.
Xianwen Fang Bingqin Yang Zhao Cheng Meipan Yang Na Su Lizhen Zhou Jia Zhou 《Archiv der Pharmazie》2013,346(4):292-299
A series of nitrogen mustard‐linked chalcones were synthesized and evaluated for their antitumor activity in vitro against the K562 and HepG2 cell lines. The aldol condensation of [N,N‐bis(chloroethyl)‐3‐amino]‐acetophenone ( 2 ) with aromatic aldehydes afforded the nitrogen mustard‐linked chalcones. Among the analogs tested, compounds 5e and 5k exhibited significant anti‐proliferation activities against K562 cells with IC50 values of 2.55 and 0.61 µM, respectively, which revealed higher cell toxicity than the standard drugs cisplatin (IC50 > 200 µM) and adriamycin (IC50 = 14.88 µM). The methoxyl and N,N‐dimethyl groups on the B‐ring of the chalcone frame enhanced the inhibitory activities against both the K562 and HepG2 cell lines. The structure–activity relationship study indicated that the inhibitory activities significantly varied with the position(s) and species of the substituted group(s). 相似文献
3.
New 4‐arylazo‐3,5‐diamino‐1H‐pyrazole derivatives substituted in the 4‐aryl ring with the acetyl moiety were designed and synthesized. The antiproliferative activity of the novel arylazopyrazoles was examined against the MCF‐7 cell line. Among all target compounds, 8b (IC50 3.0 µM) and 8f (IC50 4.0 µM) displayed higher cytotoxicity as compared with the reference standard imatinib (IC50 7.0 µM). Further studies to explore the mechanism of action were performed on the most active hit of our library, 8b , via anti‐CDK2 kinase activity. It demonstrated good inhibitory effects for CDK2 (IC50 0.24 µM) with 62.5% inhibition, compared with imatinib. The cell cycle analysis in the MCF‐7 cell line revealed apoptosis induction by 8b and cell cycle arrest at the S phase. Docking in the CDK2 active site and pharmacophore modeling confirmed the affinity of 8b to the CDK2 active site. Absorption, distribution, metabolism, and excretion studies revealed that our target compounds are orally bioavailable, with no permeation through the blood–brain barrier. 相似文献
4.
In an attempt to develop potent and selective anti‐tumor agents, three new series of artemisinin–chalcone hybrids 10a – 10g , 11a – 11g and 12a–12h were designed, synthesized and screened for their anti‐tumor activity against five cell lines (HT‐29, A549, MDA‐MB‐231, HeLa and H460) in vitro. Among compounds 10a–g and 11a–11g , most of them displayed enhanced activity and good selectivity toward HT‐29 and HeLa cell lines with IC50 values ranging from 0.12 to 0.85 µM as compared with DHA (dihydroartemisinin). Compounds 10a and 11a are most active toward HeLa cells with IC50 values of 0.12 and 0.19 µM. The results revealed that the presence of chalcone moiety is beneficial to their activity and selectivity. In addition, compounds 12a ‐ 12h containing a ‘reversed chalcone’ moiety showed only slight improvement in activity than those of DHA. 相似文献
5.
Bo Jiang Yi Zeng Meng‐Jie Li Jin‐Yi Xu Yong‐Na Zhang Qiu‐Juan Wang Ni‐Yue Sun Tao Lu Xiao‐Ming Wu 《Archiv der Pharmazie》2010,343(9):500-508
A series of 1,5‐diaryl‐1,2,4‐triazole derivatives were synthesized and evaluated as cyclooxygenase‐2 (COX‐2) inhibitors. The results of the preliminary biological assays in vivo showed that eight compounds 5b , 6b , 6c , 7c , 8b , 8d , 9c , and 9d have potent anti‐inflammatory activity (P < 0.01), while compounds 6b , 6c , and 9c exhibit marked potency. Compound 6c was then selected for further investigation. In the COX inhibition assay in vitro, compound 6c was identified as a potent and selective inhibitor of COX‐2 (COX‐2 IC50 = 0.37 µM; SI = 0.018), being equipotent to celecoxib (COX‐2 IC50 = 0.26 µM; SI = 0.015). In a rat carrageenan‐induced paw edema assay, 6c exhibited moderate anti‐inflammatory activity (35% inhibition of inflammation) at 2 h after administration of 15 mg/kg as an oral dose. A docking study also revealed that compound 6c binds in the active site of COX‐2 in a similar mode to that of the known selective COX‐2 inhibitor SC‐558. 相似文献
6.
Turana Orujova Abdulilah Ece Gülşen Akalın Çiftçi Ahmet Özdemir Mehlika D. Altıntop 《Drug development research》2023,84(2):185-199
In an attempt to identify potent antitumor agents for the fight against non-small cell lung cancer, new thiazolyl hydrazones ( 2a–n ) were synthesized and examined for their in vitro cytotoxic effects on A549 human lung adenocarcinoma and L929 mouse embryonic fibroblast cells by means of the MTT assay. Furthermore, the effects of the most potent anticancer agents on apoptosis and Akt inhibition were investigated. 2-[2-((Isoquinolin-5-yl)methylene)hydrazinyl]−4-(4-methylsulfonylphenyl)thiazole ( 2k ) (IC50 = 1.43 ± 0.12 µM) and 2-[2-((isoquinolin-5-yl)methylene)hydrazinyl]−4-(1,3-benzodioxol-5-yl)thiazole ( 2l ) (IC50 = 1.75 ± 0.07 µM) displayed more pronounced anticancer activity than cisplatin (IC50 = 3.90 ± 0.10 µM) on A549 cell lines; 2-[2-((isoquinolin-5-yl)methylene)hydrazinyl]−4-(4-methoxyphenyl)thiazole ( 2j ) (IC50 = 3.93 ± 0.06 µM) showed anticancer activity close to cisplatin. These compounds were found to induce apoptosis in A549 cells. Compound 2j (IC50 = 3.55 ± 0.64 µM) showed stronger Akt inhibitory activity than GSK690693 (IC50 = 4.93 ± 0.06 µM), while compounds 2k and 2l did not cause Akt inhibition at IC50 concentrations (1.43 and 1.75 µM, respectively). To comprehensively elucidate the binding pose of compound 2j and to provide a detailed understanding on the ligand' binding mechanism, induced-fit docking calculations were also conducted. Both in vitro and in silico studies suggest that compound 2j shows its cytotoxic and apoptotic effects on A549 cell lines via Akt inhibition. However, it is understood that compounds 2k and 2l exert their strong anticancer effects on A549 cells through different pathways. 相似文献
7.
Anti‐inflammatory and antinociceptive effects of tilifodiolide,isolated from Salvia tiliifolia Vahl (Lamiaceae)
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《Drug development research》2018,79(4):165-172
Salvia tiliifolia Vahl (Lamiaceae) is used for the empirical treatment of pain and inflammation. The diterpenoid tilifodiolide (TFD) was isolated from Salvia tiliifolia. The in vitro anti‐inflammatory effects of TFD (0.1–200 µM) were assessed using murine macrophages stimulated with LPS and estimating the levels of pro‐inflammatory mediators for 48 h. The in vivo anti‐inflammatory activity of TFD was assessed using the carrageenan‐induced paw edema test for 6 h. The antinociceptive effects of TFD were evaluated using the formalin test and the acetic acid induced‐writhing test. The effects of TFD on locomotor activity were assessed using the open field test and the rotarod test. TFD inhibited the production of TNF‐α (IC50 = 5.66 µM) and IL‐6 (IC50 = 1.21 µM) in macrophages. TFD (200 mg/kg) showed anti‐inflammatory effects with similar activity compared to 10 mg/kg indomethacin. The administration of TFD induced antinociception in the phase 1 (ED50 = 48.2 mg/kg) and the phase 2 (ED50 = 28.9 mg/kg) of the formalin test. In the acetic acid assay, TFD showed antinociceptive effects (ED50 = 32.3 mg/kg) with similar potency compared to naproxen (ED50 = 36.2 mg/kg). In the presence of different inhibitors in the acetic acid assay, only the co‐administration of TFD and naloxone reverted the antinociceptive activity shown by TFD alone. TFD did not affect locomotor activity in mice. TFD exerts in vitro and in vivo anti‐inflammatory activity and in vivo antinociceptive effects. 相似文献
8.
Roberto Parise‐Filho Kerly Fernanda Mesquita Pasqualoto Fátima Maria Motter Magri Adilson Kleber Ferreira Bárbara Athayde Vaz Galvão da Silva Maurício Temotheo Tavares Ricardo Alexandre Azevedo Aline Vivian Vatti Auada Michelle Carneiro Polli Carlos Alberto Brandt 《Archiv der Pharmazie》2012,345(12):934-944
In this paper, the isolation of dillapiole ( 1 ) from Piper aduncum was reported as well as the semi‐synthesis of two phenylpropanoid derivatives [di‐hydrodillapiole ( 2 ), isodillapiole ( 3 )], via reduction and isomerization reactions. Also, the compounds' molecular properties (structural, electronic, hydrophobic, and steric) were calculated and investigated to establish some preliminary structure–activity relationships (SAR). Compounds were evaluated for in vitro antileishmanial activity and cytotoxic effects on fibroblast cells. Compound 1 presented inhibitory activity against Leishmania amazonensis (IC50 = 69.3 µM) and Leishmania brasiliensis (IC50 = 59.4 µM) and induced cytotoxic effects on fibroblast cells mainly in high concentrations. Compounds 2 (IC50 = 99.9 µM for L. amazonensis and IC50 = 90.5 µM for L. braziliensis) and 3 (IC50 = 122.9 µM for L. amazonensis and IC50 = 109.8 µM for L. brasiliensis) were less active than dillapiole ( 1 ). Regarding the molecular properties, the conformational arrangement of the side chain, electronic features, and the hydrophilic/hydrophobic balance seem to be relevant for explaining the antileishmanial activity of dillapiole and its analogues. 相似文献
9.
Design,synthesis, and molecular docking study of 3H‐imidazole[4,5‐c]pyridine derivatives as CDK2 inhibitors
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Yi‐Zhe Wu Hua‐Zhou Ying Lei Xu Gang Cheng Jing Chen Yong‐Zhou Hu Tao Liu Xiao‐Wu Dong 《Archiv der Pharmazie》2018,351(6)
10.
Abdel‐Ghany A. El‐Helby Helmy Sakr Ibrahim H. Eissa Hamada Abulkhair Ahmed A. Al‐Karmalawy Khaled El‐Adl 《Archiv der Pharmazie》2019,352(10)
Novel series of benzoxazole s 4 a‐f ‐16 were designed, synthesized, and evaluated for anticancer activity against HepG2, HCT‐116, and MCF‐7 cells. HCT‐116 was the most sensitive cell line to the influence of the new derivatives. In particular, compound 5 e was found to be the most potent against HepG2, HCT‐116, and MCF‐7 with IC50 = 4.13 ± 0.2, 6.93 ± 0.3, and 8.67 ± 0.5 µM, respectively. Compounds 5 c , 5 f , 6 b , 5 d , and 6 c showed the highest anticancer activities against HepG2 cells with IC50 of 5.93 ± 0.2, 6.58 ± 0.4, 8.10 ± 0.7, 8.75 ± 0.7, and 9.95 ± 0.9 µM, respectively; HCT‐116 cells with IC50 of 7.14 ± 0.4, 9.10 ± 0.8, 7.91 ± 0.6, 9.52 ± 0.5, and 12.48 ± 1.1 µM, respectively; and MCF‐7 cells with IC50 of 8.93 ± 0.6, 10.11 ± 0.9, 12.31 ± 1.0, 9.95 ± 0.8, and 15.70 ± 1.4 µM, respectively, compared with sorafenib as a reference drug with IC50 of 9.18 ± 0.6, 5.47 ± 0.3, and 7.26 ± 0.3 µM, respectively. The most active compounds 5 c‐f and 6 b,c were further evaluated for their vascular endothelial growth factor receptor‐2 (VEGFR‐2) inhibition. Compounds 5 e and 5 c potently inhibited VEGFR‐2 at lower IC50 values of 0.07 ± 0.01 and 0.08 ± 0.01 µM, respectively, compared with sorafenib (IC50 = 0.1 ± 0.02 µM). Compound 5 f potently inhibited VEGFR‐2 at low IC50 value (0.10 ± 0.02 µM) equipotent to sorafenib. Our design was based on the essential pharmacophoric features of the VEGFR‐2 inhibitor sorafenib. Molecular docking was performed for all compounds to assess their binding pattern and affinity toward the VEGFR‐2 active site. 相似文献
11.
Methylenebisphosponic acid tetraethyl ester ( 1 ) was added to 2‐azido‐ 7a–e and 2‐chloroquinoline‐3‐chalcones 10a–e in boiling sodium ethanolate solution to give, via Michael addition, tetrazolo[1,5‐a]quinoline‐ 8a–d , 13a and 2‐chloroquinoline‐based bisphosphonates 11a–d , 14a in E‐configuration. Further acid hydrolysis afforded the respective BP‐acid analogues E‐ 9a–d , 12a–d , 13b , and 14b in excellent yields. Anti‐tumor activity screening for the new BP‐acids at a dose of 10 µM utilizing 44 different human tumor cell lines representing breast, ovary, prostate, lung, and CNS cancer as well as leukemia and melanoma was carried out. Eight of ten tested compounds exhibited remarkable anti‐tumor activity against breast and prostate cancer, and a promising anti‐tumor sensitivity toward ovarian cancer and melanoma. Conversely, there was only scattered activity against leukemia and no noticeable action of these BP‐acids on CNS or lung cancer. Based on the prediction results (PASS program), anti‐inflammatory activity of the new acids was also determined in vivo, by the acute carrageenin induced paw edema in rats. Many of these compounds showed anti‐inflammatory properties at a dose of 50 mg/kg body weight. 相似文献
12.
Khaled El-Adl Mohamed K. Ibrahim Fathalla Khedr Hamada S. Abulkhair Ibrahim H. Eissa 《Archiv der Pharmazie》2022,355(1):2100278
Twenty new N-substituted-4-phenylphthalazin-1-amine derivatives were designed, synthesized, and evaluated for their anticancer activities against HepG2, HCT-116, and MCF-7 cells as VEGFR-2 inhibitors. HCT-116 was the most sensitive cell line to the influence of the new derivatives. In particular, compound 7f was found to be the most potent derivative among all the tested compounds against the three cancer cell lines, with 50% inhibition concentration, IC50 = 3.97, 4.83, and 4.58 µM, respectively, which is more potent than both sorafenib (IC50 = 9.18, 5.47, and 7.26 µM, respectively) and doxorubicin (IC50 = 7.94, 8.07, and 6.75 µM, respectively). Fifteen of the synthesized derivatives were selected to evaluate their inhibitory activities against VEGFR-2. Compound 7f was found to be the most potent derivative that inhibited VEGFR-2 at an IC50 value of 0.08 µM, which is more potent than sorafenib (IC50 = 0.10 µM). Compound 8c inhibited VEGFR-2 at an IC50 value of 0.10 µM, which is equipotent to sorafenib. Moreover, compound 7a showed very good activity with IC50 values of 0.11 µM, which is nearly equipotent to sorafenib. In addition, compounds 7d , 7c , and 7g possessed very good VEGFR-2-inhibitory activity, with IC50 values of 0.14, 0.17, and 0.23 µM, respectively. 相似文献
13.
Design,synthesis, and biological evaluation of novel 1,2‐diaryl‐4‐substituted‐benzylidene‐5(4H)‐imidazolone derivatives as cytotoxic agents and COX‐2/LOX inhibitors
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14.
《Pharmaceutical biology》2013,51(6):716-721
Phytochemical investigations on the ethyl acetate soluble fraction of the whole plant of Isatis costata Linn. (Brassicaseae) led to the isolation of the oxindole alkaloids costinones A (1), B (2), isatinones A (3), B (4), indirubin (5), and trisindoline (6). Compounds 1–6 displayed significant to moderate inhibition against xanthine oxidase enzyme with IC50 values ranging from 90.3?±?0.06 to 179.6?±?0.04 µM, whereas the standard inhibitor of xanthine oxidase (allopurinol) had an IC50 value of 7.4?±?0.07 µM. Compounds 1 (IC50 7.21?±?0.05 µM), 2 (IC50 9.40?±?0.03 µM), 3 (IC50 11.51?±?0.07 µM), 4 (IC50 12.53?±?0.06 µM), 5 (IC50 14.29?±?0.09 µM), and 6 (IC50 17.34?±?0.04 µM) exhibited pronounced activities when compared with the standard tyrosinase inhibitor l-mimosine (IC50 3.70?±?0.03 µM), along with DPPH radical scavenging activity with IC50 226, 270, 300, 320, 401, and 431 µM, respectively. The crude extract and compounds 1, 2, 5, and 6 showed significant antifungal activity against Trichophyton schoen leinii, Aspergillus niger, Candida albicans, Trichophyton simii, and Macrophomina phaseolina. 相似文献
15.
Kristyna Krasulova Michal Siller Ondrej Holas Zdenek Dvorak 《Xenobiotica; the fate of foreign compounds in biological systems》2016,46(4):315-324
1.?The aim of this work was to examine the differences in the inhibitory potency of individual enantiomers and racemic mixtures of selected chiral drugs on human liver microsomal cytochromes P450.2.?The interaction of enantiomeric forms of six drugs (tamsulosin, tolterodine, citalopram, modafinil, zopiclone, ketoconazole) with nine cytochromes P450 (CYP3A4, CYP2E1, CYP2D6, CYP2C19, CYP2C9, CYP2C8, CYP2B6, CYP2A6, CYP1A2) was examined. HPLC methods were used to estimate the extent of the inhibition of specific activity in vitro.3.?Tamsulosin (TAM) and tolterodine (TOL) inhibited CYP3A4 activity with an enantiospecific pattern. The inhibition of CYP3A4 activity differed for R-TAM (Ki 2.88?±?0.12?µM) and S-TAM (Ki 14.22?±?0.53?µM) as well as for S-TOL (Ki 1.71?±?0.03?µM) and R-TOL (Ki 4.78?±?0.17?µM). Also, the inhibition of CYP2C19 by ketoconazole (KET) cis-enantiomers exhibited enantioselective behavior: the (+)-KET (IC50 23.64?±?6.25?µM) was more potent than (?)-KET (IC50 66.12?±?12.6?µM). The inhibition of CYP2C19 by modafinil (MOD) enantiomers (R-MOD IC50?=?51.79?±?8.58?µM, S-MOD IC50?=?48.62?±?9.74?µM) and the inhibition of CYP2D6 by citalopram (CIT) enantiomers (R-CIT IC50?=?68.17?±?5.70?µM, S-CIT IC50?=?62.63?±?7.89?µM) was not enantiospecific.4.?Although enantiospecific interactions were found (TAM, TOL, KET), they are probably not clinically relevant as the plasma levels are generally lower than the drug concentration needed for prominent inhibition (at least 50% of CYP activity). 相似文献
16.
Novel series of pyrazole derivatives were synthesized and tested for their in vivo anti‐malarial activity using mice infected with chloroquine sensitive P. berghei at a dose level of 50 µmol/kg. The most active compounds were further tested in vitro against chloroquine resistant (RKL9) strain of P. falciparum. The in vivo anti‐malarial activity study indicated that compounds 2a, 2b, 8a and 8b had mean percent suppression of 85%, 83%, 95% and 97%, respectively at equimolar dose level of the standard drug chloroquine diphosphate. Moreover, compounds 2a, 2b, 8a and 8b showed in vitro IC50 values lower (p < 0.05) than that of the standard drug chloroquine phosphate (0.188 ± 0.003 µM) using the RKL9 strain. Compound 8b was the most active with IC50 of 0.033 ± 0.014 µM. Generally, among the tested compounds, those containing a free carboxylic acid functional group on the pyrazole ring were the most active and this finding was supported by the docking results performed for the active compounds. The acute toxicity studies of the active compounds revealed that they have a good safety profile. 相似文献
17.
Eman E. Nasr Amany S. Mostafa Magda A. A. El‐Sayed Mohammed A. M. Massoud 《Archiv der Pharmazie》2019,352(7)
New quinolines substituted with various heterocycles and chalcone moieties were synthesized and evaluated as antitumor agents. All the synthesized compounds were in vitro screened against 60 human cancer cell lines. Compound 13 showed the highest cytotoxicity toward 58 cell lines, exhibiting distinct growth inhibition values (GI50) against the majority of them, including SR, HL‐60 (TB) strains (leukemia), and MDA‐MB‐435 strains (melanoma), with GI50 values of 0.232, 0.260, and 0.300 µM, respectively. It exhibited great selectivity toward cancer cell lines, with less toxic effect against normal cells represented by skin fibroblast (BJ) and breast epithelial cell lines (MCF‐10F). The enzyme inhibitory activity of compound 13 was evaluated against topoisomerase 1 (Topo 1), epidermal growth factor receptor and vascular endothelial growth factor receptor 2, where it displayed worthy Topo 1 inhibition activity with an IC50 value of 0.278 µM compared with camptothecin as a reference drug (IC50 0.224 µM). Docking studies were performed to investigate the recognition profile of compound 13 with the Topo 1 enzyme binding site. 相似文献
18.
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
19.
Zhen Xiao Fei Lei Xiuying Chen Xiaolei Wang Lujie Cao Kejun Ye Wufu Zhu Shan Xu 《Archiv der Pharmazie》2018,351(6)
20.
A new series of 1,4‐disubstituted phthalazinylpiperazine derivatives 7a–f , 12a–f and 20a–f were designed and synthesized in order to develop potent and selective antitumor agents. The target compounds were screened for their cytotoxic activities against A549, HT‐29 and MDA‐MB‐231 cancer cell lines in vitro. Among them, compounds 7a–f exhibited excellent selectivity for MDA‐MB‐231 with IC50 values ranging from 0.013 µM to 0.079 µM. The most promising compound, 7e (IC50 = 2.19 µM, 2.19 µM, 0.013 µM), was 9.3, 10, and 4.9 × 103 times more active than vatalanib (IC50 = 20.27 µM, 21.96 µM, 63.90 µM), respectively. 相似文献