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1.
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
2.
A novel series of indolin‐2‐one derivatives containing the 4‐thiazolidinone moiety ( 5a—5p ) was synthesized and the cytotoxicity of these derivatives was evaluated in vitro against three human cancer cell lines (HT‐29, H460 and MDA‐MB‐231) by standard MTT assay. Some prepared compounds exhibited significant cytotoxicity against different human cancer cell lines. Several potent compounds were further evaluated against one normal cell line (WI‐38). In particular, the promising compound 5h showed remarkable cytotoxicity and selectivity against the HT‐29 and H460 cancer cell lines (IC50 = 0.016 µmol/L, 0.0037 µmol/L, respectively). 相似文献
3.
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
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.
Wufu Zhu Yajing Liu Yanfang Zhao Haiyan Wang Li Tan Weijie Fan Ping Gong 《Archiv der Pharmazie》2012,345(10):812-821
A series of 6‐hydrazinyl‐2,4‐bismorpholino pyrimidine and 1,3,5‐triazine derivatives ( 5a – 5l and 8a – 8o ) were synthesized and their chemical structures as well as the relative stereochemistry were confirmed. All the synthesized compounds were evaluated for antiproliferative activity against three cancer cell lines (H460, HT‐29, and MDA‐MB‐231). Several potent compounds were further evaluated against two other cell lines (U87MG, H1975). Most of the prepared compounds, particularly compounds 5c and 5j with IC50 values (0.07 and 0.05 µM, respectively) in the nM range, exhibited moderate to excellent antiproliferative activity and high selectivity against the H460 cancer cell line as compared with compound 1 . The most promising compound 5j , possessing a cyano group at the 3‐position of the benzene ring, showed strong antiproliferative activity against H460, HT‐29, and MDA‐MB‐231 cell lines with IC50 values of 0.05, 6.31, and 6.50 µM, which were 4.6‐ to 190.4‐fold more active than compound 1 (9.52, 29.24, and 36.21 µM), respectively. 相似文献
6.
A new series of 2,5‐diaryliminothiazolidin‐4‐ones were designed and synthesized as potent antiproliferative agents. The antiproliferative activities of the 25 target compounds were evaluated against three cancer cell lines (A549, H460 and HT29) by MTT assay. Pharmacological data indicated that most of the compounds possessed moderate activity, some showed remarkable activity against one or more cell lines. As the most promising compound, 8s (with IC50 values of 1.1, 0.01 and 1.3 µM against the A549, H460 and HT29 cell lines) was 1.1‐ to 270‐fold more potent than the reference drug sorafenib. Furthermore, preliminary structure–activity relationships (SARs) were summarized to provide guidance for further design and discovery of 2‐iminothiazolidin‐4‐one‐based antiproliferative agents. 相似文献
7.
Design,Synthesis and Molecular Docking Studies of Novel Indole–Pyrimidine Hybrids as Tubulin Polymerization Inhibitors
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Meng‐Jin Hu Bei Zhang Hai‐Kui Yang Yang Liu Yu‐Rong Chen Tian‐Zhu Ma Ling Lu Wen‐Wei You Pei‐Liang Zhao 《Chemical biology & drug design》2015,86(6):1491-1500
A series of novel hybrids of indole–pyrimidine‐containing piperazine moiety were designed, synthesized and evaluated for their antiproliferative and tubulin polymerization inhibitory activities. The results indicated that most of these compounds possessed significant cytotoxic potency against four cancer cell lines, HT‐29, A549, MDA‐MB‐231 and MCF‐7. Particularly, the most promising compound 34 showed more potent and broad‐spectrum cytotoxic activities with the IC50 values ranged from 5.01 to 14.36 μm against A549, MDA‐MB‐231 and MCF‐7 cell lines. Meanwhile, 34 also displayed the most potent tubulin polymerization inhibitory activity with IC50 value of 11.2 μm . Furthermore, molecular docking analysis demonstrated 34 interacts and binds efficiently with the tubulin protein at the colchicine‐binding site. It was worth noting that the compound did not affect the normal human embryonic kidney cells, HEK‐293. These results suggest that this novel class of indole–pyrimidine hybrids may have potential to be developed as new a class of tubulin polymerization inhibitors. 相似文献
8.
Liu W Zhou J Qi F Bensdorf K Li Z Zhang H Qian H Huang W Cai X Cao P Wellner A Gust R 《Archiv der Pharmazie》2011,344(7):451-458
In an attempt to develop potent and selective anti‐tumor drugs, a series of novel 2‐amino‐thiazole‐5‐carboxylic acid phenylamide derivatives were designed based on the structure of dasatinib. All compounds were synthesized by a systematic combinatorial chemical approach. Biological evaluation revealed that N‐(2‐chloro‐6‐methylphenyl)‐2‐(2‐(4‐methylpiperazin‐1‐yl)acetamido)thiazole‐5‐carboxamide ( 6d ) exhibited high antiproliferative potency on human K563 leukemia cells comparable to dasatinib. Against mammary and colon carcinoma cells 6d was either inactive (MDA‐MB 231) or distinctly less active (MCF‐7 and HT‐29: IC50 = 20.2 and 21.6 µM, respectively). Dasatinib showed at each cell line IC50 < 1 µM. The results of this structure activity relationship study clearly documented that the pyrimidin‐4‐ylamino core of dasatinib is responsible for the anti‐tumor activity against non‐leukemia cell lines. 相似文献
9.
Kamel Metwally Ashraf Khalil Harris Pratsinis Dimitris Kletsas 《Archiv der Pharmazie》2010,343(8):465-472
As part of our ongoing research effort to develop new antimitotic agents based on the recently reported pyrimido[4,5‐c]quinoline‐1(2H)‐one ring skeleton, we were interested in identifying structural elements that contribute to the cytotoxicity of this class of compounds. The effect of several quinoline‐ring substituents was examined and the new compounds were evaluated in vitro for cytotoxicity against three human cancer cell lines namely, lung fibrosarcoma HT‐1080, colon adenocarcinoma HT‐29, and breast carcinoma MDA‐MB‐231. Most of the compounds showed cytotoxic activity in the low micromolar and sub‐micromolar range. Structure‐activity relationship information revealed that a combination of electronic and steric factors may be involved. Flow cytometric cell cycle analysis performed on HT‐1080 cells revealed that the most cytotoxic compounds 48 , 50 , 54 , 59 , and 63 inhibit the S‐phase and arrest the cells in the G2/M phase of the cell cycle suggesting an antimitotic action of these compounds. 相似文献
10.
Sangeetha Meenakshisundaram Manoj Manickam Thanigaimalai Pillaiyar 《Archiv der Pharmazie》2019,352(12)
Dimerization of proteins/receptors plays a critical role in various cellular processes, including cell proliferation and differentiation. Therefore, targeting such dimeric proteins/receptors by dimeric small molecules could be a potential therapeutic approach to treating various diseases, including inflammation‐associated diseases like cancer. A novel series of bis‐imidazoles ( 13–18 ) and bis‐imidazo[1,2‐a]pyridines ( 19–28 ) were designed and synthesized from Schiff base dimers ( 1–12 ) for their anticancer activities. All the synthesized compounds were screened for anticancer activities against three cancer cell lines, including cervical (HeLa), breast (MDA‐MB‐231), and renal cancer (ACHN). From structure–activity relationship studies, imidazo[1,2‐a]pyridines ( 19–28 ) showed remarkable cytotoxic activities, with compounds 19 and 24 showing the best inhibitory activities against all three cell lines. Especially, both 19 and 24 were very effective against the breast cancer cell line ( 19 , GI50 = 0.43 µM; 24 , GI50 = 0.3 µM), exceeding the activity of the control adriamycin (GI50 = 0.51 µM). The in vivo anticancer activity results of compounds 19 and 24 were comparable with those of the animals treated with the standard drug tamoxifen. Therefore, the dimeric imidazo[1,2‐a]pyridine scaffold could serve as a potential lead for the development of novel anticancer agents. 相似文献
11.
Synthesis and Biological Evaluation of Novel Carbohydrate‐Derived Derivatives of Erlotinib
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Preclinical Research |
12.
The cytotoxic activities of five new benzopyranone derivatives containing basic amino side chain are described. Their cytotoxicities against ER(+) MCF‐7 and ER(–) MDA‐MB‐231 human breast cancer cell lines, and Ishikawa human endometrial cell line were determined after 72 h drug exposure employing CellTiter‐Glo assay at concentrations ranging from 0.01–1.0 × 105 nM. The antiproliferative activities of these compounds were compared to tamoxifen (TAM), 4‐hydroxytamoxifen (4‐OHT, active metabolite of tamoxifen), and raloxifene (RAL). In‐vitro results indicated that compounds 9 , 10 , 12 , and 13 were more potent than TAM against the human breast cancer cell lines with IC50 < 20 µM. The in‐silico structure–activity relationships of these compounds and their binding mode within the estrogen receptor (ER) binding site using AutoDock vina are discussed. 相似文献
13.
Yunyun Wang Zhonglong Wang Hongbo Kuang Yan Zhang Wen Gu Yongqiang Zhu Shifa Wang 《Chemical biology & drug design》2019,94(1):1281-1291
A series of novel 2‐isocamphanyl thiosemicarbazone derivatives were synthesized and characterized by 1H NMR, 13C NMR, and HRMS. In in vitro anticancer activity, most derivatives showed considerable cytotoxic activity against four cancer cell lines (RPMI‐8226, A549, MDA‐MB‐231, and HepG2 cancer cells) and showed low toxicity against human gastric mucosal cells (GES‐1). Among them, compound 4h exhibited excellent antitumor activity against the tested cancer cells with IC50 values of 0.4, 1.1, 1.6, and 1.7 μM for MDA‐MB‐231, RPMI‐8226, A549, and HepG2, respectively. Further, mechanism studies indicated that compound 4h induced apoptosis in MDA‐MB‐231 cells through enhancing reactive oxygen species levels, inducing mitochondrial membrane potential decrease, and influencing the expression of Bax, Bcl‐2, caspase‐3, and caspase‐9. 相似文献
14.
《Chemical biology & drug design》2018,92(1):1373-1381
In this work, a wide range of novel quinazolin‐4(3H)‐one linked to 1,2,3‐triazoles was designed, synthesized, and evaluated against a panel of three human breast (MDA‐MB‐231, MCF‐7, T‐47D), lung (A549), and prostate (PC3) cancer cell lines. Our results revealed that the anticancer activity of the synthesized compounds was selectively affected by the presence of methoxy group on the linker between quinazolinone and 1,2,3‐triazole moieties. According to the calculated IC50 values, compounds 6q , 6w , and 6x showed good cytotoxicity against breast cancer cell lines even more effective than the reference drug, etoposide. Compounds 6q and 6u were found to be potent compounds against A549, non‐small‐cell lung cancer (NSCLC), comparing with erlotinib. Also, the morphological analysis by acridine orange/ethidium bromide double staining test and flow cytometry analysis indicated that potent compounds induced apoptosis in human cancer cell lines. Molecular docking studies were performed to clarify the inhibition mode of compounds 6g , 6u , 6w , and 6x over the EGFR active site. The most promising compounds, 6q and 6u , possessing 3‐methoxy group were well oriented to the gatekeeper hydrophobic pocket of EGFR active site and interact well with Ala719, Val702, and Leu820 through hydrophobic interaction. 相似文献
15.
Aurora Molinari Alfonso Oliva Claudia Ojeda José M. Miguel del Corral M. Angeles Castro Carmen Cuevas Arturo San Feliciano 《Archiv der Pharmazie》2009,342(10):591-599
Several new 6‐(3‐pyrazolylpropyl) derivatives of 1,4‐naphthohydroquinone‐1,4‐diacetate (NHQ‐DA) have been prepared by chemical modifications of the Diels–Alder adduct of α‐myrcene and 1,4‐benzoquinone. All these new compounds and precursors have been evaluated in vitro for their cytotoxicity against cultured human cancer cells of MB‐231 breast‐adeno carcinoma, A‐549 lung carcinoma, and HT‐29 colon carcinoma. GI50 values ranged in and below the micromolar concentration level. 相似文献
16.
Brien KA Bandi RK Behera AK Mishra BK Majumdar P Satam V Savagian M Tzou S Lee M Zeller M Robles AJ Mooberry S Pati H Lee M 《Archiv der Pharmazie》2012,345(5):341-348
Two divergent series of novel chalcone analogs, one derived from 1‐cyclohexylpyrrolidin‐2‐one and the other derived from 1‐benzo[f]chromanone, were designed, synthesized and evaluated for cytotoxicity against two murine cancer cell lines. Two 1‐benzo[f]chromanone analogs, 4g and 4j yielded moderate toxicity against both melanoma B16 and lymphoma L1210 cell lines with IC50 values between the range of 5 and 6 µM. With an IC50 value of 3.4 µM, compound 4g was also active against human MDA‐MB‐435 melanoma cells. X‐ray structures of the β‐hydroxy ketone product ( 4a ) and the α,β‐unsaturated ketone ( 4h ) were collected, and confirm the syn‐configuration between the carbonyl moiety and the β‐vinylic proton in 4h . X‐ray structures of two 1‐cyclohexylpyrrolidin‐2‐one derivatives were also obtained, and both showed an E‐configuration for the double bond. 相似文献
17.
Ju Liu Yutong Liu Xuechen Hao Yang Wang Jingchao Ji Yajing Liu Shi Ding Ye Chen 《Archiv der Pharmazie》2019,352(5)
A series of novel 4‐phenoxypyridine derivatives containing the 4‐oxo‐1,4‐dihydropyridazine‐3‐carboxamide moiety were synthesized and evaluated for their in vitro cytotoxic activity against the A549 cancer cell line, and some compounds were further examined for their cytotoxic activity against the H460, BGC823, MKN45, and HT‐29 cancer cell lines. Most of the compounds exhibited moderate to significant cytotoxicity. The most promising compound 15b (with VEGFR2 inhibitory concentration [IC50] value of 0.23 μM) showed remarkable cytotoxicity against A549, BGC‐823, MKN45, H460, and HT‐29 cells, with IC50 values of 0.75, 1.68, 2.63, 5.08 and 7.22 μM, respectively. Their preliminary structure‐activity relationship studies indicate that electron‐withdrawing groups on the terminal phenyl rings are beneficial for improving the antitumor activity. Moreover, treatment of A549 cells with compound 15b resulted in cell cycle arrest in the G0/G1 phase in a dose‐dependent manner. Further apoptotic studies and acridine orange/ethidium bromide staining were also performed on A549 cells, which showed that compound 15b could induce apoptosis. Wound‐healing assay results indicated that compound 15b strongly inhibited A549 cell motility. 相似文献
18.
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)
19.
Danuta Drozdowska Malgorzata Rusak Wojciech Miltyk Krystyna Midura‐Nowaczek 《Archiv der Pharmazie》2009,342(2):87-93
Eight of analogues of distamycin, potential minor‐groove binders, were synthesized and tested for in‐vitro cytotoxicity towards human breast cancer cells MCF‐7 and MDA‐MB‐231. The method of synthesis is simple and convenient. All of the compounds 1 – 8 showed antiproliferative and cytotoxic effects against both cell lines in the range 3.47 to 12.53 μM for MDA‐MB‐231 and 4.35 to 12.66 μM for MCF‐7. All compounds demonstrated activity against DNA topoisomerases I and II at a concentration of 50 μM. The ethidium bromide assay showed that these compounds bind to plasmid pBR322, yet weaker than distamycin. Further investigations concerning the mechanism of cytotoxicity are now in progress, but the IC50 values suggest that synthetic distamycin analogues with a free amino group, 3 – 4 and 7 – 8 , can serve as potential carriers of strong acting elements, e. g. alkylating groups. 相似文献
20.
Synthesis and biological evaluation of novel imidazopyrimidin‐3‐amines as anticancer agents
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Mohammad Mahdavi Shima Dianat Behnaz Khavari Setareh Moghimi Mohammad Abdollahi Maliheh Safavi Arash Mouradzadegun Sussan Kabudanian Ardestani Reyhaneh Sabourian Saeed Emami Tahmineh Akbarzadeh Alireza Foroumadi 《Chemical biology & drug design》2017,89(5):797-805
Groebke–Blackburn–Bienayme reaction has been utilized for the synthesis of new imidazo[1,2‐a]pyrimidine derivatives as novel anticancer agents. The cytotoxic activities of compounds were evaluated against human cancer cell lines including MCF‐7, T‐47D, and MDA‐MB‐231, compared with etoposide as the standard drug. Among the tested compounds, hydroxy‐ and/or methoxy‐phenyl derivatives ( 6a–c and 6k ) with IC50 values of 6.72–14.36 μm were more potent than etoposide against all cell lines. The acridine orange/ethidium bromide double staining and DNA fragmentation studies demonstrated that the cytotoxic effect of 3‐hydroxy‐4‐methoxyphenyl derivative 6c is associated with apoptosis in cancer cells. 相似文献