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1.
《Bioorganic & medicinal chemistry letters》2020,30(4):126896
A series of novel 3-benzylcoumarin-imidazolium salts were prepared and evaluated in vitro against a panel of human tumor cell lines. The results showed that the existence of 5,6-dimethyl-benzimidazole ring and substitution of the imidazolyl-3-position with a naphthylacyl group were vital for modulating cytotoxic activity. Notably, compound 38 was found to be the most potent derivative with IC50 values of 2.04–4.51 μM against five human tumor cell lines, while compound 34 were more selective to SW-480 cell lines with IC50 value 40.0-fold lower than DDP. Mechanism of action studies indicated that compound 38 can cause the G0/G1 phase cell cycle arrest and apoptosis in SMMC-7721 cell lines. 相似文献
2.
《Bioorganic & medicinal chemistry letters》2020,30(13):127210
A series of novel bisbenzofuran-imidazolium salts were designed and prepared. The in vitro antitumor activity of these derivatives was evaluated against a panel of human tumor cell lines (A549, HL-60, MCF-7, SMMC-7721 and SW480). Results demonstrated that 2-methyl-benzimidazole ring and substitution of the imidazolyl-3-position with a 4-methoxyphenacyl or 2-naphthylacyl substituent were important for promoting cytotoxic activity. Notably, compound 23 was found to be the most potent compound with IC50 values of 0.64–1.47 μM against five human tumor cell lines, and exhibited higher selectivity to MCF-7 and SW-480 cell lines with IC50 values 15.3-fold and 9.1-fold lower than DDP. 相似文献
3.
Sheng-Jiao Yan Chao Huang Xiang-Hui Zeng Rong Huang Jun Lin 《Bioorganic & medicinal chemistry letters》2010,20(1):48-51
A series of polyhalo heterocyclic ketene aminals (polyhalo-HKAs) were synthesized under solvent-free conditions and evaluated in vitro against a panel of human tumor cell lines. Trifluoro-HKAs were the most cytotoxic compounds, followed by difluoro-HKAs and trichloro-HKAs. Trichloro-HKAs were more potent against the tumor cell lines Skov-3, Hep-2, K562, and A431 than difluoro-HKAs. An ethoxycarbonyl at the 2-position of the polyhalo HKAs gave the highest activity. Ethoxycarbonyl substituted 5o, bearing three fluorine atoms on the isophthalonitrile ring, was found to be the most potent derivative with IC50 values lower than 3.7 μg/mL against five human tumor cell lines making it more active than cisplatin (DDP). 相似文献
4.
A new series of DNA-interactive β-carboline–chalcone conjugates have been synthesized and evaluated for their in vitro cytotoxicity and DNA-binding affinity. It has been observed that most of these new hybrids have shown potent cytotoxic activities on A-549 (lung adenocarcinoma) cell lines with IC50 values lower than 10 μM. The hybrid 7b is more effective against some of the selected cancer cell lines with IC50 values less than 50 μM. In addition, compounds 7e, 7k, 7p–u has displayed significant elevation in ΔTm of DNA in comparison to Adriamycin, suggesting significant interaction and remarkable DNA stabilization. The DNA intercalation of these new hybrids has been investigated by fluorescence titration, DNA viscosity measurements, molecular docking as well as molecular dynamics and the results are in agreement with the thermal denaturation studies. 相似文献
5.
Wen Chen Xiao-Yan Deng Yan Li Li-Juan Yang Wei-Chao Wan Xue-Quan Wang Hong-Bin Zhang Xiao-Dong Yang 《Bioorganic & medicinal chemistry letters》2013,23(15):4297-4302
A series of novel hybrid compounds of 2-phenyl-3-alkylbenzofuran and imidazole or triazole were prepared and evaluated in vitro against a panel of human tumor cell lines. The results suggest that the 2-ethyl-imidazole ring, and substitution of the imidazolyl-3-position with a 2-bromobenzyl or naphthylacyl group, were vital for modulating inhibitory activity. In particular, hybrid compound 31 was found to be the most potent derivative with IC50 values of 0.08–0.55 μM against five strains human tumor cell lines and was found to be more selective against breast carcinoma (MCF-7) and colon carcinoma (SW480) (IC50 values 40.8-fold and 40.1-fold lower than cisplatin (DDP)). 相似文献
6.
Jinrun Dong Xingrong Peng Lei Li Shuangyang Lu Lin Zhou Minghua Qiu 《Bioorganic & medicinal chemistry letters》2018,28(9):1520-1524
Eight new C21 steroidal glycosides, namely cynanotins A–H (1–8), together with fifteen known analogues, were isolated from the roots of Cynanchum otophyllum. Their structures were elucidated by spectroscopic analysis and chemical methods. In this study, all of isolates were tested for their vitro inhibitory activities against five human tumor cell lines (HL-60, SMMC-7721, A-549, MCF-7 and SW480). Compounds 3–15 showed moderate cytotoxic activities against HL-60 cell lines with IC50 values ranging from 11.4 to 37.9?µM. Compounds 5, 9, and 10 showed marked or moderate cytotoxic activities against five human tumor cell lines with IC50 values ranging from 11.4 to 36.7?µM. Compound 11 displayed moderate cytotoxic activities against HL-60, SMMC-7721, MCF-7 and SW480 cell lines with IC50 values of 12.2–30.8?µM. Compared to the positive control (IC50: 35.0?µM), compounds 5, 9–11 exhibited more potential inhibitory activity against MCF-7 cells (IC50: 16.1–25.6?µM). 相似文献
7.
Wei Shi Jinglin Hu Na Bao Dongang Li Li Chen Jianbo Sun 《Bioorganic & medicinal chemistry letters》2017,27(2):147-151
12 novel scopoletin-isoxazole and scopoletin-pyrazole hybrids were designed, synthesized and their chemical structures were confirmed by HR-MS, IR, 1H NMR and 13C NMR spectra. The anticancer activities of the newly synthesized compounds were evaluated in vitro against three human cancer cell lines including HCT-116, Hun7 and SW620 by MTT assay. The screening results showed that six compounds (9a, 9c, 9d, 12a, 18b and 18d) exhibited potent cytotoxic activities with IC50 values below 20 μM. Besides, we have further evaluated the growth inhibitory activities of six compounds against the human normal tissue cell lines HFL-1. Especially, compound 9d displayed significant anti-proliferative activity with IC50 values ranging from 8.76 μM to 9.83 μM and weak cytotoxicity with IC50 value of 90.9 μM on normal cells HFL-1, which suggested that isoxazole-based hybrids of scopoletin were an effective chemical modification to improve the anticancer activity of scopoletin. 相似文献
8.
Xiao-Dong Yang Xiang-Hui Zeng Yan-Li Zhang Chen Qing Wen-Jian Song Liang Li Hong-Bin Zhang 《Bioorganic & medicinal chemistry letters》2009,19(7):1892-1895
A series of novel phenacylimidazolium derivatives, bearing an aryl or alkyl substituent at position-1 and a phenacyl substituent at position-3 of the imidazole ring, has been prepared and evaluated in vitro against a panel of human tumor cell lines. Phenacylimidazolium bromides bearing a highly sterically hindered aryl group at position-1 and an electron-rich phenacyl or naphthylacyl substituent at position-3 of imidazole ring proved to be more active than imidazolium bromides with other substituted groups. In particular, compound 5j was found to be the most potent compounds with IC50 values lower than 5.0 μM against 8 strains human tumor cell lines and more active than cisplatin (DDP). 相似文献
9.
Yifeng Yang Yingxiu Li Yunlei Hou Mingze Qin Ping Gong Ju Liu Yanfang Zhao 《Bioorganic & medicinal chemistry letters》2019,29(23):126666
A series of novel 4-phenoxyquinoline derivatives containing 3-oxo-3,4-dihydro-quinoxaline moiety were synthesized and evaluated for their antiproliferative activity against five human cancer cell lines (A549, H460, HT-29, MKN-45 and U87MG) in vitro. Most of the tested compounds exhibited more potent inhibitory activities than the positive control foretinib. Compound 1b, 1s and 1t were further examined for their inhibitory activity against c-Met kinase. The most promising compound 1s (with c-Met IC50 value of 1.42 nM) showed remarkable cytotoxicity against A549, H460, HT-29, MKN45 and U87MG cell lines with IC50 values of 0.39 μM, 0.18 μM, 0.38 μM, 0.81 μM, respectively. Their preliminary structure-activity relationships (SARs) study indicated that the replacement of the aromatic ring with the cyclohexane improved their antiproliferative activity. 相似文献
10.
A series of novel N-hydroxypropenamides containing adamantane moiety were identified and most of them exhibited HDAC inhibitory activity and could reverse the resistance of cisplatin in NSCLC cell lines. In this process, molecular docking was employed to verify the rationality of designing, subsequently, target compounds were synthesized and conducted to enzyme- and cell-based biological evaluation. Most of synthesized compounds could inhibit HDAC activity with the IC50 values lower than 50 nM and result in the increase of Ac-H4 and p21 in A549 cells. Importantly, we assessed the reversal effect of those compounds and found several compounds display an anti-resistant effect in lung cancer cells, especially compound 8f.As compared to belinostat and cisplatin, compound 8f showed improved inhibitory activity against A549/CDDP cell lines with IC50 value of 5.76 μM, and far lower resistance index of 1.24. Moreover, the structure–activity relationships of these compounds were summarized and compound 8f could serve as a research tool for identifying the mechanism of reversing resistance and a template for designing novel compounds to reverse cisplatin resistance. 相似文献
11.
Zewei Mao Yan Li Jingbo Chen Yuanyuan Wang Hongbin Zhang 《Bioorganic & medicinal chemistry letters》2010,20(14):4116-4119
In this work, 23 new amides (14–36) bearing a representative diterpenoid structure unit, the functionalized bicyclo[3.2.1]octane ring, have been synthesized and its antitumor potential is studied. In vitro studies demonstrate that a number of amides with the bicyclo[3.2.1]oct-3-en-2-one subunit are active against HL-60, SMMC-7721, A-549, SK-BR-3, and PANC-1 tumor cell lines. The hybrid derivative, compound 20, was found to be the most potent compound (IC50 = 1.05 μM against HL-60) and more active than cisplatin (DDP), the positive control. Additionally, compound 20 exhibited broad spectrum in vitro anticancer activity with IC50 values of 1.1–4.3 μM against the five tested cancer cell lines. 相似文献
12.
Li L Zhao XT Luo YP Zhao JF Yang XD Zhang HB 《Bioorganic & medicinal chemistry letters》2011,21(24):7431-7433
Two novel flavonoids with chalcone skeleton, together with seven known flavonoids, were isolated from the stem barks of Litsea rubescens and Litsea pedunculata. The structures of the new compounds were elucidated on the basis of spectral methods including IR, UV, 1D and 2D NMR. The new chalcones were found to contain the rare epoxy or ethylidenedioxy group. This is the first report on the presence of chalcone in the plant genus Litsea. The cytotoxic potential of two new chalcones was evaluated in vitro against three human tumor cell lines. Both new chalcones displayed potent cytotoxic activities against myeloid leukaemia (HL-60) and epidermoid carcinoma (A431) cell lines and more active than cisplatin (DDP). Interestingly, compound 1 exhibited cytotoxic activity against HL-60 with IC50 value 2.1-fold more sensitive to DDP. 相似文献
13.
Six new (1–6) and nine known (7–15) staurosporine derivatives were isolated from the rice solid fermentation of the marine-derived Streptomyces sp. NB-A13. The structures of the new staurosporine derivatives were established by extensive spectroscopic data interpretation. The absolute configurations of 1 and 2 were assigned by quantum chemical calculations of the electronic circular dichroism (ECD) spectra. All of these compounds were screened for their cytotoxic activities against PC-3 and SW-620 cell lines. Compound 7 exhibited stronger inhibitory activity against SW-620 cell lines than the positive control staurosporine (25.10 nM), with IC50 values of 9.99 nM. Moreover, compounds 1–5, 8–13 and 15 also showed significant cytotoxicities with IC50 values ranging from 0.02 to 16.60 μM, while 6 exhibited no cytotoxic potency. Additionally, compounds 1–7 were also tested for enzyme inhibition activities of Protein kinase C theta (PKC-θ), and showed activity with IC50 values ranging from 0.06 to 9.43 μM except for compound 6, which has no inhibition activity. 相似文献
14.
Two new glycoalkaloids, erianosides A (1) and B (2) along with five known compounds (3–7) were isolated from the leaves of Solanum erianthum. Their structures were elucidated from analyses of spectroscopic data and all isolates were tested for in vitro cytotoxic activity against human breast cancer cell lines (BT-549, MDA-MB-231, T74D, and MCF-7). Solasonine (5) and solamargine (6) were active against the aforementioned four cancer cell lines with IC50 values of 27.26–35.89 and 5.84–10.13 μM, respectively. Erianoside A (1) (T74D: IC50, 56.39 µM) and solasodine (3) (BT-549 and MDA-MB-231: IC50, 59.15 and 75.63 µM, respectively) had moderate cytotoxic effects towards some cell lines in the panel. 相似文献
15.
A novel series of pyrazolo[1,5-a]pyrimidines were synthesized and proved by their spectral and elemental analysis, some elected of the newly synthesized compounds were examined for their cytotoxic activity employing MTT assay on two cancer cell lines (Breast and Hela cancers). Compounds 5, 7e and 7i showed the higher cytotoxicity against two cancer cell lines with (IC50 = 13.91 ± 1.4 and 22.37 ± 1.8 μM/L), (IC50 = 6.56 ± 0.5 and 8.72 ± 0.9 μM/L) and (IC50 = 4.17 ± 0.2 and 5.57 ± 0.4 μM/L) for two cancer cell lines breast and hela respectively, using doxorubicin as a reference drug. The most potent cytotoxic active compounds 5, 7e and 7i presented inhibitory activity against KDM (histone lysine demethylases) with IC50 = 4.05, 1.91 and 2.31 μM, respectively. The most potent KDM inhibitor 7e (IC50 = 1.91 μM) showed to cause cell cycle arrest at G2/M phase by 4 folds than control and induce total apoptotic effect by 10 folds more than control. In silico studies performed on the more potent cytotoxic active compounds 5, 7e and 7i included lipinisk's rule of five. Moreover, molecular docking study was utilized to explore the binding mode of the most active compounds to the target enzyme (PDB-ID: 5IVE). Also, some bioinformatics studies were carried out for compounds 7e and 7i using Swiss ADME (Swiss Institute of bioinformatics 2018). 相似文献
16.
《Bioorganic & medicinal chemistry letters》2020,30(22):127537
Several novel indirubin-based N-hydroxybenzamides, N-hydropropenamides and N-hydroxyheptanamides (4a-h, 7a-h, 10a-h) were designed using a fragment-based approach with structural features extracted from several previously reported HDAC inhibitors, such as SAHA (vorinostat), MGCD0103 (mocetinostat), nexturastat A and PXD-101 (belinostat). The biological results reveal that our compounds showed excellent cytotoxicity toward three common human cancer cell lines (SW620, PC-3 and NCI-H23) with IC50 values ranging from 0.09 to 0.007 µM. The cytotoxicity of the compounds was equipotent or even up to 10-times more potent than adriamycin and up to 205-times more potent than SAHA. Among the series of N-hydroxypropenamides, compounds 10a-d were the most potent HDAC inhibitors as well as cytotoxicity toward the cell lines tested. In addition, the strong inhibitory activites toward HDAC of our compounds were observed with IC50 values of below-micromolar range. Especially, compound 4a inhibited HDAC6 with an IC50 value of 29-fold lower than that against HDAC2 isoform. Representative compounds 4a and 7a were found to significantly arrest SW620 cells at G0/G1 phase. Compounds 7a and 10a were found to strongly induce apoptosis in SW620 cells. Docking studies revealed some important features affecting the selectivity against HDAC6 isoform. The results clearly demonstrate the potential of the indirubin-hydroxamic acid hybrids and these compounds should be very promising for further development. 相似文献
17.
A series of diindolylmethanes (5a-t) were designed, synthesized, and examined for their cytotoxicity against four human cancer cell lines like prostate (DU-145), lung (A549), breast (MCF-7) and cervical cancer (HeLa). These results revealed that among all the hybrids, two (5k and 5r) were identified and exhibited significant cytotoxic effect against A549 cancer cells with IC50 values of 1.65 ± 0.3 and 1.80 ± 0.8 µM respectively. To investigate the reasons for the cytotoxic activity, the conventional biological assays were carried out with 5k and 5r on the A549 cancer cells. Both hybrids led to the arrest of A549 cell lines at the G2/M phase of the cell cycle and strongly induced apoptosis. Further the apoptotic effects of 5k and 5r were confirmed by ROS, annexin-V FITC, and mitochondrial membrane potential. Moreover, structure–activity relationships were elucidated with various substitutions on these hybrids. 相似文献
18.
Suresh Kasaboina Venkatesh Ramineni Saleha Banu Yadagiri Bandi Lingaiah Nagarapu Naresh Dumala Paramjit Grover 《Bioorganic & medicinal chemistry letters》2018,28(4):664-667
A novel series of substituted pyrazolo-quinoline derivatives 7pa–7qg were synthesized efficiently by using molecular iodine in DMSO and further characterized based on 1H NMR, 13C NMR, IR and HRMS spectral studies. All the synthesized derivatives were screened for their in vitro cytotoxic activity against a panel of five different cancer cell lines such as A549, HeLa, SKNSH, HepG2 and MCF7. The compounds 7pc, 7pd, and 7pj exhibited considerable to promising anti-proliferative activity with IC50 values of 3.76, 3.87 and 3.83?µM against SKNSH cancer cell line. It was revealed that the compounds 7pa and 7pg have shown very close IC50 values of 2.43 and 6.01?µM, against A549 and MCF7 cancer cell lines respectively, which compared to positive control of Doxorubicin. This is the first report on the synthesis and in vitro anti-proliferative evaluation of pyrazolo-quinoline derivatives. 相似文献
19.
A series of novel benzotriazole N-acylarylhydrazone hybrids was synthesized according fragment-based design strategy. All the synthesized compounds were evaluated for their anticancer activity against 60 human tumor cell lines by NCI (USA). Five compounds: 3d, 3e, 3f, 3o and 3q exhibited significant to potent anticancer activity at low concentrations. Compound 3q showed the most prominent broad-spectrum anticancer activity against 34 tumor cell lines, with mean growth inhibition percent of 45.80%. It exerted the highest potency against colon HT-29 cell line, with cell growth inhibition 86.86%. All leukemia cell lines were highly sensitive to compound 3q. Additionally, compound 3q demonstrated lethal activity to MDA-MB-435 belonging melanoma. Compound 3e exhibited the highest anticancer activity against leukemic CCRF-CEM and HL-60(TB) cell lines, with cell growth inhibition 86.69% and 86.42%, respectively. Moreover, it exerted marked potency against ovarian OVCAR-3 cancer cell line, with cell growth inhibition 78.24%. Four compounds: 3d, 3e, 3f and 3q were further studied through determination of IC50 values against the most sensitive cancer cell lines. The four compounds exhibited highly potent anticancer activity against ovarian cancer OVCAR-3 and leukemia HL-60 (TB) cell lines, with IC50 values in nano-molar range between 25 and 130 nM. They showed 18–2.3 folds more potent anticancer activity than doxorubicin. The most prominent compound was 3e, (IC50 values 29 and 25 nM against OVCAR-3 and HL-60 (TB) cell lines, respectively), representing 10 and 18 folds more potency than doxorubicin. The anti-proliferative activity of these four compounds appeared to correlate well with their ability to inhibit FAK at nano-molar range between 44.6 and 80.75 nM. Compound 3e was a potent, inhibitor of FAK and Pyk2 activity with IC50 values of 44.6 and 70.19 nM, respectively. It was 1.6 fold less potent for Pyk2 than FAK. Additionally, it displayed inhibition in cell based assay measuring phosphorylated-FAK (IC50 = 32.72 nM). Inhibition of FAK enzyme led to a significant increase in the level of active caspase-3, compared to control (11.35 folds), accumulation of cells in pre-G1 phase and annexin-V and propidium iodide staining in addition to cell cycle arrest at G2/M phase indicating that cell death proceeded through an apoptotic mechanism. 相似文献
20.
A new series of 1,3,4-oxadiazole/chalcone hybrids was designed, synthesized, identified with different spectroscopic techniques and biologically evaluated as inhibitors of EGFR, Src, and IL-6. The synthesized compounds showed promising anticancer activity, particularly against leukemia, with 8v being the most potent. The synthesized compounds exhibited strong to moderate cytotoxic activities against K-562, KG-1a, and Jurkat leukemia cell lines in MTT assays. Compound 8v showed the strongest cytotoxic activity with IC50 of 1.95 µM, 2.36 µM and 3.45 µM against K-562, Jurkat and KG-1a leukemia cell lines, respectively. Moreover; the synthesized compounds inhibited EGFR, Src, and IL-6. Compound 8v was most effective at inhibiting EGFR (IC50 = 0.24 μM), Src (IC50 = 0.96 μM), and IL-6 (% of control = 20%). Additionally, most of the compounds decreased STAT3 activation. 相似文献