共查询到20条相似文献,搜索用时 15 毫秒
1.
Chun-Gu Wang Wei-Na Yao Bin Zhang Jing Hua Dong Liang Heng-Shan Wang 《Bioorganic & medicinal chemistry letters》2018,28(14):2413-2417
Cancer metastasis has been a major impediment to effective cancer treatment and is the major cause of cancer-related death. Polyphenols compounds have been reported to possess anti-metastasis activity through their inhibitory activity of matrix metalloproteinases (MMPs). In this paper, twelve polyphenols compounds, including three novel phenols, named selaphenins A–C (1–3), two known selaginellin derivatives (4 and 5), together with seven known biflavonoids (6–12) were isolated from the plant of Selaginella tamariscina. Their structures were elucidated by extensive spectroscopic analyses. Notably, polyphenols compound 10 suppressed the migration of A549 cells by primary targeting MMP-9. The antitumor activity of compound 10 was possibly due to the induction of cell apoptosis through intrinsic apoptosis pathways, accompanied by increasing the expression of Bax and caspase-3 in a dose-dependent manner. This study provides evidence that polyphenols analogues from S. tamariscina as inhibitors of MMP-9 exhibited potential migration inhibition activities. 相似文献
2.
Hao Zhang Xuejian Wang Jing Mao Yongxue Huang Wenfang Xu Yu Duan Jian Zhang 《Bioorganic & medicinal chemistry》2018,26(15):4363-4374
On the basis of the strategy of “multifunctional drugs”, a series of novel matrix metalloproteinase inhibitors (MMPIs) containing benzofuroxan scaffold as a nitric oxide donor were designed, synthesized and evaluated. All synthesized compounds, especially 16a, exhibited potent MMP-2,9 inhibitory activities, anti-proliferative activities and could produce high levels of NO in Hela cells. They were also evaluated for both of their anti-invasion and anti-angiogenesis effects. Furthermore, compared with LY52, 16a demonstrated competitive antitumor activity in vivo. These hybrid NO-MMPIs might offer suitable scaffolds to develop valuable MMP inhibitors for the further discovery of novel anti-cancer drugs. 相似文献
3.
Xun Li Yazhou Wang Jifeng Wu Yonggang Li Qiang Wang Wenfang Xu 《Bioorganic & medicinal chemistry》2009,17(8):3061-3071
As our ongoing work, a series of peptidomimetic l-iso-glutamine derivatives derived from antineoplaston AS2–5 scaffold were prepared and their APN/CD13 and MMP-2 inhibitory activities were evaluated hereby. The results displayed that these compounds exhibited selective inhibition against APN as compared with MMP-2, with IC50 values in micromole range. Compounds A1 and A2 showed comparable APN inhibitory activities than the positive control bestatin. 相似文献
4.
Zhi-Hao Shi Nian-Guang Li Qian-Ping Shi Hao Tang Yu-Ping Tang Wei Li Lian Yin Jian-Ping Yang Jin-Ao Duan 《Bioorganic & medicinal chemistry letters》2013,23(5):1206-1211
Four series of acid amides were synthesized, and through measurement using a fluorogenic substrate assay with human recombinant MMP-1, MMP-2 and MMP-9, compound 3f showed considerable inhibitory activities against MMP-2, MMP-9 and the best selectivity over MMP-1. Preliminary structure–activity relationship analysis indicated that caffeic acid amides with electron-donating groups at para-position of amino phenyl group showed better inhibitory activities and selectivity than those with electron-withdrawing groups, and the presence of adjacent dihydroxy in the caffeoyl group was very important for the MMP-2 and MMP-9 inhibitory activities. 相似文献
5.
Two new compounds, including one meroterpenoid (1) and a polyketide derivative (2), along with six compounds (3−8), were isolated from the rice solid fermentation of Penicillium expansum GY618. The structures of these new compounds were elucidated through interpretations of spectroscopic data and highresolution electrospray ionization mass spectrometry. The absolute configurations of all new compounds were unambiguously established through the optical rotation or calculation of the ECD spectrum. All isolated compounds were evaluated for their antibacterial and antitumor activities. Compound 6 exhibited weak antitumor activity. 相似文献
6.
《Bioorganic & medicinal chemistry letters》2019,29(18):2632-2634
The colchicine site inhibitors (CSIs) displayed both antimitotic and vascular disrupting activities, therefore are promising potential antitumor agents. In this study, a series 1-phenyl-4,5-dihydro-2H-benzo[e]indazoles were found as new CSIs of which the bioactive configuration was locked. Among them, compounds C1 and C2 displayed the best activity, with tubulin polymerization IC50 of 3.4 and 1.5 μM, and growth IC50 of low nanomolar concentrations against human colon cancer cell lines. In addition, compound C1 showed excellent broad-spectrum antitumor activity in the NCI-60 Human Tumor Cell Lines Screen, encouraging further study of this antitumor compound. 相似文献
7.
《Bioorganic & medicinal chemistry letters》2020,30(2):126849
Honokiol is a natural bioactive neolignan and has been widely researched and structural modified as an anticancer agent. In this paper, 18 honokiol derivatives were synthesized and investigated for their antitumor activity. Among these, the promising compound 5a exhibited much higher anti-proliferative activity with IC50 value of 10.41 μM. Transwell assays showed that 5a could significantly inhibit the invasion and migration of I-10 cells at 2.5 μM, which was further confirmed by the western blotting experiments with down-regulation of the HIF-1α and its associated downstream proteins MMP-2 and MMP-9. Overall, these results provided useful suggestion for further structural optimization of honokiol derivatives. 相似文献
8.
Hui-ning Li Hui Wang Zhi-peng Wang Hai-ning Yan Miao Zhang Yang Liu Mao-sheng Cheng 《Bioorganic & medicinal chemistry》2018,26(14):4025-4033
In an attempt to arrive at a more potent antitumor agent than the parent natural saponin hederacolchiside A1, 23 hederacolchiside A1 derivatives (4a-4w) were synthesized via Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition and screened in vitro for cytotoxicity against six human cancer cell lines. The structure-activity relationship of these compounds was elucidated, and the biological screening results showed that most of the compounds exhibited moderate to high levels of antitumor activities against the tested cell lines and some of them displayed more potent inhibitory activities compared with hederacolchiside A1. Compound 4f showed a 2- to 7-fold more potent activity than hederacolchiside A1. The mechanistic study of 4f revealed that this compound can induce cell apoptosis in HepG2 cells via mitochondrial-mediated intrinsic pathways. 相似文献
9.
《Bioorganic & medicinal chemistry letters》2014,24(3):884-887
Two series of novel tricyclic oxazine and oxazepine fused quinazolines have been designed and synthesized. The in vitro antitumor effect of the title compounds was screened on N87, A431, H1975, BT474 and Calu-3 cell lines. Compared to erlotinib and gefitinib, compounds 1a–1h were found to demonstrate more potent antitumor activities. Several derivatives could counteract EGF-induced phosphorylation of EGFR in cells, and their potency was comparable to the reference compounds. Compounds 1a–1h were chosen for further evaluation of EGFR and HER2 in vitro kinase inhibitory activity. Compounds 1b–1f, 1h effectively inhibited the in vitro kinase activity of EGFR and HER2 with similar efficacy as erlotinib and gefitinib. 相似文献
10.
Satoshi Miyanaga Hiroaki Sakurai Ikuo Saiki Hiroyasu Onaka Yasuhiro Igarashi 《Bioorganic & medicinal chemistry》2009,17(7):2724-2732
Myxochelin A (1) is an inhibitor of tumor cell invasion produced by the bacterium belonging to the genus Nonomuraea. In order to obtain more potent inhibitors, a series of myxochelin analogues [2 and (S)-3–17] were synthesized through the coupling of lysine or diaminoalkane derivatives and appropriately protected hydroxybenzoate, followed by modification of functional groups and deprotection. These compounds were evaluated for their inhibitory activity against invasion of murine colon 26-L5 carcinoma cells. Among the synthetic analogues tested, compound (S)-6 which possesses carbamoyl group at C-1 was found to be the most potent antiinvasive agent and is considered to be a promising lead molecule for the antimetastasis. Compound (S)-6 was also shown to inhibit gelatinase activities of MMP-2 and MMP-9 and in vivo lung metastasis in mice. 相似文献
11.
2-Dimethylaminomethylene-1-benzosuberone 1 was coupled with diazotized aniline derivatives to afford a series of the hitherto unreported 2-arylazo-1-benzosuberones 3a–i. The tautomeric structure and the effect of substituents on the tautomeric form (s) of the products 3a–i were discussed. Similar coupling of the enaminone 1 with diazonium salts of heterocyclic amines gave the respective fused azolotriazino-benzosuberones. Some of the newly synthesized compounds showed potent antimicrobial, anti-HCV, antioxidant, antitumor (as topoisomerase I inhibitors), and antimicrobial activities. 相似文献
12.
《Bioorganic & medicinal chemistry letters》2014,24(6):1511-1518
A series of dipeptide derivatives from dehydroabietic acid were designed and synthesized as novel antitumor agents. The antitumor activities screening indicated that many compounds showed moderate to high levels of inhibition activities against NCI-H460, HepG2, SK-OV-3, BEL-7404, HeLa and HCT-116 cancer cell lines and that some displayed more potent inhibitory activities than commercial anticancer drug 5-fluorouracil. The mechanism of representative compound 7b was studied by AO/EB staining, Hoechst 33258 staining, JC-1 mitochondrial membrane potential staining, TUNEL assay, DNA ladder assay and flow cytometry, which exhibited that the compound could induce apoptosis in HeLa cells. Further investigation showed that compound 7b induced apoptosis of HeLa cells through a mitochondrial pathway. 相似文献
13.
Zhong-Chang Wang Fa-Qian Shen Meng-Ru Yang Ling-Xia You Li-Zhi Chen Hai-Liang Zhu Ya-Dong Lu Fan-Lei Kong Ming-Hua Wang 《Bioorganic & medicinal chemistry letters》2018,28(23-24):3816-3821
MMP-2/MMP-8 is established as one of the most important metalloenzymes for targeting cancer. A series of dihydropyrazothiazole derivatives (E1–E18) bearing a salicylaldehyde group linked to Pyrazole ring were designed, synthesized, and evaluated for their pharmacological activity as MMP-2/MMP-8 inhibitors. Among them, compound E17 exhibited most potent inhibitory activity (IC50?=?2.80?μM for MMP-2 and IC50?=?5.6?μM for MMP-8), compared to the positive drug CMT-1 (IC50?=?1.29?μM). Compounds (E1–E18) were scrutinized by CoMFA and CoMSIA techniques of Three-dimensional quant. structure-activity relationship (3D-QSAR), as well as a docking simulation. Moreover, treatment with compound E4 could induce MCF-7 cell apoptosis. Overall, the biological profile of E1–E18 may provide a research basis for the development of new agents against cancer. 相似文献
14.
Fang Liu Ziyou Huai Guotai Xia Liuping Song Sha Li Yulan Xu Kangjun Hong Mingyue Yao Gang Liu Yinjiu Huang 《Bioorganic & medicinal chemistry letters》2018,28(14):2561-2565
A series of 6,7,8-trimethoxy N-aryl-substituted-4-aminoquinazoline derivatives were synthesized as epidermal growth factor receptor (EGFR) inhibitors, and their antitumor activities were assessed in the gastric cancer cell line SGC7901 using MTT assay. All compounds of Tg1–14 were found to inhibit SGC7901 cell proliferation, and compound Tg11 (IC50?=?0.434?μM) was found to be slightly more effective against SGC7901 cells than epirubicin (IC50?=?5.16?μM). This suggests that compound Tg11 can be used as a new substitution structure to develop more efficacious antitumor agents. Western blot analysis showed that treatment with Tg11 (40?μM for 30?min) resulted in near complete inhibition of EGF-induced ERK1/2 phosphorylation, indicating that its anti-proliferative effect is largely associated with inhibition of ERK1/2 activation. These data imply that Tg11 is a potential anticancer agent capable of inhibiting cell proliferation. 相似文献
15.
Jiajia Mou Hao Fang Yingzi Liu Luqing Shang Qiang Wang Lei Zhang Wenfang Xu 《Bioorganic & medicinal chemistry》2010,18(2):887-895
A series of bi- or tri-peptide analogues with the scaffold l-arginine were designed, synthesized and evaluated for their inhibitory activities against amino-peptidase N (APN) and metalloproteinase-2 (MMP-2). The primary activity assay showed that all the compounds exhibited higher inhibitory activities against APN than MMP-2. Within this series, compounds C6 and C7 (IC50 = 4.2 and 4.3 μM) showed comparable APN inhibitory activities with the positive control bestatin (IC50 = 3.8 μM). 相似文献
16.
Jiansheng Lu Yihua Ma Jianjia Liang Yingying Xing Tao Xi Yuanyuan Lu 《Microbiological research》2012,167(10):590-595
A marine-derived actinomycete (Streptomyces sp. WBF16) exhibiting antitumor activities was investigated. The strain was identified using morphological, biochemical and genetic techniques. 16S rDNA sequence of the isolate indicated that it was most closely related to Streptomyces coelicolor A3 (2). Furthermore, a new aureolic acid (Chromomycin B, 1), along with Chromomycin A2 (2) and Chromomycin A3 (3) were isolated from its secondary metabolites. Their structures were determined by chemical and spectroscopic methods including 1D, 2D NMR and HRMS. Compounds 1–3 showed strong cytotoxicity against SGC7901, HepG2, A549, HCT116 and COC1 and HUVEC. 相似文献
17.
Jiajia Mou Hao Fang Fanbo Jing Qiang Wang Yingzi Liu Huawei Zhu Luqing Shang Xuejian Wang Wenfang Xu 《Bioorganic & medicinal chemistry》2009,17(13):4666-4673
A series of l-arginine derivatives were designed, synthesized and assayed for their activities against amino-peptidase N (APN)/CD13 and metalloproteinase-2 (MMP-2). The results showed that most compounds exhibited high inhibitory activities against APN and low activities against MMP-2. Within this series, two compounds 5q and 5s (IC50 = 5.3 and 5.1 μM) showed similar inhibitory activities compared with bestatin (IC50 = 3.8 μM), which could be used as novel lead compounds for the future APN inhibitors development as anticancer agents. 相似文献
18.
Kang-Yeoun Jung Jihyun Park Young-Sung Han Young Han Lee Soon Young Shin Yoongho Lim 《Bioorganic & medicinal chemistry》2017,25(1):397-407
A flavanone, hesperetin, has been known to exert antitumor activity by inducing apoptosis. To find hesperetin derivatives showing better antitumor activity, 12 derivatives were designed and synthesized. Their antitumor activities were measured using a long-term survival clonogenic assay. Among the compounds, K-5b, hesperetin-7-butyrate, showed the half-maximal cell growth inhibitory concentration three times as low as that of hesperetin. To compare the cytotoxicity of hesperetin and K-5b, the HCT116 human colon cancer cell line was treated with various concentrations of each compound. K-5b decreased the cell viability to a larger extent than hesperetin and triggered apoptosis more efficiently than hesperetin in an apoptosis detection assay using fluorescein isothiocyanate-labeled annexin V. Immunoblotting analysis showed that K-5b promoted caspase-mediated apoptosis more efficiently than hesperetin. Because hesperetin has been reported to induce apoptosis through the activation of the c-Jun N-terminal kinase (JNK) pathway, we tested whether K-5b activates JNKs. K-5b stimulated JNK1 and JNK2 more efficiently than hesperetin as shown by western blot analysis. In conclusion, hesperetin derivatives exerting better antitumor activity than hesperetin by inducing apoptosis were found. 相似文献
19.
Yonggang Li Jian Zhang Wenfang Xu Huawei Zhu Xun Li 《Bioorganic & medicinal chemistry》2010,18(4):1516-1525
A series of quinoxalinone peptidomimetic derivatives was designed, synthesized, and assayed for their inhibitory activities on metalloproteinase-2 (MMP-2) and aminopeptidase N (APN). The results showed that all of these quinoxalinone derivatives displayed highly selective inhibition against MMP-2 as compared with APN, with IC50 values in the micromole range. Compound A3 showed comparable MMP-2 inhibitory activities than the positive control LY52, which might be used as a potential lead in future research on anticancer agents. 相似文献
20.
A series of novel naphthalimide derivatives with flexible leucine side chains were designed and synthesized. Their antitumor activities were evaluated against HeLa, A549, P388, HL-60, MCF-7, HCT-8 and A375 cancer cell lines in vitro. The preliminary results showed that most of the derivatives had moderate antitumor activities with the IC50 values of 10?6–10?5 M. More importantly, compounds 8a–c exhibited exclusive antitumor activities against MCF-7 cell line. The interaction between compound 8b and BSA was also investigated. DNA binding experiments showed that these derivatives behaved as DNA intercalating agents. This work provided a novel class of naphthalimide-based lead compounds with exclusive antitumor activities against MCF-7 cell line for further optimization. 相似文献