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1.
Fangchao Bi Liwei Guo Yinhu Wang Henrietta Venter Susan J. Semple Fang Liu Shutao Ma 《Bioorganic & medicinal chemistry letters》2017,27(4):958-962
Novel series of 3-substituted 2,6-difluorobenzamide derivatives as FtsZ inhibitors were designed, synthesized and evaluated for their in vitro antibacterial activity against various phenotype of Gram-positive and Gram-negative bacteria, and their cell division inhibitory activity against three representative strains. As a result, 3-chloroalkoxy derivative 7, 3-bromoalkoxy derivative 12 and 3-alkyloxy derivative 17 were found to exhibit the best antibacterial activity against Bacillus subtilis with MICs of 0.25–1 μg/mL, and good activity (MIC < 10 μg/mL) against both susceptible and resistant Staphylococcus aureus. Additionally, all the three compounds displayed potent cell division inhibitory activity with MIC values of below 1 μg/mL against Bacillus subtilis and Staphylococcus aureus. 相似文献
2.
Sherine Nabil Khattab Nesreen Saied Haiba Ahmed Mosaad Asal Adnan A. Bekhit Aida A. Guemei Adel Amer Ayman El-Faham 《Bioorganic & medicinal chemistry letters》2017,27(4):918-921
A new small library of 2-aminobenzoyl amino acid hydrazide derivatives and quinazolinones derivatives was synthesized and fully characterized by IR, NMR, and elemental analysis. The activity of the prepared compounds on the growth of Leishmania aethiopica promastigotes was evaluated. 2-Benzoyl amino acid hydrazide showed higher inhibitory effect than the quinazoline counterpart. The in vitro antipromastigote activity demonstrated that compounds 2a, 2b, 2f and 4a had IC50 better than standard drug miltefosine and comparable activity to amphotericin B deoxycholate, which indicates their high antileishmanial activity against Leishmania. aethiopica. Among the prepared compounds; 2-amino-N-(6-hydrazinyl-6-oxohexyl)benzamide 2f (IC50 = 0.051 μM) has the best activity, 154 folds more active than reference standard drug miltefosine (IC50 = 7.832 μM), and half fold the activity of amphotericin B (IC50 = 0.035 μM). In addition, this compound was safe and well tolerated by experimental animals orally up to 250 mg/kg and parenterally up to 100 mg/kg. 相似文献
3.
Qing-Kun Shen Chuan-Feng Liu Hong-Jian Zhang Yu-Shun Tian Zhe-Shan Quan 《Bioorganic & medicinal chemistry letters》2017,27(21):4871-4875
Two series of xanthotoxin-triazole derivatives were designed, synthesized, and studied for their antiproliferative properties. The in vitro cytotoxicity of the compounds in the AGS cancer cell line and the L02 normal cell line was evaluated via MTT assay. Among the synthesized compounds, 9-((1-(4-(trifluoromethyl)phenyl)-1H-1,2,3-triazol-4-yl)methoxy)-7H-furo[3,2-g]chromen-7-one (6p) was found to have the greatest antiproliferative activity against AGS cells (IC50 = 7.5 μM) and showed better activity than the lead compound (xanthotoxin, IC50 > 100 μM) and the reference drug (5-fluorouracil, IC50 = 29.6 μM) did. The IC50 value of 6p in L02 cells was 13.3 times higher than that in the AGS cells. Therefore, the compound exhibited better therapeutic activity and specificity compared with the positive control 5-fluorouracil. Cell cycle analysis revealed that compound 6p inhibited cell growth via the induction of S/G2 phase arrest in AGS cells. Compound 6p was identified as a promising lead compound for the further development and identification of 1,2,3-triazole-based anticancer agents. 相似文献
4.
Bhadaliya Chetan Mahesh Bunha Monika Jagrat Barij Nayan Sinha Philipp Saiko Geraldine Graser Thomas Szekeres Ganapathy Raman Praveen Rajendran Dhatchana Moorthy Arijit Basu Venkatesan Jayaprakash 《Bioorganic & medicinal chemistry letters》2010,20(13):3906-3910
Six compounds were synthesized with piperazine in linker region and hydroxamate as Zinc Binding Group (ZBG). They were screened against three cancer cell-lines (NCIH460; HCT116; U251). Compounds 5c and 5f with GI50 value of 9.33 ± 1.3 μM and 12.03 ± 4 μM, respectively, were tested for their inhibitory potential on hHDAC8. Compound 5c had IC50 of 33.67 μM. Compounds were also screened for their anticancer activity against HL60 human promyelocytic leukemia cell line due to the presence of pharmacophoric features of RR inhibitors in them. Compound 5c had IC50 of 0.6 μM at 48 h. 相似文献
5.
Yuanying Fang Rikang Wang Mingzhen He Hesong Huang Qi Wang Zunhua Yang Yan Li Shilin Yang Yi Jin 《Bioorganic & medicinal chemistry letters》2017,27(1):98-101
A series of nitric oxide (NO) donating derivatives of hederacolchiside A1 bearing triterpenoid saponin motif were designed, synthesized and evaluated for their anticancer activity. All of the tested furoxan-based NO releasing compounds showed significant proliferation inhibitory activities. Especially compound 6a exhibited strong cytotoxicity (IC50 = 1.6–6.5 μM) against four human tumor cell lines (SMMC-7721, NCI-H460, U251, HCT-116) in vitro and the highest level of NO releasing. Furthermore, compound 6a was revealed low acute toxicity to mice and weak haemolytic activity with potent tumor growth inhibition against mice H22 hepatocellular cells in vivo (51.5%). 相似文献
6.
Shuting Chen Ying Zhang Xiaoyan Li Hongmei Jia Jie Lu 《Bioorganic & medicinal chemistry letters》2017,27(15):3551-3554
A triphenylphosphonium cation, [99mTc]Technetium cyclopentadienyltricarbonyl-6-hexanoyl-triphenylphosphonium cation ([99mTc]3) was prepared to target multidrug resistance (MDR). The radiotracer was evaluated in the MDR-negative MCF-7 and MDR-positive MCF-7/ADR cell lines in vitro, as well as animal models in vivo. [99mTc]3 was proofed to be a substrate of P-glycoprotein and multidrug resistant protein 1, and showed a higher accumulation in the MDR-negative MCF-7 cells compared to 99mTc-sestamibi in vitro. The MCF-7 tumor-to-MCF-7/ADR tumor ratio of [99mTc]3 was ~3 at 1 h p.i. in the biodistribution study. These results demonstrated the capability of the radiotracer to detect multidrug resistance in tumor cells. 相似文献
7.
P.O. Venkataramana Reddy Shriprada Mishra Mukund P. Tantak Kumar Nikhil Rachna Sadana Kavita Shah Dalip Kumar 《Bioorganic & medicinal chemistry letters》2017,27(6):1379-1384
A series of novel β-carbolinium bromides has been synthesized from easily accessible β-carbolines and 1-aryl-2-bromoethanones. The newly synthesized compounds were evaluated for their in vitro anticancer activity. Among the synthesized derivatives, compounds 16l, 16o and 16s exhibited potent anticancer activity with IC50 values of <10 μM against tested cancer cell lines. The most potent analogue 16l was broadly active against all the tested cancer cell lines (IC50 = 3.16–7.93 μM). In order to test the mechanism of cell death, we exposed castration resistant prostate cancer cell line (C4-2) to compounds 16l and 16s, which resulted in increased levels of cleaved PARP1 and AO/EB staining, indicating that β-carbolinium salts induce apoptosis in these cells. Additionally, the most potent β-carbolines 16l and 16s were found to inhibit tubulin polymerization. 相似文献
8.
《Bioorganic & medicinal chemistry》2014,22(21):5860-5870
To identify new potent multidrug resistance modulators, we have synthesized a series of novel thieno[2,3-b]pyridines and furo[2,3-b]pyridines, and examined their stucture–activity relationships. All synthesized compounds were tested to determine BCRP1, P-gp, and MRP1 inhibitor activity, and most potent MDR modulators were also screened for their toxicity, cytotoxicity and Ca2+ channel antagonist activity. Among these compounds, thieno[2,3-b]pyridine (6r) was found to exhibit a potent P-gp inhibitory action with EC50 = 0.3 ± 0.2 μM, MRP1 inhibitory action with EC50 = 1.1 ± 0.1 μM and BCRP1 inhibitory action with EC50 = 0.2 ± 0.05 μM and may represent suitable candidate for further pharmacological studies. 相似文献
9.
Cheng-Jie Yang Zi-Long Song Masuo Goto Pei-Ling Hsu Xiao-Shuai Zhang Qian-Ru Yang Ying-Qian Liu Mei-Juan Wang Susan L. Morris-Natschke Xiao-Fei Shang Kuo-Hsiung Lee 《Bioorganic & medicinal chemistry letters》2017,27(20):4694-4697
Fluorination is a well-known strategy for improving the bioavailability of bioactive molecules in the lead optimization phase of drug discovery projects. In an attempt to improve the antitumor activity of camptothecins (CPTs), novel 10-fluoro-CPT derivatives were designed, synthesized and evaluated for cytotoxicity against five human cancer cell lines (A-549, MDA-MB-231, KB, KB-VIN and MCF-7). All of the derivatives showed more potent in vitro cytotoxic activity than the clinical CPT-derived drug irinotecan against the tumor cell lines tested, and most of them showed comparable or superior potency to topotecan. Remarkably, compounds 16b (IC50, 67.0 nM) and 19b (IC50, 99.2 nM) displayed the highest cytotoxicity against the multidrug-resistant (MDR) KB-VIN cell line and merit further development as preclinical drug candidates for treating cancer, including MDR phenotype. Our study suggested that incorporation of a fluorine atom into position 10 of CPT is an effective method for discovering new potent CPT derivatives. 相似文献
10.
Wen-Xue Sun Ya-Jing Ji Yun Wan Hong-Wei Han Hong-Yan Lin Gui-Hua Lu Jin-Liang Qi Xiao-Ming Wang Yong-Hua Yang 《Bioorganic & medicinal chemistry letters》2017,27(17):4066-4074
In this paper, a series of podophyllotoxin piperazine acetate ester derivatives were synthesized and investigated due to their antiproliferation activity on different human cancer cell lines. Among the congeners, C5 manifested prominent cytotoxicity towards the cancer cells, without causing damage on the non-cancer cells through inhibiting tubulin assembly and having high selectively causing damage on the human breast (MCF-7) cell line (IC50 = 2.78 ± 0.15 μM). Treatments of MCF-7 cells with C5 resulted in cell cycle arrest in G2/M phase and microtubule network disruption. Moreover, regarding the expression of cell cycle relative proteins CDK1, a protein required for mitotic initiation was up-regulated. Besides, Cyclin A, Cyclin B1 and Cyclin D1 proteins were down-regulated. Meanwhile, it seems that the effect of C5 on MCF-7 cells apoptosis inducing was observed to be not obvious enough. In addition, docking analysis demonstrated that the congeners occupy the colchicine binding pocket of tubulin. 相似文献
11.
Aireen A. Romu Zining Lei Bin Zhou Zhe-Sheng Chen Vijaya Korlipara 《Bioorganic & medicinal chemistry letters》2017,27(21):4832-4837
A series of thirty two anilinopyrimidines derived from WZ4002 has been synthesized and evaluated for percentage inhibition of six different EGFR kinases using LanthaScreen binding assay method (EGFR d746 – 750) or Z’LYTE assay method (EGFR-WT, EGFR d746 – 750, EGFR T790M, EGFR T790M L858R, EGFR C797S and EGFR T790M L858R C797S). Ortho-hydroxyacetamide 10 exhibited complete inhibition of all the six kinases at 10 µM. Against the triple mutant, EGFR T790M C797S L858R, compounds 9–12 exhibited complete inhibition at 10 µM and nearly complete inhibition at 1 µM. The target compounds were also evaluated using the MTT assay to determine their cytotoxic activity against human non-small cell lung cancer cells (PC9, PC9GR and H460) and mouse leukemic cells (Ba/F3 WT and Ba/F3T 3151). Overall, 7, 9–12, 30 and 31 were found to be the most potent compounds across all five cell lines. 相似文献
12.
Yunyun Wang Wen Gu Yu Shan Fei Liu Xu Xu Yiqin Yang Qiangjian Zhang Yan Zhang Hongbo Kuang Zhonglong Wang Shifa Wang 《Bioorganic & medicinal chemistry letters》2017,27(11):2360-2363
A series of new nopinone-based thiosemicarbazone derivatives were designed and synthesized as potent anticancer agents. All these compounds were identified by 1H NMR, 13C NMR, HR-MS spectra analyses. In the in vitro anticancer activity, most derivatives showed considerable cytotoxic activity against three human cancer cell lines (MDA-MB-231, SMMC-7721 and Hela). Among them, compound 4i exhibited most potent antitumor activity against three cancer cell lines with the IC50 values of 2.79 ± 0.38, 2.64 ± 0.17 and 3.64 ± 0.13 μM, respectively. Furthermore, the cell cycle analysis indicated that compound 4i caused cell cycle arrest of MDA-MB-231 cells at G2/M phase. The Annexin V-FITC/7-AAD dual staining assay also revealed that compound 4i induced the early apoptosis of MDA-MB-231 cells. 相似文献
13.
Kali Charan Gulipalli Srinu Bodige Parameshwar Ravula Srinivas Endoori Nareshvarma Seelam 《Bioorganic & medicinal chemistry letters》2017,27(15):3558-3564
A series of novel methyl 4-(4-amidoaryl)-3-methoxythiophene-2-carboxylate derivatives were designed against the active site of protein tyrosine phosphatise 1B (PTP1B) enzyme using MOE.2008.10. These molecules are also subjected for in silico toxicity prediction studies and considering their corresponding drug scores, it implied that, the molecules are promising as anticancer agents. The designed compounds were synthesized by using suitable methods and characterized. They were subjected to inhibitory activity against PTP1B and in vitro anticancer activity by MTT assay. Most of the tested compounds showed potent inhibitory activity against PTP1B, among the compounds tested, compound 5b exhibited the highest activity (IC50 = 5.25 µM) and remarkable cytotoxic activity at 0.09 µM of IC50 against the MCF-7 cell line. In addition to this, compound 5c also showed potential anticancer activity at 2.22 µM of IC50 against MCF-7 and 0.72 µM against HepG2 cell lines as well as PTP1B inhibitory activity at IC50 of 6.37 µM. 相似文献
14.
Yang Hu Lei Liu Guang-Lu Liu Xiao Tu Gao-Xue Wang Fei Ling 《Bioorganic & medicinal chemistry letters》2017,27(15):3310-3316
To control the parasitic disease of Dactylogyrus intermedius, a series of new arctigenin derivatives were designed, synthesized and tested in our study. The anthelmintic activity of most of the derivatives ranged from 1 to 10 mg/L. Compared to traditional drug praziquantel (EC50 = 2.69 mg/L), ether derivatives 2g and 2h exhibited slightly higher anti-parasitic activity, with the EC50 values of 2.48 and 1.52 mg/L, respectively. Furthermore, the arctigenin-imidazole hybrids 4a and 4b also removed D. intermedius effectively, with the EC50 values of 2.13 and 2.07 mg/L, respectively. The structure-activity relationship analysis indicated that four carbon atoms length of linker and imidazole substitute group could significantly increase the anthelmintic activity, and reduced the toxicity. Through the scanning electron microscope observation, compounds 4a and 4b caused the D. intermedius tegumental damage such as intensive wrinkles, holes and nodular structures. Overall, the structural optimization analysis of arctigenin suggested that 4a and 4b can be used for preventing and controlling Dactylogyrus infections and considered as promising lead compounds for the development of commercial drugs. 相似文献
15.
Wen Gu Xiao-Yan Jin Dong-Dong Li Shi-Fa Wang Xu-Bing Tao Hao Chen 《Bioorganic & medicinal chemistry letters》2017,27(17):4128-4132
A series of new quinoline derivatives of ursolic acid were designed and synthesized in an attempt to develop potential anticancer agents. The structures of these compounds were identified by 1H NMR, 13C NMR, IR and ESI-MS spectra analysis. The target compounds were evaluated for their in vitro cytotoxicity against three human cancer cell lines (MDA-MB-231, Hela and SMMC-7721). From the results, compounds 3a–d displayed significant antitumor activity against three cancer cell lines. Especially, compound 3b was found to be the most potent derivative with IC50 values of 0.61 ± 0.07, 0.36 ± 0.05, 12.49 ± 0.08 μM against MDA-MB-231, HeLa and SMMC-7721 cells, respectively, stronger than positive control etoposide. Furthermore, the Annexin V-FITC/PI dual staining assay revealed that compound 3b could significantly induce the apoptosis of MDA-MB-231 cells in a dose-dependent manner. The cell cycle analysis also indicated that compound 3b could cause cell cycle arrest of MDA-MB-231 cells at G0/G1 phase. 相似文献
16.
Suresh Narva Surendar Chitti Suresh Amaroju Debanjan Bhattacharjee Bala Bhaskara Rao Nishant Jain Mallika Alvala Kondapalli Venkata Gowri Chandra Sekhar 《Bioorganic & medicinal chemistry letters》2017,27(16):3794-3801
A series of thirty-seven 1,3,5-triazine analogues have been synthesized, characterized and evaluated for their antiproliferative activity against a panel of four different human cancer cell lines such as HeLa, HepG2, A549 and MCF-7. Most of the 1,3,5-triazine analogues exhibited promising antiproliferative activity against tested cancer cell lines. Among all the synthesized compounds, 8j showed potent activity against the cancer cell lines such as HeLa, HepG2, A549 and MCF-7 with IC50 12.3 ± 0.8, 9.6 ± 0.4, 10.5 ± 1.0 and 11.7 ± 0.5 μM respectively. 8j was taken up for elaborate biological studies and the cells in the cell cycle were arrested in G2/M phase. In addition, 8j was examined for its effect on the microtubule system with a tubulin polymerization assay, immunofluorescence. 8j showed remarkable inhibition of tubulin polymerization. Molecular docking studies were also carried out to understand the binding pattern. The studies suggested that 8j has a good binding affinity of ?7.949 towards nocodazole binding site of tubulin while nocodazole has ?7.462. 相似文献
17.
Yanyan Sun Lei Chen Xiwen Wu Qian Ding 《Bioorganic & medicinal chemistry letters》2017,27(4):1070-1075
A series of ethylenediamine/1,3-propanediamine derivatives containing bifunctional bisphosphonate substituents and their corresponding dichloroplatinum(II) complexes have been synthesized and characterized by elemental analysis, 1H NMR, 13C NMR, 31P NMR, and HRMS spectra. Based on WST-8 assay with CCK-8, in general, the newly synthesized dichloroplatinum complexes 1–6 showed higher in vitro antitumor activity than platinum-free compounds L1–L6 against three tumor cell lines (especially osteosarcoma MG-63). According to hydroxyapatite binding experiment, complexes 2, 3, and 6 showed much higher affinity (K′ = 3.7, 4.0, and 3.0, respectively) for bone hydroxyapatite than cisplatin (K′ < 0.1), comparable to zoledronate (K′ = 2.8). It can be found that representative complex 2 with high cytotoxicity and in vitro antiproliferative activity against osteosarcoma cell line, as well as promising hydroxyapatite binding ability has been screened as a potential bone-targeting antitumor agent for subsequent in vivo study. In addition, flow cytometry experiment was applied to investigate the mode of action of representative complex 2. 相似文献
18.
Fa-Qian Shen Zhong-Chang Wang Song-Yu Wu Shen-Zhen Ren Ruo-Jun Man Bao-Zhong Wang Hai-Liang Zhu 《Bioorganic & medicinal chemistry letters》2017,27(16):3653-3660
In our previous study, we designed a series of pyrazole derivatives as novel COX-2 inhibitors. In order to obtain novel dual inhibitors of COX-2 and 5-LOX, herein we designed and synthesized 20 compounds by hybridizing pyrazole with substituted coumarin who was reported to exhibit 5-LOX inhibition to select potent compounds using adequate biological trials sequentially including selective inhibition of COX-2 and 5-LOX, anti-proliferation in vitro, cells apoptosis and cell cycle. Among them, the most potent compound 11g (IC50 = 0.23 ± 0.16 μM for COX-2, IC50 = 0.87 ± 0.07 μM for 5-LOX, IC50 = 4.48 ± 0.57 μM against A549) showed preliminary superiority compared with the positive controls Celecoxib (IC50 = 0.41 ± 0.28 μM for COX-2, IC50 = 7.68 ± 0.55 μM against A549) and Zileuton (IC50 = 1.35 ± 0.24 μM for 5-LOX). Further investigation confirmed that 11g could induce human non-small cell lung cancer A549 cells apoptosis and arrest the cell cycle at G2 phase in a dose-dependent manner. Our study might contribute to COX-2, 5-LOX dual inhibitors thus exploit promising novel cancer prevention agents. 相似文献
19.
Yali Wang Situ Xue Ruolan Li Zhihui Zheng Hong Yi Zhuorong Li 《Bioorganic & medicinal chemistry》2018,26(1):8-16
A series of chalcone derivatives bearing benzamide or benzenesulfonamide moieties were synthesized and evaluated for their anti-tumor effect on HCT116, MCF7 and 143B cell lines in vitro. SAR analysis showed that compounds bearing a benzenesulfonamide group had greater potency than those bearing a benzamide group. It was also shown that compounds with a mono-methyl or mono-halogen group at the 3-position on the terminal phenyl ring were more effective than those with trifluoromethyl or methoxy groups. Compound 8e exhibited the most potent anti-tumor activities against HCT116, MCF7 and 143B cell lines, with IC50 values of 0.597, 0.886 and 0.791 μM, respectively. Molecular docking studies and enzymatic assays demonstrated that the anti-tumor activity of compound 8e might be regulated by Cat L and Cat K. 相似文献
20.
Yong-Ling Wu De-Long Wang En-Hui Guo Shuang Song Jun-Tao Feng Xing Zhang 《Bioorganic & medicinal chemistry letters》2017,27(5):1284-1290
Thirty-six new α-benzylidene-γ-lactone compounds based α-methylene-γ-butyrolactone substructure were prepared and characterized by spectroscopic analysis. All compounds were evaluated for antifungal activities in vitro against six plant pathogenic fungi and the half maximal inhibitory concentration (IC50) against Botrytis cinerea and Colletotrichum lagenarium were investigated. Compounds 5c-3 and 5c-5 with the halogen atom exhibited excellent fungicidal activity against B. cinerea (IC50 = 22.91, 18.89 μM). The structure-activity relationships (SARs) analysis indicated that the derivatives with electron-withdrawing substituents at the meta- or para-positions improves the activity. Via the heuristic method, the generated quantitative structure-activity relationship (QSAR) model (R2 = 0.961) revealed a strong correlation of antifungal activity against B. cinerea with molecular structures of these compounds. Meanwhile, the cytotoxicity of 20 representative derivatives was tested in the human tumor cells line (HepG2) and the hepatic L02 cells line, the result indicated that the synthesized compounds showed significant inhibitory activity and limited selectivity. Compound 5c-5 has the highest fungicidal activity with IC50 = 18.89 μM (against B. cinerea.) but low cytotoxicity with IC50 = 35.4 μM (against HepG2 cell line) and IC50 = 68.8 μM (against Hepatic L02 cell line). These encouraging results can be providing an alternative, promising use of α-benzylidene-γ-lactone through the design and exploration of eco-friendly fungicides with low toxicity and high efficiency. 相似文献