共查询到20条相似文献,搜索用时 0 毫秒
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Labruère R Gautier B Testud M Seguin J Lenoir C Desbène-Finck S Helissey P Garbay C Chabot GG Vidal M Giorgi-Renault S 《ChemMedChem》2010,5(12):2016-2025
We designed and synthesized two novel series of azapodophyllotoxin analogues as potential antivascular agents. A linker was inserted between the trimethoxyphenyl ring E and the tetracyclic ABCD moiety of the 4-aza-1,2-didehydropodophyllotoxins. In the first series, the linker enables free rotation between the two moieties; in the second series, conformational restriction of the E nucleus was considered. We have identified several new compounds with inhibitory activity toward tubulin polymerization similar to that of CA-4 and colchicine, while displaying low cytotoxic activity against normal and/or cancer cells. An aminologue and a methylenic analogue were shown to disrupt endothelial cell cords on Matrigel at subtoxic concentrations, and an original assay of drug washout allowed us to demonstrate the rapid reversibility of this effect. These two new analogues are promising leads for the development of vascular-disrupting agents in the podophyllotoxin series. 相似文献
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Dr. Dahong Li Dr. Shengtao Xu Hao Cai Lingling Pei Dr. Lei Wang Prof. Xiaoming Wu Prof. Hequan Yao Prof. Jieyun Jiang Yijun Sun Prof. Jinyi Xu 《ChemMedChem》2013,8(5):812-818
A library of promising enmein‐type 14‐O‐diterpenoid derivatives was constructed from a commercially available kaurene‐type oridonin by practical and efficient synthetic methods. These synthetic derivatives were evaluated for their antiproliferative activities against a set of four human cancer cell lines. The IC50 values are similar to or improved over those of the parent molecule and paclitaxel, the latter of which was used as a positive control. Compound 29 was further investigated for its apoptotic properties against human hepatocarcinoma Bel‐7402 cells to better understand its mode of action. Moreover, compound 29 was shown to have potent antitumor activity in vivo in studies with a murine model of gastric cancer (MGC‐803 mice). These results warrant further preclinical investigations of these diterpenoid‐based analogues as potential novel anticancer chemotherapeutics. 相似文献
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Claudia Pessoa Dr. Paulo Michel P. Ferreira Letícia Veras C. Lotufo Dr. Manoel O. de Moraes Prof. Suellen M. T. Cavalcanti Lucas Cunha D. Coêlho Marcelo Z. Hernandes Dr. Ana Cristina L. Leite Prof. Carlos A. De Simone Dr. Vlaudia M. A. Costa Dr. Valdênia M. O. Souza Dr. 《ChemMedChem》2010,5(4):486-486
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Aaron J. DeBono Jin Han Xie Dr. Sabatino Ventura Prof. Colin W. Pouton Dr. Ben Capuano Prof. Peter J. Scammells 《ChemMedChem》2012,7(12):2122-2133
Noscapine is a phthalideisoquinoline alkaloid isolated from the opium poppy Papaver somniferum. It has long been used as an antitussive agent, but has more recently been found to possess microtubule‐modulating properties and anticancer activity. Herein we report the synthesis and pharmacological evaluation of a series of 6′‐substituted noscapine derivatives. To underpin this structure–activity study, an efficient synthesis of N‐nornoscapine and its subsequent reduction to the cyclic ether derivative of N‐nornoscapine was developed. Reaction of the latter with a range of alkyl halides, acid chlorides, isocyanates, thioisocyanates, and chloroformate reagents resulted in the formation of the corresponding N‐alkyl, N‐acyl, N‐carbamoyl, N‐thiocarbamoyl, and N‐carbamate derivatives, respectively. The ability of these compounds to inhibit cell proliferation was assessed in cell‐cycle cytotoxicity assays using prostate cancer (PC3), breast cancer (MCF‐7), and colon cancer (Caco‐2) cell lines. Compounds that showed activity in the cell‐cycle assay were further evaluated in cell viability assays using PC3 and MCF‐7 cells. 相似文献
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Montakarn Chittchang Dr. Paratchata Batsomboon Somsak Ruchirawat Prof. Dr. Poonsakdi Ploypradith Dr. 《ChemMedChem》2009,4(3):298-298
The inside cover picture shows the structure of lamellarin N as a representative of cytotoxic marine lamellarin alkaloids, together with a potential molecular target, the topoisomerase I–DNA complex. Systematic SAR studies revealed the importance of the substituents for potent cytotoxicity. For more details, see the Full Paper by P. Ploypradith et al. on p. 457 ff.
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Dr. Ahmed Kamal Vangala Santhosh Reddy Santosh Karnewar Sumit S. Chourasiya Anver Basha Shaik G. Bharath Kumar Chandan Kishor M. Kashi Reddy M. P. Narasimha Rao Dr. Ananthamurthy Nagabhushana Kallaganti V. S. Ramakrishna Dr. Anthony Addlagatta Dr. Srigiridhar Kotamraju 《ChemMedChem》2013,8(12):2080-2080
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Inside Cover: Targeted Delivery of Proteasome Inhibitors to Somatostatin‐Receptor‐Expressing Cancer Cells by Octreotide Conjugation (ChemMedChem 12/2015) 下载免费PDF全文
Dr. Philipp Beck Haissi Cui Dr. Julian D. Hegemann Prof. Dr. Mohammed A. Marahiel Prof. Dr. Achim Krüger Prof. Dr. Michael Groll 《ChemMedChem》2015,10(12):1942-1942
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Miriam Martins Alho Dr. Rory N. García‐Sánchez Juan José Nogal‐Ruiz Dr. José Antonio Escario Dr. Alicia Gómez‐Barrio Dr. Antonio R. Martínez‐Fernández Dr. Vicente J. Arán Dr. 《ChemMedChem》2009,4(1):78-87
Bis(indazol‐3‐ol) derivatives ( 5 , 30–38 ) were prepared by alkylation of 3‐alkoxyindazoles with α,ω‐dibromides, followed by removal of the O‐protecting groups. These compounds were subsequently evaluated as inhibitors of biocrystallization of ferriprotoporphyrin IX (heme) to hemozoin, a Plasmodium detoxification specific process. Most bis(5‐nitroindazol‐3‐ols) were good inhibitors, however, a denitro analogue ( 38 ), the intermediate bis(3‐alkoxyindazoles) ( 15 – 29 ) as well as bis(indazolin‐3‐ones) ( 39 – 42 ) were not active, showing the importance of the NO2 and OH groups in the inhibition process. 相似文献
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Design,Synthesis, and Biological Evaluation of Shikonin and Alkannin Derivatives as Potential Anticancer Agents via a Prodrug Approach 下载免费PDF全文
Dr. Ru‐Bing Wang Dr. Wen Zhou Dr. Qing‐Qing Meng Dr. Xu Zhang Jing Ding Yan Xu Hua‐Long Song Dr. Kai Yang Dr. Jia‐Hua Cui Prof. Shao‐Shun Li 《ChemMedChem》2014,9(12):2798-2808
To minimize the cytotoxicity of shikonin and alkannin that arises through the generation of reactive oxygen species (ROS) and alkylation of the naphthazarin ring, two series of novel core‐scaffold‐modified shikonin and alkannin derivatives were designed. These derivatives, which differ in their configurational and positional isomerism (R‐, S‐, and 2‐ and 6‐isomers) were synthesized in high enantiomeric excess (>99 % ee). The selectivity of the dimethylated derivatives was significantly higher than the parent shikonin in vitro, but some side effects were still observed in vivo. Surprisingly, the dimethylated diacetyl derivatives with poor anticancer activity in vitro showed tumor‐inhibiting effects similar to paclitaxel without any toxicity in vivo. The anticancer activity of these derivatives is in agreement with their low ROS generation and alkylating capacity, emphasizing their potential as prodrugs. This strategy provides means to address the nonspecific cytotoxicity of naphthazarin analogues toward normal cells. 相似文献
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Dr. Jianmei Cui Dr. Jinshan Jin Dr. Ying‐Hsin Hsieh Dr. Hsiuchin Yang Dr. Bowen Ke Dr. Krishna Damera Dr. Phang C. Tai Dr. Binghe Wang 《ChemMedChem》2013,8(8):1384-1393
SecA, a key component of bacterial Sec‐dependent secretion pathway, is an attractive target for exploring novel antimicrobials. Rose bengal (RB), a polyhalogenated fluorescein derivative, was found from our previous study as a potent SecA inhibitor. Here we describe the synthesis and structure–activity relationships (SAR) of 23 RB analogues that were designed by systematical dissection of RB. Evaluation of these analogues allowed us to establish an initial SAR in SecA inhibition. The antimicrobial effects of these SecA inhibitors are confirmed in experiments using E. coli and B. subtilis. 相似文献
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Abdallah Hamze Dr. Anne Giraud Dr. Samir Messaoudi Dr. Olivier Provot Dr. Jean‐François Peyrat Prof. Jérôme Bignon Dr. Jian‐Miao Liu Dr. Joanna Wdzieczak‐Bakala Dr. Sylviane Thoret Joëlle Dubois Dr. Jean‐Daniel Brion Prof. Mouad Alami Dr. 《ChemMedChem》2009,4(11):1912-1924
The cytotoxic activities of 23 new isocombretastatin A derivatives with modifications on the B‐ring were investigated. Several compounds exhibited excellent antiproliferative activity at nanomolar concentrations against a panel of human cancer cell lines. Compounds isoFCA‐4 ( 2 e ), isoCA‐4 ( 2 k ) and isoNH2CA‐4 ( 2 s ) were the most cytotoxic, and strongly inhibited tubulin polymerization with IC50 values of 4, 2 and 1.5 μM , respectively. These derivatives were found to be 10‐fold more active than phenstatin and colchicine with respect to growth inhibition but displayed similar activities as tubulin polymerization inhibitors. In addition, cell cycle arrest in the G2/M phase and subsequent apoptosis was observed in three cancer cell lines when treated with these compounds. The disruptive effect of 2 e , 2 k and 2 s on the vessel‐like structures formed by human umbilical vein endothelial cells (HUVEC) suggest that these compounds may act as vascular disrupting agents. Both compounds 2 k and 2 s have the potential for further prodrug modification and development as vascular disrupting agents for treatment of solid tumors. 相似文献