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1.
Zhao M Bi L Wang W Wang C Baudy-Floc'h M Ju J Peng S 《Bioorganic & medicinal chemistry》2006,14(20):6998-7010
Beta-carboline represents a class of compounds with potent anti-tumor activity by intercalating with DNA. To further enhance the cytotoxic potency and bioavailability of beta-carboline, a series of novel beta-carboline amino acid ester conjugates were designed and synthesized, and the cytotoxic activities of these compounds were tested using a panel of human tumor cell lines. In addition, the membrane permeability of these compounds was evaluated in vitro using a Caco-2 cell monolayer model. The beta-carboline amino acid ester conjugates demonstrated improved cytotoxic activity compared to the parental beta-carbolines. In particular, the Lys/Arg conjugates were the most potent analogs with an IC(50) value of 4 and 1 microM against human cervical carcinoma cells. The low interaction energy of Arg conjugate based on molecular modeling may contribute to its enhanced cytotoxicity. Taken together, this study provided new insights into structure-activity relationships in the beta-carboline amino acid ester conjugates and identified the beta-carboline Lys/Arg conjugates as promising lead compounds for further in vivo biological and molecular evaluation. 相似文献
2.
A series of 3-substituted-beta-carboline derivatives was synthesized from L-tryptophan. The intercalating binding mode of these compounds with DNA, the effects of the flexible alkylamine side chain on the intercalating ability and their antitumor activity were studied, which agreed well with the molecular modeling results. 相似文献
3.
Dallavalle S Merlini L Beretta GL Tinelli S Zunino F 《Bioorganic & medicinal chemistry letters》2004,14(23):5757-5761
Luotonin A is a cytotoxic alkaloid that has been shown to inhibit topoisomerase I via stabilization of the binary complex topoisomerase-DNA in the same fashion as camptothecin. The synthesis and the cytotoxic activity on the lung carcinoma cell line H460 of a series of derivatives of Luotonin A is reported. The compounds inhibit topoisomerase I but show weak cytotoxic activity, thus confirming the peculiarity of ring E of camptothecin for antitumor activity. 相似文献
4.
Bazin MA Le Lamer AC Delcros JG Rouaud I Uriac P Boustie J Corbel JC Tomasi S 《Bioorganic & medicinal chemistry》2008,16(14):6860-6866
Nine usnic acid-amine conjugates were evaluated on murine and human cancer cell lines. The polyamine derivatives showed significant cytotoxicity in L1210 cells. Their activities appeared to be independent of the polyamine transport system (PTS). Indeed, their activities were similar in chinese hamster ovary (CHO) and in the PTS deficient CHO-MG cells. In addition, alpha-difluoromethylornithine, an ornithine decarboxylase inhibitor known to indirectly enhance the activity of the PTS and consequently increase the cytotoxicity of cytotoxic drugs entering cells via the PTS, had no effect on the activity of the polyamine derivatives. The more active derivative (1,8-diaminooctane derivative) displayed similar activities on all cancer cell lines studied and induced apoptosis. 相似文献
5.
S Serra A Chicca G Delogu S Vázquez-Rodríguez L Santana E Uriarte L Casu J Gertsch 《Bioorganic & medicinal chemistry letters》2012,22(18):5791-5794
Coumarins are a large family of natural and synthetic compounds exerting different pharmacological effects, including cytotoxic, anti-inflammatory or antimicrobial. In the present communication we report the synthesis of a series of 12 diversely substituted 4-oxycoumarin derivatives including methoxy substituted 4-hydroxycoumarins, methyl, methoxy or unsubstituted 3-aryl-4-hydroxycoumarins and 4-benzyloxycoumarins and their anti-proliferative effects on breast adenocarcinoma cells (MCF-7), human promyelocytic leukemia cells (HL-60), human histiocytic lymphoma cells (U937) and mouse neuroblastoma cells (Neuro2a). The most potent bioactive molecule was the 4-hydroxy-5,7-dimethoxycoumarin (compound 1) which showed similar potency (IC(50) 0.2-2μM) in all cancer cell lines tested. This non-natural product reveals a simple bioactive scaffold which may be exploited in further studies. 相似文献
6.
Shinji Tanimori Takeshi Nishimura Mitsunori Kirihata 《Bioorganic & medicinal chemistry letters》2009,19(15):4119-4121
Substituted dihydroquinozalin-2-ones (1–16) have been synthesized easily by the use of copper-catalyzed coupling method. The reactions of 2-haloanilines with a variety of α-amino acids in the presence of copper (I) iodide gave corresponding 3-substituted dihydroquinozalin-2-ones in up to 86% yield. Some new quinoxalin-2-ones (2, 4, 5, 13 and 16) have moderate cytotoxic activity toward HeLaS3 cell lines at 4.9–18.1 μM. 相似文献
7.
Seref Demirayak Rana Beis Ahmet C. Karaburun Ismail Kayagil Zerrin Incesu Umit Ucucu 《Journal of enzyme inhibition and medicinal chemistry》2013,28(1):113-118
Some 1,5-diaryl-3-ethoxycarbonyl-2-methylpyrrole derivatives were obtained by reacting 1-aryl-3-ethoxycarbonylpent-1,4-diones and a suitable aniline derivative or sulfanilamide under Paal-Knorr pyrrole synthesis conditions. The cytotoxicity of the compounds was tested and all compounds, except for compound 2 h, showed a time-dependent increase in cytotoxic activity. Analgesic activities of the compounds were determined by using the tail-flick and tail-immersion methods; some of the compounds showed potent analgesic activity. 相似文献
8.
Demirayak S Beis R Karaburun AC Kayagil I Incesu Z Ucucu U 《Journal of enzyme inhibition and medicinal chemistry》2006,21(1):113-118
Some 1,5-diaryl-3-ethoxycarbonyl-2-methylpyrrole derivatives were obtained by reacting 1-aryl-3-ethoxycarbonylpent-1,4-diones and a suitable aniline derivative or sulfanilamide under Paal-Knorr pyrrole synthesis conditions. The cytotoxicity of the compounds was tested and all compounds, except for compound 2 h, showed a time-dependent increase in cytotoxic activity. Analgesic activities of the compounds were determined by using the tail-flick and tail-immersion methods; some of the compounds showed potent analgesic activity. 相似文献
9.
Sangthong S Krusong K Ngamrojanavanich N Vilaivan T Puthong S Chandchawan S Muangsin N 《Bioorganic & medicinal chemistry letters》2011,21(16):4813-4818
6-Deoxyclitoriacetal (1) and a series of 11 further derivatives of it (2-12) were synthesized and evaluated for their cytotoxic and topoisomerase IIα inhibitory activities. Compounds bearing epoxide (2), morpholine (6) and benzylamine (10) moieties showed promising in vitro cytotoxic activities against four cancer cell lines, with IC50 values ranging from 0.38 to 0.73 μM. These three compounds also strongly inhibited topoisomerase II activity at 68.3-93.5% and showed a moderately high DNA intercalating property. 相似文献
10.
Tian-Yi Zhang Zhan-Kui Yu Xue-Jun Jin Ming-Yue Li Liang-Peng Sun Chang-Ji Zheng Hu-Ri Piao 《Bioorganic & medicinal chemistry letters》2018,28(9):1657-1662
Five series of dihydrotriazine derivatives containing chalcone (13a–i), phenoxy acetophenone (14a–b), benzyl benzene (15a–c), naphthoxyl acetophenone (16a–b) and benzyl naphthalene (17a–h) moieties were designed and synthesized. The antibacterial and antifungal activities of these compounds were evaluated against several strains of Gram-positive and Gram-negative bacteria, as well as a single fungus. Compound 17h was found to be the most potent of all of the compounds tested, with an MIC value of 0.5?μg/mL against several Gram-positive (Staphylococcus aureus 4220 and QRSA CCARM 3505) and Gram-negative (Escherichia coli 1924) strains of bacteria. However, this compound was inactive against Pseudomonas aeruginosa 2742 and Salmonella typhimurium 2421, indicating that its antibacterial spectrum is similar to those of the positive controls gatifloxacin and moxifloxacin. The cytotoxic activity of the compound 13i, 16b and 17h was assessed in Human normal liver cells. 相似文献
11.
Chung-Ren Su Sheau Farn Yeh Chih Miem Liu Amooru G. Damu Tsung-Hsiao Kuo Po-Cheng Chiang Kenneth F. Bastow Kuo-Hsiung Lee Tian-Shung Wu 《Bioorganic & medicinal chemistry》2009,17(16):6137-6143
Four natural pyranocoumarins clausenidin (1), nordentatin (2), clausarin (3), and xanthoxyletin (4) were isolated from the medicinal plant Clausena excavata. Recently, we found that 1 and 2 suppressed hepatitis B virus surface antigen in HepA2 cells, and in addition, 1–3 showed cytotoxic activity against four human cancer cell lines (A549, MCF7, KB, and KB-VIN). To explore the SAR of 1–4, 17 pyranocoumarin analogues (5–21) were designed and synthesized. Among these analogues, 5 and 10 were the most potent against hepatitis B virus with EC50 values of 1.14 and 1.34 μM, respectively. The most interesting result in the cytotoxicity assay was the significant activity of 1, 5, and 6 against the multi-drug resistant cell line, KB-VIN, without activity against the KB cell line. These data suggest that these three compounds could be useful hits for developing MDR-inverse drugs. 相似文献
12.
A series of substituted urea derivatives, compounds 1-14, were synthesized and evaluated for their cytotoxic activities against the human-leukemia K562 cell line. Two structurally simple compounds, 7 and 12, both incorporating a morpholine ring, were found to be highly active, with IC50 values of ca. 0.25 microM. 相似文献
13.
P. Sambasiva Rao C. Kurumurthy B. Veeraswamy G. Santhosh Kumar P. Shanthan Rao R. Pamanji J. Venkateswara Rao B. Narsaiah 《Bioorganic & medicinal chemistry letters》2013,23(5):1225-1227
The propargyl alcohol on reaction with alkylazides under Sharpless conditions through click chemistry concept gave exclusively 1,4-disubstituted triazoles 2. The compounds 2 were oxidized to aldehydes 3 followed by reaction with aniline resulted Schiff’s bases 4. The compounds 4 was further reacted with various aldehydes having α-hydrogen using molecular iodine as a catalyst and obtained 2-alkyl triazole-3-alkyl substituted quinoline derivatives 5. All the final compounds were screened against four human cancer cell lines (THP-1, Colo205, U937 & HeLa) and promising compounds have been identified. 相似文献
14.
Four new beta-carboline derivatives were synthesized bearing guanidinium group or amino group-terminated side chain targeting the TAR element. Compounds 5 and 6 with terminal guanidinium group showed inhibitory activities on Tat-TAR interaction as well as to HIV-1 in MT4 cells. Furthermore, capillary electrophoresis assay implied that compound 6 could not only bind to TAR but also hinder the Tat-TAR interaction. 相似文献
15.
Chen SW Wang YH Jin Y Tian X Zheng YT Luo DQ Tu YQ 《Bioorganic & medicinal chemistry letters》2007,17(7):2091-2095
In order to explore the range of biological activities of the podophyllotoxin compound class, a novel series of derivatives of podophyllotoxin, which were conjugates containing stavudine and different structural podophyllotoxin analogues, were designed, synthesized, and evaluated for their anti-HIV-1 activities in vitro. Among these compounds, 19d and 19c showed the highest anti-HIV-1 activities with EC(50) values of 0.17 and 0.29 microM and TI values of 466.9 and 354.5, respectively. 相似文献
16.
Radhakrishnan Surendra Kumar Meera Moydeen Salem S. Al-Deyab Aseer Manilal Akbar Idhayadhulla 《Bioorganic & medicinal chemistry letters》2017,27(1):66-71
A simple and convenient one-pot four-component synthesis of morpholine-connected pyrazolidine derivatives 2a–f and 4a–f was developed using direct metal-free catalysis, with the identities of the synthesized compounds confirmed by IR, NMR (1H and 13C), mass spectrometry, and elemental analysis. The prepared compounds were inspected for antimicrobial, antioxidant, and cytotoxic activities.Antimicrobial and antifungal activities against five bacterial and four fungal pathogens, respectively, were investigated using the disc diffusion technique. In antibacterial activity, compounds 2d and 2f (MIC = 2 μg/mL) exhibited significantly higher activity than the standard ciprofloxacin. The results of antifungal assay showed that the activity of compound 4a (MIC = 0.5 μg/mL) was significantly higher than the standard clotrimazole. Antioxidant activity was screened based on ABTS+ radical scavenging and linoleic acid peroxidation performance. Compound 4a showed substantial antioxidant (91.3%) activities, as compared with the Trolox standard. Cytotoxicity was evaluated using HepG2 (liver), HeLa (cervical), and MCF-7 (breast) cancer cell lines, with high toxicities observed for 2b (GI50 = 12.2 μm) and 4a (GI50 = 07.8 μm). 相似文献
17.
Chabane H Pierre A Leonce S Pfeiffer B Renard P Thiery V Guillaumet G Besson T 《Journal of enzyme inhibition and medicinal chemistry》2004,19(6):567-575
The synthesis and biological evaluation of some novel thiazolofluorenones, thiazolofluorenes and thiazoloanthraquinones, substituted with amino side-chains are described. These polyheterocyclic compounds have been synthesized via the corresponding imino-1,2,3-dithiazoles. Their cytotoxic activity and their eventual selective effect on a phase of the cell cycle were evaluated in vitro, using the murine lymphocytic L1210 leukaemia cell line. 相似文献
18.
Sun CM Lin LG Yu HJ Cheng CY Tsai YC Chu CW Din YH Chau YP Don MJ 《Bioorganic & medicinal chemistry letters》2007,17(4):1078-1081
A series of 4,5-diarylisoxazoles related to combretastatin A-4 (CA-4) were synthesized and evaluated for cytotoxicity against three human cancer cell lines. Among them, compound 6e showed better cytotoxic activity than CA-4 in HeLa and HepG2 cell lines assayed with IC(50) value as low as 0.022 and 0.065nM, respectively. 相似文献
19.
Tomoya Shiro Keisuke Kakiguchi Hirotada Takahashi Hidetaka Nagata Masanori Tobe 《Bioorganic & medicinal chemistry》2013,21(7):2068-2078
We have previously reported 7-bromo-2-(2-chrolophenyl)-imidazoquinolin-4(5H)-one (1) as a novel potent mPGES-1 inhibitor. To clarify the essential functional groups of 1 for inhibition of mPGES-1, we investigated this compound structure–activity relationship following substitution at the C(4)-position and N-alkylation at the N(1)-, the N(3)-, and the N(5)-positions of 1. To prepare the target compounds, we established a good methodology for selective N-alkylation of the imidazoquinolin-4-one, that is, selective alkylation of 1 at the N(3)- and N(5)-positions was achieved by use of an appropriate base and introduction of a protecting group at the nitrogen atom in the imidazole part, respectively. Replacement of the C(4)-oxo group with nitrogen- or sulfur- linked substituents gave decreased inhibitory activity for mPGES-1, and introduction of alkyl groups on the nitrogen atom at the N(1)-, the N(3)-, and the N(5)-positions resulted in even larger loss of inhibitory activity. These results revealed that the C(4)-oxo group, and the hydrogen atoms at the N(5)-position and the imidazole part were the best substituents. 相似文献
20.
Di Fabio R Giovannini R Bertani B Borriello M Bozzoli A Donati D Falchi A Ghirlanda D Leslie CP Pecunioso A Rumboldt G Spada S 《Bioorganic & medicinal chemistry letters》2006,16(6):1749-1752
The SAR of a new series of tetrahydrocarbazole derivatives is described: the appropriate decoration of this template led to the identification of a new class of NPY-1 antagonists showing good in vitro potency and a promising in vivo pharmacokinetic profile in rat. 相似文献