共查询到20条相似文献,搜索用时 15 毫秒
1.
Bojan Burja Tamara Čimbora-Zovko Sanja Tomić Tihana Jelušić Marijan Kočevar Slovenko Polanc Maja Osmak 《Bioorganic & medicinal chemistry》2010,18(7):2375-2387
A series of pyrazolone-fused combretastatins and precursors were synthesized and their cytotoxicity as well as antitubulin potential was evaluated. The hydrazide 9f and the pyrazolone-fused combretastatins 12a, 12b and 12c were highly cytotoxic against various tumor cell lines including cisplatin resistant cells. The same compounds were also the best inhibitors of tubulin polymerization. Molecular modeling results showed that they bind the colchicine binding site at the tubulin heterodimer. The hydrazide 9f arrested HeLa cells in the G2/M phase of the cell cycle and strongly affected cell shape and microtubule network. 相似文献
2.
Borrel C Thoret S Cachet X Guénard D Tillequin F Koch M Michel S 《Bioorganic & medicinal chemistry》2005,13(11):3853-3864
Two series of combretastatin A4 derivatives (acrylamide=carboxamide and carbamate) were synthesized in order to improve the water solubility and stabilize the cis-configuration of the double bond. Their cytotoxic effects were evaluated against MCF-7, KB-3-1 and IGROV human cancer cell lines, as well as their inhibitory activity on tubulin polymerization. Results were compared to those of carboxamide 1, chosen as reference. Potent inhibitions were observed on both tests in the carboxamide series, particularly for compound 4d bearing a fluorine group in replacement of the 3-hydroxyl of CA4. In contrast, most of the carbamates were either inactive or displayed only moderate cytotoxicities. Interestingly, a submicromolar IC(50) was measured on MCF-7 cells for 6g, although this compound was totally devoid of antitubulin activity. 相似文献
3.
A number of analogues of combretastatin A-4 (1), containing a thiophene ring interposed between the two phenyl groups, have been prepared. The synthesis of these compounds employed a combination of palladium-mediated coupling and iodocyclization techniques. The thiophene compounds 11, 14, 18, and 19 also represent non-benzofused analogues of some recently described tubulin binding benzo[b]thiophenes 3-5. The most active thiophene compounds identified in this study were 11, 14, and 18. Overall they are less active than 1 but exhibit comparable activity to the most active of the benzo[b]thiophenes 3-5. A structure-activity relationship of these compounds is considered. 相似文献
4.
Dupont C Guénard D Tchertanov L Thoret S Guéritte F 《Bioorganic & medicinal chemistry》1999,7(12):3434-2969
Novel (-)- and (+)-rhazinilam derivatives substituted on the D-ring (compounds 3, 4, 5 and 6) have been prepared from (+)-vincadifformine 7 and (-)-tabersonine and evaluated against the disassembly of microtubules into tubulin. Along with this study, a reproducible 'one pot' semisynthesis of (-)-rhazinilam 1 from (+)-1,2-didehydroaspidospermidine 2 was performed allowing the easy preparation of these new compounds. 相似文献
5.
B del Rey A C Ramos E Caballero A Inchaustti G Yaluff M Medarde A Rojas de Arias A San Feliciano 《Bioorganic & medicinal chemistry letters》1999,9(18):2711-2714
We have investigated the in vitro leishmanicidal activity of representative members from series II-V of combretastatin analogues and heteroanalogues. Most of them exhibited different degrees of activity against various strains of Leishmania spp. The diaryl(heteroaryl)ethane system or the more complex fused heterocyclic stilbenoids, constitute useful skeletal bases to support some kind of antiparasitic activity. Particularly, the incorporation of 2-furyl substituents led to potent antileishmanial compounds, which have been selected for in vivo testing on murine models. 相似文献
6.
Maya AB del Rey B Lamamie de Clairac RP Caballero E Barasoain I Andreu JM Medarde M 《Bioorganic & medicinal chemistry letters》2000,10(22):2549-2551
The 3,4,5-trimethoxyphenyl and 3-hydroxy-4-methoxyphenyl rings of combretastatin A-4 are deemed optimal for its activity as antimitotic agent. The replacement of either one by a naphthalene ring results in compounds with a potency comparable to that of the parent compound. These results show that the naphthalene ring is a good surrogate for the 3,4,5-trimethoxyphenyl or the 3-hydroxy-4-methoxyphenyl rings of combretastatin A-4 and that neither of them is essential for the antitumor activity. 相似文献
7.
Lavrado J Paulo A Gut J Rosenthal PJ Moreira R 《Bioorganic & medicinal chemistry letters》2008,18(4):1378-1381
A series of cryptolepine derivatives has been synthesized through the incorporation of short basic side-chains in the C-11 position of the 10H-indolo[3,2-b]quinoline scaffold. Their antiplasmodial activity was evaluated in vitro against the chloroquine resistant Plasmodium falciparum W2 strain, showing IC(50) values between 22 and 184 nM, while their cytotoxicity was assessed using HUVEC cells, revealing three compounds with a selectivity ratio higher than 10. The most selective of these derivatives, 4d, with a selectivity ratio of 46, was also the least cytotoxic of the series. 相似文献
8.
A series of aryl- and aroyl-substituted chalcone analogues of the tubulin binding agent combretastatin A4 (1) were prepared, using a recently introduced one-pot palladium-mediated hydrostannylation-coupling reaction sequence. These chalcones were converted to indanones by Nazarov cyclisation, followed by oxidation to give the corresponding indenones. Indenones were also prepared using a palladium-mediated formal [3+2]-cycloaddition process between ortho-halobenzaldehydes and diarylpropynones. All compounds were assessed as inhibitors of tubulin polymerisation, but only E-31 had activity similar to that of 1. However, compound E-31 did not exhibit antiproliferative activity against the MCF-7 cell line. 相似文献
9.
N H Nam Y Kim Y J You D H Hong H M Kim B Z Ahn 《Bioorganic & medicinal chemistry letters》2001,11(23):3073-3076
Two series of combretoxazolones including 3,4-diaryloxazolones (6) and 4,5-diaryloxazolones (7) were synthesized and evaluated for cytotoxicity and antitumor activity. Both series showed strong cytotoxicities against a variety of tumor cell lines. Compound 6g exhibited a significant antitumor activity in BDF1 mice bearing B16 murine melanoma cells with inhibition rates of 67 and 61% at 100 and 30 mg/kg/day, respectively. 相似文献
10.
Lisowski V Enguehard C Lancelot J Caignard D Lambel S Leonce S Pierre A Atassi G Renard P Rault S 《Bioorganic & medicinal chemistry letters》2001,11(16):2205-2208
Structure-activity relationship studies of a new series of tripentones (thieno[2,3-b]pyrrolizin-8-ones), led us to prepare several derivatives with antiproliferative activities. The most promising 3-(3-hydroxy-4-methoxyphenyl)thieno[2,3-b]pyrrolizin-8-one 20 (leukemia L1210, IC(50)=15 nM) was shown to be a potent inhibitor of tubulin polymerization. 相似文献
11.
Burlingame MA Shaw SJ Sundermann KF Zhang D Petryka J Mendoza E Liu F Myles DC LaMarche MJ Hirose T Scott Freeze B Smith AB 《Bioorganic & medicinal chemistry letters》2004,14(9):2335-2338
A series of 7-deoxy discodermolide analogues in which the lactone fragment 'C' was replaced by aryl substituents were designed, synthesized, and evaluated for cytotoxicity. 相似文献
12.
《Journal of enzyme inhibition and medicinal chemistry》2013,28(2):180-194
We have synthesized a series of polymethoxylated rigid analogs of combretastatin A-4 which contain a benzoxepin ring in place of the usual ethylene bridge present in the natural combretastatin products. The compounds display antiproliferative activity when evaluated against the MCF-7 and MDA human breast carcinoma cell lines. 5-(3-Hydroxy-4-methoxyphenyl)-4-(3,4,5-trimethoxyphenyl)-2,3-dihydro-benzoxepine (11g) was found to be the most potent product when evaluated against the MCF-7 breast cancer cell line. A brief computational study of the structure–activity relationship for the synthesized compounds is presented. These 4,5-diarylbenzoxepins are identified as potentially useful scaffolds for the further development of antitumor agents which target tubulin. 相似文献
13.
A general strategy for the synthesis of 3'-prenylated chalcones was established and a series of prenylated hydroxychalcones, including the hop (Humulus lupulus L.) secondary metabolites xanthohumol (1), desmethylxanthohumol (2), xanthogalenol (3), and 4-methylxanthohumol (4) were synthesized. The influence of the A-ring hydroxylation pattern on the cytotoxic activity of the prenylated chalcones was investigated in a HeLa cell line and revealed that non-natural prenylated chalcones, like 2',3,4',5-tetrahydroxy-6'-methoxy-3'-prenylchalcone (9, IC(50) 3.2+/-0.4microM) as well as the phase 1 metabolite of xanthohumol (1), 3-hydroxyxanthohumol (8, IC(50) 2.5+/-0.5microM), were more active in comparison to 1 (IC(50) 9.4+/-1.4microM). A comparison of the cytotoxic activity of xanthohumol (1) and 3-hydroxyxanthohumol (8) with the non-prenylated analogs helichrysetin (12, IC(50) 5.2+/-0.8) and 3-hydroxyhelichrysetin (13, IC(50) 14.8+/-2.1) showed that the prenyl side chain at C-3' has an influence on the cytotoxicity against HeLa cells only for the dihydroxylated derivative. This offers interesting synthetic possibilities for the development of more potent compounds. The ORAC activity of the synthesized compounds was also investigated and revealed the highest activity for compounds 12, 4'-methylxanthohumol (4), and desmethylxanthohumol (2), with 4.4+/-0.6, 3.8+/-0.4, and 3.8+/-0.5 Trolox equivalents, respectively. 相似文献
14.
N-terminal analogues of cecropin A: synthesis, antibacterial activity, and conformational properties 总被引:5,自引:0,他引:5
Six analogues of the 37-residue antibacterial peptide cecropin A were synthesized by the solid-phase method: cecropin A-(2-37), [Glu2]cecropin A, [Pro4]cecropin A, [Glu6]cecropin A, [Leu6]cecropin A, and [Pro8]cecropin A. Their antibacterial activities against four test organisms were determined and related to conformational changes observed in their CD spectra and were discussed on the basis of a previously proposed amphipathic alpha-helix model. An aromatic residue in position 2 was shown to be important for activity against all tested bacteria. The highly alpha-helical 1-11 region of cecropin A did not appear to play a significant role in its activity against Escherichia coli but was clearly involved in its interaction against Pseudomonas aeruginosa, Bacillus megaterium, and Micrococcus luteus. 相似文献
15.
《Bioorganic & medicinal chemistry letters》2014,24(1):65-71
A new class of imine derivatives of hybrid chalcone analogues containing anthraquinone scaffold was synthesized and evaluated for their in vitro cytotoxic activity against HeLa, LS174, and A549 cancer cells. The compound 5n with furan ring linked to imino group showed potent activity against all target cells with IC50 values ranging from 1.76 to 6.11 μM. A mode of action study suggested that compounds induced changes typical for apoptosis in HeLa cells. The most active compounds inhibited tubulogenesis and 5h was found to exhibit a strong anti-angiogenic effect. 相似文献
16.
Urbaniak MD Frost LM Bingham JP Kelland LR Hartley JA Woolfson DN Caddick S 《Bioorganic & medicinal chemistry letters》2003,13(12):2025-2027
Compounds containing the naphthoate moiety of Neocarzinostatin chromophore or 2-hydroxynaphthoate have been synthesized and evaluated for cytotoxic activity against a leukemia cell line and a small panel of human-tumor cell lines. Those compounds containing a cyclopentenone moiety were active, with the carbonyl group being essential for biological activity. 相似文献
17.
Gwaltney SL Imade HM Barr KJ Li Q Gehrke L Credo RB Warner RB Lee JY Kovar P Wang J Nukkala MA Zielinski NA Frost D Ng SC Sham HL 《Bioorganic & medicinal chemistry letters》2001,11(7):871-874
Sulfonate analogues of combretastatin A-4 have been prepared. These compounds compete with colchicine and combretastatin A-4 for the colchicine binding site on tubulin and are potent inhibitors of tubulin polymerization and cell proliferation. Importantly, these compounds also inhibit the proliferation of P-glycoprotein positive (+) cancer cells, which are resistant to many other antitumor agents. 相似文献
18.
Three series (series A-C) of coumarin analogues with phenylpiperazine functions as substitution were designed and synthesized for studying their potential for treating Alzheimer's (AD) disease. Their anticholinesterase activities were assayed according to Ellmann's method against freshly prepared acetylcholinesterase (AChE) from Electrophorus electricus using donepezil as the reference compound. Pharmacological study and preliminary structure-activity relationships showed that coumarins with substitution on positions 3 and/or 4 have parallel anti-AchE activities compared with the reference compound. 相似文献
19.
Youssef D Nichols CE Cameron TS Balzarini J De Clercq E Jha A 《Bioorganic & medicinal chemistry letters》2007,17(20):5624-5629
A series of novel cyclic analogues of curcumin were synthesized and analyzed for in vitro cytostatic activity. Condensation of 2-acetylcycloalkanones with a variety of aromatic aldehydes resulted in the formation of 2-arylidene-6-(3-arylacryoyl)-cycloalkanone derivatives. A number of these analogues were found to have significant anticancer activity against representative murine and human cancer cell lines during in vitro bioassays. This corroborated with in vitro cytostatic activity against a panel of 60 cell lines studied at the National Cancer Institute (USA). 相似文献
20.
1,4-Piperazine and 4-hydroxyproline, two small cyclic polyfunctional systems with defined stereochemistry, were introduced as "molecular scaffolds." We define a "bioactive topology," which is a derived putative low-energy conformation obtained through theoretical conformational analysis of substance P. Substitution of these molecular scaffolds by pharmacophors characteristic of the bioactive topology of the C-terminal hexapeptide of substance P resulted in active, partially nonpeptidal substance P mimetic agonists. The study discusses the concepts and tools used to achieve this structural transformation, and points out the need to address flexibility-rigidity issues in an attempt to maintain sufficient molecular plasticity. 相似文献