共查询到20条相似文献,搜索用时 15 毫秒
1.
Synthesis and antitumor activity of spergualin analogues. I. Chemical modification of 7-guanidino-3-hydroxyacyl moiety 总被引:3,自引:0,他引:3
Y Umeda M Moriguchi H Kuroda T Nakamura H Iinuma T Takeuchi H Umezawa 《The Journal of antibiotics》1985,38(7):886-898
Many analogues and derivatives of an antitumor antibiotic, spergualin, were synthesized, and the relationships between the structure and the activity against mouse L-1210 tumor were studied. Both modification of the 15-hydroxyl group and alteration of chain-length of the omega-guanidinoacyl moiety affected the activity. 15-Deoxyspergualin (18, 1-amino-19-guanidino-11-hydroxy-4,9,12-triazanonadecane-10,13-d ion e) and its analogue 25 (1-amino-21-guanidino-11-hydroxy-4,9,12-triazauneicosane-10,13-dio ne) had strong activity, superior to that of spergualin. 相似文献
2.
Immunosuppressive activity of 15-deoxyspergualin and its effect on skin allografts in rats 总被引:2,自引:0,他引:2
T Masuda S Mizutani M Iijima H Odai H Suda M Ishizuka T Takeuchi H Umezawa 《The Journal of antibiotics》1987,40(11):1612-1618
The immunosuppressive activity of spergualin analogues, 15-deoxyspergualin and N-30, is presented. These compounds suppressed antibody formation and establishment of delayed-type hypersensitivity to sheep red blood cells (SRBC) in mice. Among spergualin, 15-deoxyspergualin, and N-30, 15-deoxyspergualin was most effective in suppressing immune responses. It suppressed antibody formation against SRBC by spleen cell cultures in a dose-dependent fashion without reducing cell viability. The spergualins also suppressed the mixed lymphocyte culture reaction. Peritoneal exudate cells taken from mice given immunosuppressive doses of 15-deoxyspergualin were not reduced in their functions measured: Release of lysosomal enzymes and production of superoxide anions. 15-Deoxyspergualin and N-30 were markedly effective in prolonging skin graft in rats. 相似文献
3.
The method for chemical modification of spergualin with retention of the configuration at the C-11 has been achieved by the use of tetrahydropyranyl group for protection of the 11-hydroxyl group. (-)-15-Deoxyspergualin (2), which shows about eight times stronger inhibition against mouse leukemia L-1210 than the natural (-)-spergualin(1), and (-)-spergualin-15-phosphate(3) possessing a good antitumor activity have been synthesized starting from 1. 相似文献
4.
M Yamato K Hashigaki S Ishikawa N Kokubu Y Inoue T Tsuruo T Tashiro 《Journal of medicinal chemistry》1985,28(8):1026-1031
Structural requirement for antitumor activity of tropolone derivatives 2-4 was explored. Isochroman derivatives (6-17, 20, and 23) and alpha, alpha-disubstituted compounds 26-30 were synthesized and their antitumor activities were tested. These nontroponoid derivatives were all inactive, implying that a tropolone ring is essential for the activity. Several compounds related to the monotropolone analogue 3 were synthesized. Among them, 31-33 showed significant activity, but their potencies were considerably weaker than those of binary tropolone analogues 4. 相似文献
5.
G Cristalli P Franchetti M Grifantini S Vittori G Lupidi F Riva T Bordoni C Geroni M A Verini 《Journal of medicinal chemistry》1988,31(2):390-393
Two new deaza analogues of erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA, 1), 7-deaza-EHNA (6) and 1,3-dideaza-EHNA (11), were synthesized and evaluated for adenosine deaminase (ADA) inhibitory activity and compared with EHNA, 1-deaza-EHNA (2), and 3-deaza-EHNA (3). Substitution of a methine group for a nitrogen atom in the 7-position of the purine moiety of EHNA produces a dramatic drop in the inhibitory activity (Ki = 4 X 10(-4) M) whereas compounds 2 and 3 are still good inhibitors (Ki = 1.2 X 10(-7) M and 6.3 X 10(-9) M respectively). EHNA and its deaza analogues so far synthesized were also tested in vitro for their antiviral and antitumor activity in a range of cellular systems. EHNA and 1-deaza-EHNA are equiactive as inhibitors of human respiratory syncytial virus (HRSV) replication (MIC = 6.25 micrograms/mL) while the other compounds are inactive. On the other hand, all the examined compounds displayed an antitumor activity comparable to that of the reference compound 1-beta-D-arabinofuranosyladenine (ara-A), 7-deaza-EHNA being the most active of all. The results obtained showed that there is no correlation between adenosine deaminase inhibition and antiviral or antitumor activity in this series of compounds. 3-Deaza-EHNA, the most active inhibitor of ADA among the EHNA deaza analogues, greatly potentiates the antitumor activity of ara-A in vitro. In vivo activity was observed only when the two compounds were used in combination. 相似文献
6.
Chao Zheng Ming-Zong Li Wei-Ping Tang Li-Guang Lou 《Journal of Asian natural products research》2019,21(1):51-61
A series of E-ring lactone-opened camptothecin (CPT) derivatives bearing with terminal aza-heterocyclic groups were synthesized, and their antitumor activity was evaluated both in vitro and in vivo. Hydroxyl-amide analogues with morpholin-4-yl displayed excellent antitumor activity in vitro and efficient inhibition on tumor xenograph model in nude mice. Ester-amide compounds acted less active in vitro cytotoxicity and lower inhibition activity in vivo. Substitutions at 7- and 10- positions favored the antitumor activity. 相似文献
7.
Halogenated 4-(3,3-dimethyl-1-triazeno)quinolines were synthesized as potential antitumor agents on the basis of the biochemical pharmacological properties of existing triazenes, their structural-activity relationships, and the high melanin binding of chloroquine and iodoquine in vivo and in vitro. They were synthesized by diazotization of appropriate halogen-substituted 4-aminoquinolines in fluoboric acid at -5 degrees C followed by coupling with dimethylamine. Among these new compounds, 8-chloro-4-(3,3-dimethyl-1-triazeno)quinoline produces significant antitumor activity against both P-388 and L1210 murine leukemias. Although only marginally active or inactive against P-388, the other chloro, bromo, or iodo analogues show activity against L1210 comparable to that of dacarbazine (DIC). However, none of these compounds is active against B-16 melanoma. Compared with DIC these new agents demonstrate a higher in vitro affinity for melanin; however, this affinity is apparently not correlated with their antitumor activity. 相似文献
8.
Y Umeda M Moriguchi H Kuroda T Nakamura A Fujii H Iinuma T Takeuchi H Umezawa 《The Journal of antibiotics》1987,40(9):1303-1315
Chemical modifications of the spermidine moiety of an antitumor antibiotic, spergualin (Ia), and the structure-activity relationship are described. Replacement of spermidine with other polyamines decreased the antitumor activity against mouse leukemia L1210. Analogues containing an oxidized spermidine moiety that probably formed during oxidation with amine oxidase were inactive. Spermidine is indispensable for the antitumor activity. A facile method for the synthesis of glyoxyloyl polyamine, a key intermediate of spergualin-related compounds, is also reported. 相似文献
9.
Novel beta-hydroxy propenamides as analogues of the active metabolite of leflunomide (A 771726) were synthesized and evaluated for their inhibitory activity on dihydroorotate dehydrogenase (DHODH) in an investigation into their immunosuppressive activity. Compounds 2a, 3a, and 3h were approximately 4-40 times more potent than leflunomide in their activity while they were-less active than A 771726. 相似文献
10.
Analogues of penclomedine (PEN, 3,5-dichloro-4,6-dimethoxy-2-(trichloromethyl)pyridine) and its metabolites have been synthesized and evaluated as potential antitumor agents. PEN and 4-DMPEN (3,5-dichloro-4-hydroxy-6-methoxy2-(trichloromethyl)pyridine (3a)), the major plasma metabolite in patients, were modified at 4- and 6-positions with different alkyl, aryl, and ester groups. All of the analogues and many of the intermediates were evaluated against the PEN-sensitive MX-1 human breast tumor xenograft in vivo, and several analogues of PEN and 4-DMPEN showed modest to curative activity. 相似文献
11.
In an effort to increase of the antitumor activity of 2(S)-5,2',5'-trihydroxy-7,8-dimethoxyflavanone isolated fromScutellaria indica, we synthesized its analogues,II, III, andIV. They showed potent cytotoxicityin vitro against cancer cell lines, L1210, K562 and A549. On the basis of ED(50) values against the cancer cell lines,III exhibited about 2-7 times stronger activity thanI against various cell lines. We tested the antitumor activity of the analogues against Sarcoma 180 cellsin vivo and evaluated the structure-activity relationship. The antitumor activity appeared to be related to the hydrogen bond between carbonyl group at C-4 and hydroxyl group at C-5, in contrast to cytotoxic action. 相似文献
12.
Nine analogues of natural lignan justicidin A were easily synthesized employing Williamson etherification in yields of 76–84%.
Compounds were evaluated for their cytotoxic activities against hepatocellular carcinoma (HepG2) cell line using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium
bromide (MTT) assay. All synthesized analogues showed better antitumor activity than etoposide. 相似文献
13.
14.
1,2-bis(arylsulfonyl)hydrazines. 2. The influence of arylsulfonyl and aralkylsulfonyl substituents on antitumor and alkylating activity 总被引:1,自引:0,他引:1
K Shyam R Furubayashi R T Hrubiec L A Cosby A C Sartorelli 《Journal of medicinal chemistry》1986,29(7):1323-1325
Several 1,2-bis(arylsulfonyl)-1-methylhydrazines were synthesized and evaluated for antineoplastic activity against the L1210 leukemia. The most active compound to emerge from this study, 2-[(4-chlorophenyl)sulfonyl]-1-methyl-1-(4-tolylsulfonyl)hydrazine , increased the survival time of tumor-bearing mice by 88%. The alkylating activity of the synthesized analogues and several compounds reported earlier was determined by measuring the absorbance at 540 nm of the alkylated product of 4-(4-nitrobenzyl)pyridine. The results obtained support the concept that the ability to alkylate is a necessary but not a sufficient condition for the expression of antitumor activity by agents of this class. 相似文献
15.
4-酰硫基-4-脱氧-4-去甲表鬼臼毒素衍生物的合成和抗肿瘤活性 总被引:5,自引:0,他引:5
为研究4’-去甲表鬼臼毒素的C4位不同原子及不同取代基类型同活性之间的关系,寻找活性高、毒性低的抗肿瘤新药,合成了11个4-酰硫基-4-脱氧-4’-去甲表鬼臼毒素,衍生物并进行了抗肿瘤活性试验。4-巯基-4-脱氧-4’-去甲表鬼臼毒素和不同的羧酸在二乙氧基磷酰氰酯存在下得相应的硫酯。该类化合物在L1210白血病细胞和KB细胞的体外抑制试验中普遍表现出抑制活性。化合物10的活性与依托泊甙相当。其余活性比依托泊甙差。与相应的C4位酰氨基的4’-去甲表鬼臼毒素衍生物相比,活性明显弱。提示氮取代的衍生物活性更好。 相似文献
16.
Conti P Roda G Stabile H Vanoni MA Curti B De Amici M 《Il Farmaco; edizione pratica》2003,58(9):683-690
A set of racemic conformationally constrained analogues of the antitumor antibiotic acivicin (+)-1 has been prepared through a strategy based on 1,3-dipolar cycloaddition of bromonitrile oxide to suitable dipolarophiles. The bromo analogue (2) of acivicin was also synthesized and tested as a reference compound, together with its stereoisomer 3. The antitumor properties of novel amino acids 4-7 were evaluated in vitro against human tumor cell lines. Their efficacy to inhibit glutamate synthase (GltS) from Azospirillum brasilense was also assayed. None of the studied compounds, but 2, showed significant activity. 相似文献
17.
Several 5,8-bis[(aminoalkyl)amino]-1-azaanthracene-9,10-diones have been synthesized and evaluated for antitumor activity against L1210 leukemia both in vitro and in vivo. Comparisons are made to the corresponding carbocyclic analogues. One of the aza analogues showed modest in vivo activity. 相似文献
18.
19.
N Amishiro A Okamoto C Murakata T Tamaoki M Okabe H Saito 《Journal of medicinal chemistry》1999,42(15):2946-2960
A series of 3-substituted A-ring pyrrole compounds of duocarmycin were synthesized and evaluated for in vitro anticellular activity against HeLa S(3) cells and in vivo antitumor activity against murine sarcoma 180 in mice. These compounds were evaluated on the peripheral blood toxicity and delayed lethal toxicity. Further, to expand our investigation of their peripheral blood toxicity, the toxicity to bone marrow cells (CFU-GM, CFU-Meg) was investigated. Among 3-substituted A-ring pyrrole compounds of duocarmycin bearing a 5',6',7'-trimethoxy-2'-indolecarboxyl group as segment-B (Seg-B), several analogues showed remarkably potent antitumor activity with low peripheral blood toxicity. The 3-formyl compound 12h, one of such analogues, showed stronger antitumor activity with lower toxicity to bone marrow cells compared to DU-86 (2a), an active metabolite of KW-2189 (2b). However, compound 12h caused delayed death. On the other hand, the 3-bromo compound 15f, one of the 3-substituted A-ring pyrrole derivatives bearing a 4'-methoxycinnamoyl group as Seg-B, showed the most potent antitumor activity among the 4'-methoxycinnamate analogues with low toxicity to bone marrow cells. Furthermore, compound 15f did not cause delayed death similarly to 2d. These results would indicate the importance of the C-3 substituents of A-ring pyrrole duocarmycin derivatives for exhibiting antitumor activity and decreasing toxicity. 相似文献