硝基糠醛缩氨基硫脲衍生物的合成与抑菌活性

本文设计合成了１６种糠醛缩氨基硫脲衍生物，并对所合成的化合物进行了抑菌活性实验．结果表明：多种化合物对受试细菌有不同程度的抑制作用，有些化合物抑菌活性很高，很有发展前景。     

5—氯水杨醛类缩氨基硫脲的合成和抑菌活性研究

设计合成了三种５－氯水杨醛的缩氨基硫脲衍生物，经元素分析，红外光谱确定了其结构，并对化合物的抑菌活性进行了测试。     

呋喃甲醛缩氨基硫脲与Cu(Ⅰ)、Sn(Ⅱ)配合物的合成及抑菌活性

本文报道了2—呋喃甲醛缩氨基硫脲(L_1)、N~4—(对甲苯基)—2—呋喃甲醛缩氨基硫脲(L_2)及4个Cu(1)、Sn(1)配合物的合成。并进行了抑菌活性实验。     

抑菌剂N~4—对甲苯基苯甲醛缩氨硫脲的合成

<正> 缩氨基硫脲是一类具有广泛性生物活性的化合物,它具有抗细菌、抗真菌、抗肿瘤、抗病毒等活性。为了寻找高效、低毒的杀菌药物,我们合成了N~4—对甲苯基苯甲酸缩氨基硫脲,通过元素分析,红外光谱对其结构进行了确证,并对其抑菌活性进行初步     

苄胺衍生物与过渡金属离子Co（Ⅱ）和Ni（Ⅱ）配合物的研究

设计合成了四种以苄胺的缩氨基硫脲为配体的Ｃｏ（Ⅱ）和Ｎｉ（Ⅲ）配合物，经元素分析、红外光谱确证其结构，并对两种配合物的抑菌活性进行测试，结果表明，四种配合物对所试细菌都有不同程度的抑菌作用。     

Cu~(2+)与Ni~(2+)的缩氨基硫脲类配合物的合成

合成了以缩氨基硫脲衍生物为配体的4种Cu~(2+)和Ni~(2+)的配合物，通过元素分析、红外光谱确证了其结构组成，并对Cu~(2+)配合物和Ni~(2+)配合物的抑菌活性进行了测定。     

2-甲酰(乙酰)取代喹啉缩氨基硫脲的合成

缩氨基硫脲类化合物有抗肿瘤、抗病毒和抗菌等多种药理活性。Barret等首次报道了乙二醛二缩氨基硫脲(Ⅰ)的抗疟活性。Klayman等研究了缩     

糖类缩氨基硫脲衍生物及其过渡金属配合物的合成和生物活性的研究

缩氨基硫脲衍生物及其金属配合物具有抗肿瘤、抗病毒、抗真菌及抗细菌活性。但这类化合物却很少应用于临床,原因之一是其水溶性很小。因此,我们设计在这类化合物中引入了一个或多个亲水性基团。本研究合成了9种糖类缩氨基硫脲衍生物及它们的5种过渡金属配合物。其中,1种糖衍生物及其     

苯二醛缩氨基硫脲的合成及其酪氨酸酶抑制活性研究

目的 合成苯二醛单缩和二缩氨基硫脲类化合物,并初步研究其抑制酪氨酸酶的活性和作用机制。方法 以5种苯二醛和氨基硫脲为原料,通过缩合反应合成9个目标化合物;采用蘑菇酪氨酸酶多巴速率氧化法和酶抑制动力学实验,测定目标化合物对酪氨酸酶的抑制活性和作用机制;选择化合物3a和4a进行抑制机制和抑制动力学研究。结果 目标化合物的结构经¹H-NMR、¹³C-NMR及MS确证;所有化合物抑制酪氨酸酶的活性均优于对照药物曲酸;苯二醛二缩氨基硫脲3a~3d的活性明显强于相应的单缩氨基硫脲4a~4d;化合物3a和4a对酪氨酸酶的抑制作用均表现为混合型可逆抑制作用。结论 苯二醛二缩氨基硫脲类化合物具有优异的抑制酪氨酸酶的活性,值得进一步深入研究。     

若干呋喃西林类金属络合物的抑菌活性

报道了若干呋喃西林类金属络合物的抑菌活性,数据表明:羰基氧原子换成硫后可使化合物活性所提高。它们与铜(Ⅱ)、锌(Ⅱ)、钴(Ⅱ)、镍(Ⅱ)等形成络合物后可使抑菌活性发生显著变化。     

2-呋喃硫羰基腙衍生物及其过渡金属配位化合物的合成和抑菌活性

本文设计合成了九个2-呋喃硫羰基腙衍生物及其十三个不同的过渡金属配位化合物,并进行了抑菌实验,表明化合物对受试各种细菌均具有不同程度的抑菌作用。与2-呋喃硫羰基踪衍生物相比,配位化合物的抑菌活性发生显著的改变。其中,铜(Ⅱ)、镍(Ⅱ)、锌(Ⅱ)和银(Ⅰ)等配位化合物的活性较强,其它过渡金属配位化合物的活性较低。多数化合物对革兰氏阳性细菌的敏感性大于对革兰氏阴性细菌。     

The cytotoxicity of symmetrical and unsymmetrical bis(thiosemicarbazones) and their metal complexes in murine and human tumor cells

A number of thiosemicarbazones have been tested previously and herein are included three bis(thiosemicarbazones) for comparison to the previous derivatives. In general the uncomplexed thiosemicarbazones were more potent in the cytotoxic screens than the bis(thiosemicarbazone) except in the murine L1210 and the human colon SW480 screens. Mode of action studies have only demonstrated slight differences in the effects of the two types of compounds on nucleic acid metabolism. The symmetrical and unsymmetrical bis(thiosemicarbazones) complexes of copper, nickel, zinc, and cadmium have been examined to compare them to the heterocyclic N(4)-substituted thiosemicarbazones metal complexes. These new derivatives demonstrated excellent activity against the growth of suspended lymphomas and leukemias although it should be pointed out that generally they were not as active as the copper complexes of N(4)-substituted thiosemicarbazones. Nevertheless, selected bis(thiosemicarbazones) complexes were active against the growth of human lung MB9812, KB nasopharynx, epidermoid A431, glioma UM-86, colon SW480, ovary 1-A9, breast MCK-7, and osteosarcoma Saos-2. In human HL-60 promyelocytic leukemia cells the complexes preferentially inhibited DNA and purine syntheses over 60 min. The regulatory enzyme of the de novo purine pathway, IMP dehydrogenase, appeared to be a major target of the complexes. However, minor inhibition of the activities of DNA polymerase alpha, PRPP-amido transferase, ribonucleotide reductase, and nucleoside kinases occurred over the same time period. No doubt these effects of the complexes on nucleic acid metabolism were additive since the d[NTP] pool levels were reduced after 60 min as was DNA synthesis. The symmetrical and unsymmetrical bis(thiosemicarbazones) and their metal complexes did not cause as severe DNA fragmentation as the heterocyclic N(4)-substituted thiosemicarbazone metal complexes; furthermore, their metabolic effects in the tumor cell were more focused on a single synthetic pathway.     

Identification and characterization of thiosemicarbazones with antifungal and antitumor effects: cellular iron chelation mediating cytotoxic activity

Thiosemicarbazones derived from acetylpyrazines were prepared by condensing an acetylpyrazine or a ring-substituted acetylpyrazine with thiosemicarbazide. Using the same procedure, N, N-dimethylthiosemicarbazones were synthesized from acetylpyrazines and N, N-dimethylthiosemicarbazide. A total of 20 compounds (16 novel) were chemically characterized and then tested for antifungal effects on eight strains of fungi and also for antitumor activity against SK-N-MC neuroepithelioma cells. The most effective compound identified in terms of both antifungal and antitumor activity was N, N-dimethyl-2-(1-pyrazin-2-ylethylidene)hydrazinecarbothioamide (5a). The mechanism of action of this and its related thiosemicarbazones was due, at least in part, to its ability to act as a tridentate ligand that binds metal ions. This was deduced from preparation of the related thiosemicarbazones [acetophenone thiosemicarbazone (6) and acetophenone N, N-dimethylthiosemicarbazone (7)] that do not possess a coordinating ring-N, which plays a vital role in metal ion chelation. Furthermore, 5a and several other thiosemicarbazones that showed high antiproliferative activity were demonstrated to have marked iron (Fe) chelation efficacy. In fact, these agents were highly effective at mobilizing (59)Fe from prelabeled SK-N-MC cells and preventing (59)Fe uptake from the serum Fe transport protein, transferrin. In contrast, compounds 6 and 7 that do not possess a tridentate metal-binding site showed little activity. Further studies examining ascorbate oxidation demonstrated that the Fe complexes of the most effective compounds were redox-inactive. Thus, in contrast to other thiosemicarbazones with potent antiproliferative activity, Fe chelation and mobilization rather than free radical generation played a significant role in the cytotoxic effects of the current ligands.     

稀土盐及其配合物对芽孢菌的抑菌活性的影响

目的 以稀土氧化物为原料，合成系列稀土盐及其配合物，并研究它们对芽孢菌的抑菌作用规律。方法 采用了滤纸片法、稀释法考察了多种稀土盐及其配合物对多种芽孢菌、普通革兰氏阳性细菌及普通革兰氏阴性细菌的抑菌活性；并用透射电镜观察了芽孢的形态及超微结构变化。结果 稀土盐类及其配合物抑菌性强、抑菌谱广，对生命力强的芽孢菌显示了比对普通革兰氏阳性及阴性细菌更好的强抑菌效果；稀土配合物的抑菌效果较稀土盐更好；各种稀土盐类及其配合物对多种芽孢菌的抑菌活性差别不大；重稀土（Gd）抑菌效果略优于轻稀土(La,Nd,Eu）；不同配体合成的配合物对同一菌株的抑菌效果存在显著差异，这是由于抑菌活性与配合物的稳定性有关；采用透射电镜的负染色及超薄切片术，观测到稀土配合物对芽孢休眠体有直接的溶菌作用。结论 稀土配合物是一类对芽孢菌有特效的抑菌剂。     

2-Acetylpyridine thiosemicarbazones. 2. N4,N4-Disubstituted derivatives as potential antimalarial agents.

The most effective antimalarial agents among the N4-monosubstituted 2-acetylpyridine thiosemicarbazones recently described by us have a cyclohexyl or a phenyl substituent and produce cures in Plasmodium berghei infected mice at a dose of 160 and 320 mg/kg, respectively. We report here on a related series of N4,N4-disubstituted 2-acetylpyridine thiosemicarbazones. Several members of this group bearing alkyl or cycloalkyl substituents at N4 show activity superior to the most active monosubstituted 2-acetylpyridine thiosemicarbazones. However, the greatest improvement in potency was seen when the N4-nitrogen atom was incorporated into a six- or seven-membered ring, such as the piperidine, piperazine, or azabicyclo[3.2.2]nonane systems, to give compounds with curative properties at a dose level as low as 20 mg/kg.     

Synthesis of some Mannich bases of 1-cyclohexylidene-N(1,2-dihydro-2-oxo-3H-indol-3-ylidene) thiosemicarbazones and their antibacterial activity

Some Mannich bases of 1-cyclohexylidene-N(1,2-dihydro-2-oxo-3H-indol-3-ylidene) thiosemicarbazones have been prepared by employing formaldehyde and morpholine and piperidine as secondary amines. These Mannich bases have been characterised on the basis of different physico chemical evidences. Like some alkaloids, they also form reineckate complexes which serve for their estimation. Antibacterial activity of the synthesised Mannich bases has been studied by employing nine bacterial strains. Chloro group at position 5 broadened the spectrum of activity. Compounds with piperidine showed better activity than the compounds with morpholine, against almost all the organisms used (except 1 or 2 occasions).     

The potent and novel thiosemicarbazone chelators di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone and 2-benzoylpyridine-4,4-dimethyl-3-thiosemicarbazone affect crucial thiol systems required for ribonucleotide reductase activity

Di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone possesses potent and selective antitumor activity. Its cytotoxicity has been attributed to iron chelation leading to inhibition of the iron-containing enzyme ribonucleotide reductase (RR). Thiosemicarbazone iron complexes have been shown to be redox-active, although their effect on cellular antioxidant systems is unclear. Using a variety of antioxidants, we found that only N-acetylcysteine significantly inhibited thiosemicarbazone-induced antiproliferative activity. Thus, we examined the effects of thiosemicarbazones on major thiol-containing systems considering their key involvement in providing reducing equivalents for RR. Thiosemicarbazones significantly (p < 0.001) elevated oxidized trimeric thioredoxin levels to 213 ± 5% (n = 3) of the control. This was most likely due to a significant (p < 0.01) decrease in thioredoxin reductase activity to 65 ± 6% (n = 4) of the control. We were surprised to find that the non-redox-active chelator desferrioxamine increased thioredoxin oxidation to a lower extent (152 ± 9%; n = 3) and inhibited thioredoxin reductase activity (62 ± 5%; n = 4), but at a 10-fold higher concentration than thiosemicarbazones. In contrast, only the thiosemicarbazones significantly (p < 0.05) reduced the glutathione/oxidized-glutathione ratio and the activity of glutaredoxin that requires glutathione as a reductant. All chelators significantly decreased RR activity, whereas the NADPH/NADP(total) ratio was not reduced. This was important to consider because NADPH is required for thiol reduction. Thus, thiosemicarbazones could have an additional mechanism of RR inhibition via their effects on major thiol-containing systems.     

磺化槲皮素金属配合物的合成、表征及抗氧化、抗菌活性研究

目的 研究磺化槲皮素金属配合物的合成方法及抗氧化、抗菌活性。方法 通过磺化、金属配位等步骤合成4种槲皮素磺酸金属配合物,以DPPH清除率、抑菌环的大小检测配合物的抗氧化、抗菌活性。结果 槲皮素磺酸锌配合物对金黄色葡萄球菌的抑制作用随浓度的增大而提高,在浓度为7.5 mg·mL^-1时其抑菌环为3.60 mm,对大肠杆菌没有抑制作用,其他磺酸金属配合物的抑菌效果并不明显。槲皮素磺酸金属配合物对DPPH的清除率随浓度的升高而增强,当槲皮素磺酸配合物的浓度达到40 mg·mL^-1时槲皮素磺酸锌配合物、槲皮素磺酸铜配合物、槲皮素磺酸钴配合物和槲皮素磺酸锰配合物清除率分别达到47.55%,91.40%,46.74%,68.22%。结论 通过磺化合成的槲皮素磺酸金属配合物具有抗菌和抗氧化的活性。     

Role of metalation in the topoisomerase IIα inhibition and antiproliferation activity of a series of α-heterocyclic-N4-substituted thiosemicarbazones and their Cu(II) complexes

The topoisomerase-IIα inhibition and antiproliferative activity of α-heterocyclic thiosemicarbazones and their corresponding copper(II) complexes have been investigated. The Cu(II)(thiosemicarbazonato)Cl complexes were shown to catalytically inhibit topoisomerase-IIα at concentrations (0.3-7.2 μM) over an order of magnitude lower than their corresponding thiosemicarbazone ligands alone. The copper complexes were also shown to inhibit the proliferation of breast cancer cells expressing high levels of topoisomerase-IIα (SK-BR-3) at lower concentrations than cells expressing lower levels of the enzyme (MCF-7).