萘醌类化合物抗肿瘤活性研究进展

萘醌类化合物是一类天然生物活性分子,多数具有抗肿瘤作用.随着该类化合物抗肿瘤作用及其机理的深入研究和逐步阐明,人们合成了许多萘醌衍生物.根据萘醌母体结构的不同,这些化合物可分为萘茜类、1,4-萘醌类和1,2-萘醌类等.本文综述了近年来此类化合物抗肿瘤作用、作用机理、构效关系等研究的新进展.     

Reactions between dialkylamine drugs, 2,3-dichloro-1,4-naphthoquinone and acetaldehyde

Dialkylamine drugs desipramine, propanolol, pindolol, alprenolol and metoprolol 4a-e react with 2,3-dichloro-1,4-naphthoquinone (2) and acetaldehyde to give red coloured 2-dialkylamino-3-chloro-1,4-naphthoquinones 5a, b, d, e, blue coloured 2-dialkylamino-vinyl-3-chloro-1,4-naphtho-quinones 1a-e and bluish green coloured 2-dialkylamino-butadienyl-3-chloro-1,4-naphthoquinones 6b-e. The colour products are isolated by column chromatography.     

Anti-cancer activities of 1,4-naphthoquinones: a QSAR study

Quinone moieties are present in many drugs such as anthracyclines, daunorubicin, doxorubicin, mitomycin, mitoxantrones and saintopin, which are used clinically in the therapy of solid cancers. The cytotoxic effects of these quinones are mainly due to the following two factors: (i) inhibition of DNA topoisomerase-II and, (ii) formation of semiquinone radical that can transfer an electron to oxygen to produce super oxide, which is catalyzed by flavoenzymes such as NADPH-cytochrome-P-450 reductase. Both semiquinone and super oxide of quinones can generate the hydroxyl radical, which is the cause of DNA strand breaks. 1,4-naphthoquinone contains two quinone groups that have the ability to accept one or two electrons to form the corresponding radical anion or di-anion species. It is probably dependent on the quinone redox cycling that yields "reactive oxygen species" (ROS) as well as arylation reactions, which is common to quinones for biological relevance. In the present review, an attempt has been made to collect the cytotoxicity data on different series of 1,4-naphthoquinones against four different cancer cell lines that are L1210, A549, SNU-1, and K562, which were acquired by using identical method, and has been discussed in terms of QSAR (quantitative structure-activity relationships) to understand the chemical-biological interactions. QSAR results have shown that the cytotoxic activities of 1,4-naphthoquinones depend largely on their hydrophobicity.     

2-Dichloromethyl-naphthimidazole quinones. 4. Heterocyclic 1,4-naphthoquinine derivatives

2-Arylamino-3-dichloroacetylamino-1,4-naphthoquinones 4 show in ethanolic hydrochloric acid the same reactivity as the corresponding 3-monochloroacetylamino-1,4-naphthoquinones 3. After cyclisation from 4 to 6, 6 dehydrates to give 2-dichloromethyl-4,9-dihydro-1-phenyl-1H-napth [2,3-d]imidazole-4,9-diones 8. Elimination of dichloromethane from 6 to 9 is not observed. The reaction of 4c in alkaline DMSO solution indicates, that ring closure to 3-hydroxy-benzo[g]quinoxalinetriones 2 is possible. The microbiological activity from 7 and 8 has been proved.     

桑叶降糖有效部位活性成分研究

目的 对桑叶中降糖活性部位进行化学成分研究.方法 利用体外α-糖苷酶活性测定和小鼠高血糖模型筛选降糖活性部位.氨基酸分析仪分析氨基酸组成及含量,利用纤维素、离子交换等色谱柱进行分离纯化,通过NMR、MS等波谱分析手段鉴定化合物结构.结果 桑叶中降糖活性成分主要集中在总碱部位,从中鉴定出15种氨基酸并测定了各种氨基酸含量;此外还分离得到8个化合物,除了以前报道过的DNJ (6)、fagomine (7)、1,4-dideoxy-1,4-imino-D-arabinitol (8)外,其余的分别鉴定为2-methyl-hydrazinecarboxylic acid (1)、zarzissine (2)、N-脒基脯氨酸(3)、去甲莨菪碱(1α,2β 3α,4β-tetrahydroxy-nor-tropane) (4)、grateloupinamide(5).结论 桑叶总碱部位为主要降糖活性成分,并且首次通过氨基酸分析鉴定桑叶总碱中氨基酸的种类和含量,分离出5个生物碱类成分,其中化合物1、2、3为首次从该属植物中分离得到,化合物3为新的天然产物.     

Studies on the antibacterial and antifungal properties of 1,4-naphthoquinones

1. New halogenated 1,4-naphthoquinones were synthesized and together with other known 1,4-naphthoquinones, were screened for antibacterial activity by a turbidimetric method, and for antifungal activity by the diffusion method on agar plates.2. The half-wave potentials and the influence on the oxidative phosphorylation of some of these compounds were determined.3. 2-chloro-3,2'-chloro-ethyl-1,4-naphthoquinone (half-wave potential=-187 mV) was the most active compound, completely inhibiting cell respiration.4. While the natural active naphthoquinones, vitamin K and ubiquinones, possess, as substituent, the electron repelling methyl group, the microbiologically active 1,4-naphthoquinones are substituted, in the quinone moiety, with electron attracting groups such as OH or Cl.5. The half-wave potentials can give only an initial indication of the activity of the compounds studied; a good correlation, on the contrary, can be found between the ultraviolet spectra of such compounds and their activity which seems to depend on the ability of active compounds to exist in an extensively conjugated structure and to form hydrogen bonds.     

Color reactions between trialkylamines and naphthoquinones

Sodium 1,2-naphthoquinone-4-sulphonate (1) reacts with trialkylamines 6a, b by N-desalkylation to give red colored 4-di-alkyamino-1,2-naphthoquinones 3a, b. N,N-Diethylaniline (6f), a phenylogous amine, reacts with 1 to form the blue colored 4-(diethylamino-phenyl)-1,2-naphthoquinone (8). 2,3-Dihalogeno-1,4-naphthoquinones 15A/B produce with triethylamine (6a) the red N-desalkylation products 17A/Ba and the blue colored dehydrogenation products 18A/B. The reactions from trialkylamines 6b-g indicate that only ethyl functions may be dehydrogenated. 2,3-Dihalogeno-1,4-naphthoquinones 15A/B form with N,N-Diethylaniline (6f) blue violet colored CT-complexes and with diethylcyclohexylamine (6g) only blue colored 2-aminovinyl-3-halogeno-1,4-naphthoquinones 20A/B.     

The structure–activity relationship review of the main bioactive constituents of Morus genus plants

Morus genus plants are mainly distributed in the temperate to tropical areas over the world and include 17 species and two subspecies. Due to their excellent pharmacological activity, security in food additives and high value in the national economy, Morus genus plants have drawn more and more attention in recent years. In the light of the references published over the last few decades, flavonoids, benzofurans, stilbenes, and Diels–Alder adducts have been reported to be the main bioactive constituents of Morus genus plants. This review summarizes the compounds with excellent bioactivities isolated from Morus genus plants as well as their structure–activity relationships (SARs), which might be useful for the further research and development of Morus genus plants. The aromatic heterocycles with excellent bioactivities isolated from Morus genus plants as well as their structure–activity relationships (SARs) were summarized.     

Effects of 1,4-naphthoquinone derivatives on red blood cell metabolism

The effect on red blood cell metabolism of a series of substituted 1,4-naphthoquinones has been investigated. 2-Methoxy-1,4-naphthoquinone was found to be a potent oxidative compound, generating hydrogen peroxide in erythrocytes and causing both methemoglobin formation and glutathione depletion in the absence of glucose. Flux of glucose through both glycolysis and the hexose monophosphate shunt was stimulated. 2-Hydroxy- and 2,3-dihydroxy-1,4-naphthoquinone were less oxidative. Both compounds caused oxidation of glutathione and formation of hydrogen peroxide with corresponding stimulation of the hexose monophosphate shunt, but did not cause methemoglobin formation. 2-Hydroxy-3-alkyl-1,4-naphthoquinones were not oxidative but did increase the flux of glucose through glycolysis, possibly reflecting membranal damage. The in vitro oxidative effects of these substances do not correlate with their hemolytic activity in rats, indicating that factors other than oxidative damage are important in mediating the in vivo toxicity of these substances.     

Reactions of isopropyl-alkylamine with 2,3-dichloro-1,4-naphthoquinone and 2,3-dichloro-1,4-naphthoquinone/acetaldehyde

Isopropyl-alkylamines 2 react with 2,3-dichloro-1,4-naphthoquinone (1) to give red 2-chloro-3-isopropyl-alkylamino-1,4-naphthoquinones 3 and with 2,3-dichloro-1,4-naphthoquinone/acetaldehyde to give blue 2-chloro-3-isopropylalkylamino-vinyl-1,4-naphthoquinones 7. It is evident that the formation of 7 is preferred sterically to the formation of 3. The reaction between 2, 1 and acetaldehyde give also red aminoquinones 3 and blue green 2-chloro-3-(4-isopropylalkylamino-buta-1,3-dienyl)-1,4-naphthoquinone like 11.     

Chemical structure and biological activity of polysaccharides from Hibiscus sabdariffa.

Three water-soluble polysaccharides have been isolated from flower buds of Hibiscus sabdariffa L. (HIB 1,2,3). The neutral polysaccharides (HIB 1 and 2) are composed of arabinans and arabinogalactans of low relative molecular mass. The major fraction was investigated by methylation analysis, pectinase-treatment, mild acid hydrolysis and NMR studies, and it was shown to be a pectin-like molecule (Mr = 10(5)d). The main chain is composed of alpha-1,4-linked GalA (24% methyl-esterified) and alpha-1,2-linked Rha. Side chains are built of Gal and Ara and are connected to the main chain via C-4 of every third Rha. Its structure seems to be different from polysaccharide structures described in other species of the Hibiscus genus and the Malvaceae family. All fractions were assayed for possible immune-modulating effects. All fractions showed some activity, but the main acidic fraction was contaminated with lipopolysaccharide, and therefore its shown activity has to be discussed carefully.     

Substituted 1,4-naphthoquinones vs. the ascitic sarcoma 180 of mice

Twelve 1,4-naphthoquinones have been tested against the ascitic form of sarcoma 180 in Swiss mice. Statistical analysis shows that the most important molecular parameter determining their effectiveness in prolonging the life of mice bearing this tumor is their redox potentials. Although the toxicities of the compounds are also related to the redox potentials in the same way, the therapeutic indexes can be increased by adding substituents of greater lipophilicity. The naphthoquinones differ greatly in antitumor activities and may inhibit the growth of malignant cells by different mechanisms.     

Antimicrobial production by strictly anaerobic Clostridium spp.

Antimicrobial resistance continues to rise on a global scale, affecting the environment, humans, animals and food systems. Use of natural antimicrobials has been favoured over synthetic molecules in food preservation owing to concerns over the adverse health effects of synthetic chemicals. The continuing need for novel natural antimicrobial compounds has spurred research to investigate natural sources, such as bacteria, for antimicrobials. The antimicrobial-producing potential of bacteria has been investigated in numerous studies. However, the discovery of antimicrobials has been biased towards aerobes and facultative anaerobes, and strict anaerobes such as Clostridium spp. have been largely neglected. In recent years, genomic studies have indicated the genetic potential of strict anaerobes to produce putative bioactive molecules and this has encouraged the exploration of Clostridium spp. for their antimicrobial production. So far, only a limited number of antimicrobial compounds have been isolated, identified and characterised from the genus Clostridium. This review discusses our current knowledge and understanding of clostridial antimicrobial compounds as well as recent genome mining studies of Clostridium spp. focused at identification of putative gene clusters encoding bacterial secondary metabolite groups and peptides reported to possess antimicrobial properties. Furthermore, opportunities and challenges in the identification of antimicrobials from Clostridium spp. using genomic-guided approaches are discussed. The limited studies conducted so far have identified the genus Clostridium as a viable source of antimicrobial compounds for future investigations.     

Chinon-Amin-Reaktionen, 21. Mitt.1) Photoreaktivität einiger 2-Amino-3-halogen-1.4-naphthochinone

Quinone-Amine Reactions, XXI: Photoreactivity of 2-Amino-3-halogeno-1,4-naphthoquinones 2,3-Dichloro- and 2,3-dibromo-1,4-naphthoquinones react with the secondary amines desipramine ( A ), nor- and protriptyline ( B, C ), maprotiline ( D ) and benzoctamine ( E ) to give the 2-amino-3-chloro- and 2-amino-3-bromo-1,4-naphthoquinone derivatives 2a-e and 5a-e . Daylight dealkylates the amine function of chlorinated aminoquinones 2 exclusively, whereas in the brominated aminoquinones 5 debromination of the C-3 position neighboring the amino group is favored. Interestingly the amine functions of the debrominated products are not dealkylated.     

Umsetzungen von 1.4-Naphthochinonen mit N-substituierten Ethylendiaminen

Quinone-Amine Reactions, IX: Reactions Between 1,4-Naphthoquinones and N-Substituted Ethylenediamines N-Alkylethylenediamines 7a/b react with 1,4-naphthoquinones 6 to give 4-alkylbenzoquinoxalinones 3a/b , which are not accessible by alkylation of unsubstituted benzoquinoxalinones 1. On the other hand, N-arylethylenediamines 7c/d yield arylamino(ethylamino)-1,4-naphthoquinones 10c/d. Intramolecular catalysis of the proton transfer explains the fact that the reaction proceeds considerably slower than that of unsubstituted ethylenediamine (5) .     

A review on phytochemistry and medicinal properties of the genus Achillea

Achillea L. (Compositae or Asteraceae) is a widely distributed medicinal plant throughout the world and has been used since ancient time. Popular indications of the several species of this genus include treatment of wounds, bleedings, headache, inflammation, pains, spasmodic diseases, flatulence and dyspepsia. Phytochemical investigations of Achillea species have revealed that many components from this genus are highly bioactive. There are many reports on the mentioned folk and traditional effects. Although, the medicinal properties of Achillea plants are recognized worldwide, there are only one review article mainly about the structures of the phytochemical constituents of Achillea. The present paper reviews the medicinal properties of various species of Achillea, which have been examined on the basis of the scientific in vitro, in vivo or clinical evaluations. Various effects of these plants may be due to the presence of a broad range of secondary active metabolites such as flavonoids, phenolic acids, coumarins, terpenoids (monoterpenes, sesquiterpenes, diterpenes, triterpenes) and sterols which have been frequently reported from Achillea species.     

Structure-activity relationships in the haemolytic activity and nephrotoxicity of derivatives of 1,2- and 1,4-naphthoquinone

Naphthoquinone derivatives are under investigation as potential therapeutic agents. Some such compounds are known, however, to be toxic to both animals and humans. Many naphthoquinone derivatives are haemolytic agents, while others cause necrosis of tubular epithelial cells. In the present study, the short-term toxicity of 16 derivatives of 1,2- and 1,4-naphthoquinone has been examined in rats in order to give information on structure-activity relationships. All the naphthoquinones except one caused haemolytic anaemia, but only hydroxy and amino derivatives were nephrotoxic. Among derivatives of 2-amino-1,4-naphthoquinone, substitution in the 3-position decreased haemolytic activity and abolished nephrotoxicity. Methylation of the hydroxyl group of 2-hydroxy-1,4-naphthoquinone had a similar effect. In contrast, methylation of the amino group of 2-amino-1,4-naphthoquinone increased the severity of both haemolysis and renal damage. Among the 1,2-naphthoquinones tested, the 4-methoxy and 4-amino derivatives were more toxic than the corresponding 1,4-isomers, although 4-methyl-1,2-naphthoquinone was less toxic than 2-methyl-1,4-naphthoquinone. At present, the toxicity of naphthoquinone derivatives cannot accurately be predicted on the basis of their chemical structure. In developing naphthoquinone derivatives for use in humans, toxicological studies in animals should be conducted at an early stage, bearing in mind that clinical studies have shown that humans appear to be particularly vulnerable to the nephrotoxic action of these compounds, and that certain individuals are unusually susceptible to their haemolytic action.     

2-Amino-1,4-naphthochinone und 4-Amino-1,2-naphthochinone als Nucleophile - ein Vergleich

2-Amino-1,2-naphthoquinones and 4-Amino-1,2-naphthoquinones as Nucleophiles - a Comparison Contrary to the behavior of 4-amino-1,2-naphthoquinone ( 1 ). 2-amino-1,4-naphthoquinone ( 2 ) (Scheme 3) reacts initially with methyleniminium salts by kinetic control to the N-aminomethyl compounds 3 -HX - 6 -HX, which subsequently generate the thermodynamic stable C-Mannich products 7 -HX - 10 -HX. Under the same conditions the 2-N-substituted 1,4-naphthoquinones 11 - 13 immediately yield the 3-aminomethyl derivatives 14 -HX - 16 -HX. Comparative experiments with the isomeric 2-phenylamino-1,4-naphthoquinone ( 12 ) and 4-phenylamino-1,2-naphthoquinone ( 17 ) using different aminomethylation methods always show a higher reactivity of the ortho-quinonoid compound. A similar reactivity pattern was observed for the cyclization of the N-primary and secondary amino-quinones 1,2, 12, 17 - 22 , which produce the tetrahydropyrimidines 23 - 43 with 1 mole of primary amine and 2 moles of formaldehyde.     

Phyllospongia属海绵次级代谢产物及其生物活性研究进展

Phyllospongia属海绵分布较为广泛,其次级代谢产物结构新颖多样,而且活性显著。从该属海绵中发现的次级代谢产物结构类型包括二倍半萜、呋喃萜、溴二苯醚、甾体、磺酸、核苷等类型化合物。其中,二倍半萜类化合物是该属海绵中最为典型的次级代谢产物,而且大多具有较强的生物活性,如细胞毒、抗菌、抗病毒、鱼毒、防附着等,在海绵的化学防御中发挥着重要作用。已有研究对从该属海绵乃至其他海绵中发现活性天然产物及药物先导化合物具有借鉴意义,文中对Phyllospongia属海绵中次级代谢产物的结构及其生物活性进行了简要综述。