The synthesis and antimicrobial activities of some 1,4-naphthoquinones (II)

In order to evaluate the antimicrobial effect of 2,3-disubstituted-1,4-naphthoquinone derivatives we newly synthesized several 2-chloro and 2-bromo-3-(substituted)-1,4-naphthoquninones. Amination reaction of 2,3-dihalo-1,4-naphthoquinones with aryl and aliphatic amines in ethanol gave 2-halo-3-(N-alkyl or N-aryl)-1,4-naphthoquinone derivatives (1a,b–10a,b) in 60%–90% yield. These derivatives subjected to antibacterial and antifungal activities,in vitro, againstBacillus subtilis ATCC 6633, Candida albicans 10231 and local, Pseudomonas aeruginosa NCTC10490, Staphylococcus aureus ATCC 6538p, Escherichia coli NIHJ, Aspergillus niger KCTC 1231. Tricophyton mentagrophytes KCTC 6085. Among these derivatives,1b, 6b and7a showed the potent antibacterial activities.1b, 8b and9b have the antifungal activities.1b is most effective in preventing the growth ofBacillus subtilis and Pseudomonas aeruginosa, Candida albicans, Aspergillus niger. Tricophyton mentagrophytes. The several of these compounds demonstrated a broad spectrum of activitiesin vitro.     

Lipophilic naphthols and 1,4-naphthoquinones as inhibitors of prostaglandin synthesis. 6. Study of 1,4-naphthoquinones

A number of plumgagin homologues (2-alkyl-1,4-naphthoquinones) and their 3-methyl derivatives are synthesized to enhance the inhibition of the prostaglandin synthetase (PGS)-activity by the natural compound plumbagin and to minimize its toxicity. The inhibition of the enzyme activity by the new naphthoquinones is only weak but their naphthol precursors are strong PGS-inhibitors. The mechanism of this enzyme interaction by the lipophilic naphthol derivatives is discussed in context with their singlet oxygen (1O2) reactive properties.     

Reviews on 1,4-naphthoquinones from Diospyros L

The genus Diospyros is one of the most important sources of bioactive compounds, exclusively 1,4-naphthoquinones. The following information is an attempt to cover the developments in the biology and phytochemistry of 1,4-naphthoquinones isolated from this genus, as well as the studies done and the suggested mechanisms regarding their activities. During the past 60 years, many of these agents have been isolated from Diospyros L. Twelve considerable bioactive structures are reported in this review. The basic 1,4-naphthoquinone skeletons, on which a large number of studies have been done, are plumbagin and diospyrin. Today, the potential for development of leads from 1,4-naphthoquinones obtained from Diospyros L. is growing dramatically, mainly in the area of anticancer and antibacterial investigations. The data prepared and described here are intended to be served as a reference tool to the natural products and chemistry specialists in order to expand the rational drug design.     

Antipruritic effects of 1,4-naphthoquinones and related compounds

The antipruritic effects of orally administered 1,4-naphthoquinone derivatives and related compounds on compound 48/80-induced scratching behavior in mice were studied. 2-Hydroxy-3-(2-hydroxyethyl)-1,4-naphthoquinone, ferulic acid, 2,2'-methylenebis(3-hydroxy-1,4-naphthoquinone), and 2,2'-ethylidenebis(3-hydroxy-1,4-naphthoquinone) (impatienol) all exhibited significant antipruritic activity. However, 2-methoxy-3-(2-hydroxyethyl)-1,4-naphthoquinone (balsaquinone), which was isolated from a natural source for the first time, did not show any activity. The present results indicate that these compounds are promising for treating allergic diseases with chronic and severe pruritus.     

Synthesis of 2,3-disubstituted 1,4-naphthoquinones as antiplatelet agents

In continuing search for novel antiplatelet agents, the highly potent agent 2-chloro-3-methoxycarbonylethylcarboxamido-1,4-naphthoquinone 2 was selected as lead compound. Structure-activity relationships in this series were examined. Some of these compounds showed significant antiplatelet activities. Further studies on the action mechanism showed that 2-acetamido-3-chloro-1,4-naphthoquinone 4 has a direct inhibitory action on cytosolic phospholipase A(2) (cPLA(2)) activity in platelets.     

Cyclooxygenase-2 inhibitory 1,4-naphthoquinones from Impatiens balsamina L

Significant selective cyclooxygenase-2 (COX-2) inhibitory activities were observed for two new 1,4-naphthoquinone sodium salts, sodium 3-hydroxide-2[[sodium 3-hydroxide-1,4-dioxo(2-naphthyl)]ethyl]naphthalene-1,4-dione (impatienolate) (1) and sodium 2-hydroxide-3-(2-hydroxyethyl)naphthalene-1,4-dione (balsaminolate) (2), which were isolated from the corolla of Impatiens balsamina L. (Balsaminaceae). Their structures were elucidated by spectral techniques. Our results offer evidence supporting the use of I. balsamina L. to treat articular rheumatism, pain, and swelling.     

茉莉酸类的抗癌活性及其作用机制

茉莉酸类属于植物激素,能介导植物对外界伤害和病原菌侵染做出的应激防御反应,并对哺乳类动物癌细胞表现出抗癌活性。茉莉酸甲酯(MJ)是天然茉莉酸类中最有效的抗癌衍生物,能抑制癌细胞的增殖,诱导癌细胞死亡。茉莉酸类还具有引起基因表达异常等其他抗癌活性。本文通过回顾近年来茉莉酸类作为抗癌药物的研究进展,对茉莉酸类的抗癌活性及其作用机制进行了简单介绍。     

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.     

Chemometric approach in a QSAR study: the antibacterial and antimicotic activities of benzofused heteroaromatic derivatives

In order to establish quantitative relationships between the antibacterial activities of a number of thienyl- and furyl-benzimidazoles and benzoxazoles, the biological data were measured homogeneously for a selected set of 16 representative compounds of the available set of 103. The data were analyzed by the PLS method. The results of linear PLS modelling and PLS response surface modelling permitted a straightforward interpretation of the structural features relevant to the activities and the prediction of a possible optimal structure.     

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.     

Quinoxaline 1,4-dioxide: a versatile scaffold endowed with manifold activities

Since 1940s, Quinoxaline 1,4-dioxides (QdNO's) are known as potent antibacterial agents, and subtherapeutic levels have been used to promote growth and improve efficiency of feed conversion in animal feed. They have also shown a selective cytotoxicity against hypoxic cells present in solid tumours. Furthermore, recent studies have put in evidence that QdNO's are endowed with antitubercular, antiprotozoal and anticandida activities. On the other hand, several authors have reported about photoallergic and mutagenic effects of some derivatives. QdNO's may also cause the development of antibiotic-resistant bacteria and influence the horizontal transfer of virulence genes between bacteria. In this review article we report the biological properties, the mode of action and Structure Activity Relationship (SAR) studies of the QdNO derivatives. Furthermore, some cytogenetic and genotoxic effects, classical and more recent method of synthesis, the quinoxaline 1,4-dioxides, and some of their most important reactions, were also reported.     

QSAR, diagnostic statistics and molecular modelling of 1,4-dihydropyridine calcium antagonists: a difficult road ahead.

Quantitative structure-activity relationships of a series of substituted 1,4-dihydropyridine calcium channel antagonists were studied. The analysis is difficult because of the problem of multicollinearity of substituent parameters, a high-leverage point, and position-dependent grouped observations. Canonical regression appears to be the method of choice. With respect to a maximum activity, it was shown that the following rank order of substituent parameters exists: Lipophilicity approximately ortho-position > inductivity > minimum width > meta-position. The molecular conformation of antagonists does not differ markedly (with exception of nifedipine derivatives and nimodipine), but differences seem to exist between the antagonists and the activator BAY K 8644.