Recent studies on natural products as anticancer agents

Cancer will be the major cause of death in the 21st century and natural products should provide novel and more effective anticancer agents. This review deals with new natural molecules liable to become anticancer drugs, as well as recent specific strategies for a selective treatment of cancer. The introduction presents the current state of the art on anticancer research. Beside, in the following subheadings we summarize our research on cytotoxic natural quinone methide-triperpenes and their analogues. We also discuss our results on the anti-tumour promoting activity of natural naphthoquinones and their derivatives.     

Marine natural products as lead anti-HIV agents

Current anti-HIV drugs have extreme side effects and resistance to these drugs develops rapidly. The marine environment holds an unprecedented number of unusual chemical structural classes with activity against HIV. We review the literature on anti-HIV activity of marine natural products and discuss the efficacy of different structural classes.     

Recent pharmacological studies on natural products in China

Natural products have been used as medicinal agents for many years. In addition, these compounds have also served as the starting points for semisynthetic analogs with improved properties. This review focuses on recent advances in the pharmacological studies on natural products mainly performed and published in China. Emphasis will be placed on those compounds that show the greatest promise clinically such as huperzine A (9-amino-13-ethylidene-11-methyl-4-azatricyclo[7.3.1.0(3.8)]trideca-3(8),6,11-trien-5-one), s-(−)-3-n-butylphthalide (s-(−)-3-butyl-1(3H)-isobenzofuranone), (−)-clausenamide (3-hydroxy-4-phenyl-5a-hydroxybenzyl-N-methyl-γ-lactam) and Ginkgo biloba extract and its active components.     

Pro-oxidant natural products as anticancer agents

Cancer cells produce high levels of reactive oxygen species (ROS) that lead to a state of increased basal oxidative stress. Since this state of oxidative stress makes cancer cells vulnerable to agents that further augment ROS levels, the use of pro-oxidant agents is emerging as an exciting strategy to selectively target tumor cells. Natural products have provided a significant contribution to the development of several drugs currently used in cancer chemotherapy. Although many natural products are known to affect the redox state of the cell, most studies on these compounds have focused on their antioxidant activity instead of on their pro-oxidant properties. This article provides an overview of natural products with pro-oxidant and anticancer activities, with special focus on plant secondary metabolites, and discusses their possible use as cancer chemotherapeutic agents.     

International Research Congress on natural products as medicinal agents

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International Research Congress on natural products as medicinal agents

     

Iminosugar glycosylation inhibitors as anti-HIV agents

Summary A novel class of compounds which are potent inhibitors of the posttranslational glycan trimming enzyme -glucosidase I have been found to display anti-HIV activity. These compounds are iminosugar analogs ofd-glucose, with the oxygen in the ring replaced by a nitrogen, and were originally isolated from plants and microorganisms, although a considerable number of analogs have been synthesized during the past few years. One of these compounds,N-butyl-1-deoxynojirimycin (Bu-DNJ), is presently under evaluation in clinical trials for the control of HIV infections. Cumulative data, to date, suggest that compounds such asN-Bu-DNJ have a hierarchy of effects, with reduction in syncytia formation being the predominant feature, and are known to alter glycosylation of the HIV-1 envelope glycoproteins gp120 and gp41. Consequently, there are a number of different ways in which iminosugars may be exerting an antiviral effect. This paper discusses the basic properties of this class of compounds and the changes they effect in posttranslational processing of gp120 and gp41, as well as the synthesis and characterization of prodrug forms of Bu-DNJ (e.g.N-butyl-6-phospho-1-deoxynojirimycin), which do not inhibit intestinal disaccharidases and may be useful for eliminating the intestinal discomfort and diarrhea associated with administration of -glucosidase inhibitors.     

天然产物中抗HIV生物碱类化合物的研究进展

近年来,从天然产物中寻找高效低毒的先导化合物已成筛选抗HIV药物的重要研究方向。生物碱类化合物作为一类重要的天然产物,数量众多,结构类型复杂,其中有多种抑制和阻断HIV感染的有效成分,通过实验室研究工作和临床用药观察,有望从中获得抗HIV的有效药物。以生物碱类化合物的化学结构为基础,将生物碱类化合物分为异喹啉类、喹啉类、大环类、哌啶类、莨菪烷类、吲哚类、咔唑类、海洋多环胍类、萜类、manzamine型生物碱等10类,对其抗HIV活性进行综述。     

Developing G-quartet oligonucleotides as novel anti-HIV agents: focus on anti-HIV drug design

Recently, a new class of oligonucleotides, forming G-quartet structures, has been developed as novel anti-HIV agents. Several critical structure-activity relationships between HIV-1 integrase and G-quartet oligonucleotides have been demonstrated. In addition the mechanism of the inhibition of HIV-1 integrase by G-quartet oligonucleotides, such as T30695 and its derivatives, has been explored. This review summarises the preliminary studies of developing G-quartet oligonucleotides as novel anti-HIV agents in several aspects including structure-activity relationship, stability-activity correlation, mechanism of HIV-1 integrase inhibition, substitution of phosphorothioates and targeting HIV-1 integrase in infected cells, which, hopefully, could help for developing a novel, efficient anti-HIV agent.     

Developing G-quartet oligonucleotides as novel anti-HIV agents: focus on anti-HIV drug design

Recently, a new class of oligonucleotides, forming G-quartet structures, has been developed as novel anti-HIV agents. Several critical structure-activity relationships between HIV-1 integrase and G-quartet oligonucleotides have been demonstrated. In addition the mechanism of the inhibition of HIV-1 integrase by G-quartet oligonucleotides, such as T30695 and its derivatives, has been explored. This review summarises the preliminary studies of developing G-quartet oligonucleotides as novel anti-HIV agents in several aspects including structure-activity relationship, stability-activity correlation, mechanism of HIV-1 integrase inhibition, substitution of phosphorothioates and targeting HIV-1 integrase in infected cells, which, hopefully, could help for developing a novel, efficient anti-HIV agent.     

Recent patents on live bacteria and their products as potential anticancer agents

This review intends to provide a comprehensive coverage of the various patents, published or issued, since 2007 on live or attenuated bacteria as potential anticancer agents, as well as microbial products including toxins, enzymes, antibiotics, various proteins and peptides as well as other small molecular weight products. Below is a list of such published/issued patents and a summary of the main contents of many such patents.     

6-Aminoquinolones as new potential anti-HIV agents

A series of 6-aminoquinolone compounds were evaluated for their in vitro activity against human immunodeficiency virus type 1 (HIV-1). Compound 12a, bearing a methyl substituent at the N-1 position and a 4-(2-pyridyl)-1-piperazine moiety at the C-7 position, was the most active in inhibiting HIV-1 replication on de novo infected C8166 human lymphoblastoid cell lines. The 12a EC(50) value was 0.1 microM, a 7-20-fold lower concentration relative to that for compounds 8a and 7a containing a cyclopropyl and tert-butyl substituent at the N-1 position, respectively. When the C-6 amino group was replaced with a fluorine atom, a decreased antiviral effect was observed. The observed effects are selective, since potency is substantially reduced when testing the compounds against the herpes simplex virus type 1 (HSV-1). Active quinolone derivatives very efficiently interact with TAR RNA, which suggests a nucleic acid-targeted mechanism of action.     

Plant-derived terpenoids and analogues as anti-HIV agents

The plant-derived terpenoids and analogues are reviewed with respect to their anti-HIV activity, structure-activity relationships, and mechanism of action. The active compounds include diterpenoid lactones, phenolic diterpenes, atisane and kaurane diterpenes, phorbol diterpenes, triterpene glycosides, friedelane triterpenes, taraxerane triterpenes, ursane triterpenes, lanostane triterpene, lupane triterpenes, seco-ring A triterpenes, degraded triterpenes, and cucurbitacin triterpenes. Positive new leads for drug development will be highlighted.     

Synthetic studies on heterocyclic natural products

This article reviews past and ongoing research in the author's laboratory directed toward the synthesis of natural products displaying an azaspirocyclic framework, or incorporating a medium-ring nitrogen heterocycle. New synthetic technologies were devised in order to address the synthetic problems posed by the target molecules. Thus, efforts in the area of azaspirocyclic substances have relied on an oxidative amidation of phenols promoted by iodobenzene diacetate, whereas access to medium-ring nitrogen heterocycles has been secured by means of a ring expansion sequence that relies on the fragmentation of an aziridine triggered by a homo-Brook transposition. Details of the development of these technologies are presented, together with applications to the total synthesis of FR-901483, TAN-1251C, cylindricines, and mitomycinoids.     

Clinical trials of natural products as chemopreventive agents for prostate cancer

Epidemiological research on prostate cancer risk in men throughout the world has identified significant correlations between dietary habits and prostate cancer occurrence. These studies served as a catalyst for exploration into the potential of dietary substances to act as chemopreventive agents against this disease, and include green tea catechins, lycopene, soy isoflavones, pomegranate phenolics, selenium, vitamins E and D, curcumin and resveratrol. Before these agents (in the dietary or purified forms) can be recommended as useful chemopreventive strategies for patients, their activity must be confirmed in rigorously designed clinical trials. This review discusses the preclinical and clinical data available for these dietary agents and describes relevant clinical trials currently being conducted.     

Natural resins and bioactive natural products thereof as potential antimicrobial agents

Natural products and their derivatives have historically been invaluable as a source of therapeutic agents and have contributed to the discovery of antimicrobial agents. However, today with the development of drug-resistant strains, new scaffolds and new sources of bioactive compounds are needed. To this end, plant derived natural resins are reviewed for their potential application as antimicrobial agents. Natural gums, extracts of the whole resins, as well as specific extracts, fractions, essential oils and isolated compounds from the above resins are discussed in terms of their antifungal, antibacterial, and antiprotozoal activity.     

Synthesis of polyketide natural products and analogs as promising anticancer agents

Recent highlights in the synthesis of polyketide natural products and structural analogs as promising anticancer agents are described, focusing on the halichondrins and eribulin (Eisai), together with recently published research on bryostatin, dictyostatin, spongistatin, peloruside, spirastrellolide, palmerolide, reidispongiolide, spirangien and saliniketals. These examples demonstrate the centrality of bioactive polyketides in current and future anticancer drug discovery, and the increasingly key role of efficient total synthesis in providing a sustainable supply of such compounds for drug development.