Phytochemical Information and Biological Activities of Quinolizidine Alkaloids in Sophora: A Comprehensive Review.

Quinolizidine alkaloids, a main form of alkaloids found in the genus Sophora, have been shown to have many pharmacological effects. This review aims to summarize the photochemical reports and biological activities of quinolizidine alkaloids in Sophora. The collected information suggested that a total of 99 quinolizidine alkaloids were isolated and detected from different parts of Sophora plants, represented by lupinine-type, cytisine-type, sparteine-type, and matrine-type. However, quality control needs to be monitored because it could provide basic information for the reasonable and efficient use of quinolizidine alkaloids as medicines and raw materials. The nonmedicinal parts may be promising to be used as a source of quinolizidine alkaloid raw materials and to reduce the waste of resources and environmental pollution. In addition, the diversity of chemical compounds based on the alkaloid scaffold to make a biological compound library needs to be extended, which may reduce toxicity and find new bioactivities of quinolizidine alkaloids. The bioactivities most reported are in the fields of antitumor activity along with the effects on the cardiovascular system. However, those studies rely on theoretical research, and novel drugs based on quinolizidine alkaloids are expected.

[Secondary Metabolites from Marine Microorganisms. I. Secondary Metabolites from Marine Actinomycetes].

Review represents data on new active metabolites isolated from marine actinomycetes published in 2007 to 2014. Marine actinomycetes are an unlimited source of novel secondary metabolites with various biological activities. Among them there are antibiotics, anticancer compounds, inhibitors of biochemical processes.

Components of cancer metabolism and therapeutic interventions.

All forms of life share a common indispensible need of energy. The requirement of energy is necessary for an organism not only to survive but also to thrive. The metabolic activities in normal cells rely predominately on mitochondrial oxidative phophorylation for energy generation in the form of ATP. On the contrary, cancer cells predominately rely on glycolysis rather than oxidative phosphorylation. It is long believed that an impairment of mitochondrial oxidative phosphorylation is the cause of this glycolytic phenotype observed in cancers. However, studies in cancer metabolism have revealed that mitochondrial function in many cancers is intact. It has also been observed that cancers utilize various forms of metabolism. The various metabolic phenotypes that are employed by cancer cells have a common purpose, to balance macromolecular biosynthesis and sufficient ATP production in order to support the rapid proliferation rate characteristic of these aberrant cells. These metabolic pathways are attractive targets for possible therapeutic interventions and currently research is underway to meet this end. More importantly, normal cells have essentially the same metabolic requirements as cancer cells so finding an approach to target these metabolic pathways without incurring detrimental effects on normal tissues remains the challenge.

Inhibitory effect of melanogenesis by 5-pentyl-2-furaldehyde isolated from Clitocybe sp.

In the continued search for melanogenesis inhibitors from microbial metabolites, we found that the culture broth of Clitocybe sp. MKACC 53267 inhibited melanogenesis in B16F10 melanoma cells. The active component was purified by solvent extraction, silica gel chromatography, Sephadex LH-20 column chromatography, and finally by preparative HPLC. Its structure was determined as 5- pentyl-2-furaldehyde on the basis of the UV, NMR, and MS spectroscopic analysis. The 5-pentyl-2-furaldehyde potently inhibited melanogenesis in B16F10 cells with an IC50 value of 8.4 microgram/ml, without cytotoxicity.

Lachnellins A, B, C, D, and naphthalene-1,3,8-triol, biologically active compounds from a Lachnellula species (ascomycetes).

In the course of our search for new biologically active metabolites, lachnellin A (1), a metabolite with high cytotoxic and antimicrobial activities, the structurally related lachnellins B, C and D (3, 4, 7), and naphthalene-1,3,8-triol (8), an inhibitor of malate synthase (EC 4.1.3.2), were isolated from submerged cultures of the ascomycete Lachnellula sp. A 32-89. The antimicrobial, cytotoxic and phytotoxic activities of lachnellin A depended on its reactivity and could be abolished by the addition of cysteine. The enzyme inhibiting activity of (8) was due to reactive intermediates during melanization and was no longer observed in the presence of serum albumin. In addition, rac-scytalone (9), (+)-trans-3,4-dihydro-3,4,8-trihydroxy-1 (2H)-naphthalenone (10), 2,5-dihydroxytoluene (11), and (R)-(-)-5-methylmellein (12) were obtained from the same source and biologically characterized.

Metabolic products from microorganisms. 230. Amiclenomycin-peptides, new antimetabolites of biotin. Taxonomy, fermentation and biological properties.

Four new and two known peptide antibiotics containing amiclenomycin (Acm) have been isolated from a culture of Streptomyces venezuelae Tü 2460: L-MeIle-L-Acm (1), L-Ile-L-Acm (2), L-MeVal-L-Acm (3), L-MeIle-L-Acm-L-Gln (4), L-Ile-L-Acm-L-Gln (5) and L-Val-L-Acm-L-Gln (6). These di- and tripeptides exhibited antimicrobial activity on a minimal medium against Gram-negative bacteria, which could be reversed by biotin. It was shown that the antibiotics were decomposed by peptidases to provide amiclenomycin (7) after their uptake into cells of Escherichia coli via peptide-permeases. The antimicrobial activity of the amiclenomycin-peptides was the inhibition of DAPA-aminotransferase by the amiclenomycin-warhead, however, amiclenomycin itself was hardly transported into the cells. Since the amiclenomycin peptides misuse general transport systems, they are presented here as examples for the illicit transport concept.

Improved methods for production, isolation, and assay of two new chlorisoxazoline amino acid antitumor antimetabolites: U-42, 126 and U43, 795.

Improved fermentation and isolation procedures for antitumor antimetabolites U-42,126 and U-43,795 increased drug yields 30-fold. The sensitivity limit of a newly developed assay is 0.03 mug of U-42,126 and 2.0 mug of U-43,795 per ml. The in vitro antimicrobial effect of both drugs was antagonized by histidine.