Bioactivity and alkaloids

Microorganisms have been used in cancer treatment. As previously mentioned. Moss includes a chapter about the use of a mixed bacterial vaccine, Coley s Toxins, in the treatment of cancer (Moss, 1992, pp. 407 12). Moss considers the discovery of these toxins a remarkable advance in cancer therapy. Interest has been revived in the use of these toxins, as per information supplied by a frequent contributor, Wayne Martin, in issues of the Townsend Letter for Doctors Patients, to be further described. 

Moss has another chapter about the use of MTH-68 vaccine, a unique form of immunotherapy developed by Laszlo K. Csatay, M.D., of Fort Lauderdale, Florida (Moss, 1992, pp. 437 44). It involves the interference between two viruses, which is a well-known phenomenon. One virus interferes with the activities of the other, in one way or another. The situation may also be looked upon as a case where one virus stimulates the immune system to destroy the other less desirable virus, the latter being the cause of the cancerous condition. 

Moss further notes that Csatay and his colleagues published a paper describing the effects of 15 harmless viruses on 4 disease-causing viruses in animals. The results included a marked reduction in the death rate in mice from a strain of rabies, from 50% to 15%. 

The work continues in this general area, leading to such anticancer agents as interferons, interleukins, and TNFs (Moss, 1992, p. 441ff). It has been found that disease-causing virus strains induce TNF in human WBC, and so may the interferons and the interleukins, but the latter, by themselves, have not worked out. This in turn has led to the development of a live virus vaccine called MTH-68N, with encouraging results. 

Another pioneer in immunotherapy is the previously cited Josef Issels, a retired 

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Three of the classes of compounds found from the skin of amphibians have been identified from the skin of bufonids, including Bufo marinus. These are steroids (bufadienolides), biogenic amines (catecholamines, indolylalkylamines and alkaloids) and bioactive peptides and proteins. 

An impressive number of alkaloids and bioactive compounds containing the indolizidine skeleton have been synthesized. These belong principally to three classes which will be separately analyzed. Other natural products not belonging to these classes will be collected in section 11.09.8.3. 

Sari, A., Sariyar, G., Mat, A. and Hirlak, F. 1998. Alkaloids and bioactivity of Papaver lateritium occuring in Turkey. Planta Medica, 64 582. 

Sari A, Sariyar G, Mat A, Hirlak F. Alkaloids and bioactivity of Papaver lateritium occurring in Turkey. Planta Med 1998 64 582. 

A complete review on the synthesis of indolizines has appeared <2000HOU(10)745>. This chapter is an extension of the reviews in CHEC(1984) <1984CHEC-I(4)443> and CHEC-II(1996) <1996CHEC-II(8)237>, mainly focusing on the development of synthetic methods aimed at the synthesis of natural alkaloids and important bioactive compounds containing the indolizidine nucleus. 

Shoeb, M., Celik, S., Jaspars, M., Kumarasamy, Y., MacManus, S. M., Nahar, L., Thoo-Lin, P. K. and Sarker, S. D. 2005. Isolation, structure elucidation and bioactivity of schischkinin, a unique indole alkaloid from the seeds of Centaurea schis-chkinii. Tetrahedron, 61 9001-9006. 

Indole chemistry has already been discussed in Chapter 4. This is one of the major groups of naturally occurring bioactive alkaloids, and can be classified into three main categories tryptamine and its derivatives, ergoline and its derivatives, and (3-carboline and its derivatives. 

Several types of bioactive compounds have been reported from the genus Broussonetia including glycosidase inhibitory alkaloids and aromatase inhibitory or cytotoxic flavonoids. This chapter reviews the biologically active constituents from the genus Broussonetia reported by the end of 2001. 

The bioactive secondary metabolites reported from Broussonetia kazinoki can be classified into major two groups, alkaloids and flavonoids (Table 1), Fig. (1). The Kusano group at Osaka University of Pharmaceutical Sciences in Japan reported over 20 pyrrolidine alkaloids, broussonetines A-H, K-M, O-T, V-X, and Mi, and broussonetinines A and B, four pyrrolidinyl piperidine alkaloids, broussonetines I, J, Ji, and J2, two pyrroline alkaloids, broussonetines U and U, and one pyrrolizidine alkaloid, broussonetine N, from hot water extracts of B. kazinoki [16-24]. As shown in Table 1, some of these alkaloids exhibited strong... 

ACID-CATALYSED EPIMERIZATION OF BIOACTIVE INDOLE ALKALOIDS AND THEIR DERIVATIVES... 

ABSTRACT The acid-catalysed epimerization reaction of bioactive indole alkaloids and their derivatives is reviewed. The three mechanisms, which have been proposed for the (J-carboline-type indole alkaloids, are discussed. Through recent developments, evidence for all three mechanisms has been obtained, which shows the complexity of the epimerization reaction. The epimerization seems to depend on structural features and reaction conditions making it difficult to define one universal mechanism. On the other hand, the isomerization mechanism of oxindole alkaloids has been widely accepted. The acid-catalysed epimerization reaction provides a powerful tool in selectively manipulating the stereochemistry at the epimeric centre and it can also have a marked effect on the pharmacology of any epimerizable compound. Therefore, examples of this reaction in die total synthesis of indole alkaloids are given and pharmacological activities of some C-3 epimeric diastereomers are compared. Finally, literature examples of acid-catalysed epimerization reactions are presented. 

Synthesis of Bioactive Indole Alkaloids and Their Derivatives by Utilizing the Acid-Catalysed Epimerization Reaction... 

A variety of other plant compounds are bioactive as toxins, pro-toxins, sweet or bitter tas-tants, odorants, semiochemicals, enzyme inhibitors, receptor agonists, receptor antagonists or psychoactive agents. The structure and bioactivity of non-alkaloid, non-phenolic and non-terpenoid plant compounds is briefly reviewed below. Some selected structures of cyclic compounds in this category are shown in the Appendix (Section 4). 

There are several reviews referring to manzamine alkaloids [7,31-35]. In this chapter, we will review the structure and source of manzamine alkaloids including the large-scale preparation of manzamine alkaloids for preclinical evaluation. We also discuss the detailed synthesis and bioactivities of manzamine alkaloids. 

A brominated pyrrole-imidazole alkaloid, rac-dibromophakellstatin, has been shown to display selective antitumor activity in vitro with the highest activity on the ovarian cancer cell line OVXF 899L <2007BMCL346>. The chemistry and bioactivity of anti-tubulin agents, either natural or synthetic, having an indole as core nucleus have been reviewed <2007MI209>. 

Gunatilaka AA. Natural products from plant-associated microorganisms distribution, structural diversity, bioactivity, and imph-cations of their occurrence. J. Nat. Prod. 2006 69 509-526. Porter JK. Ergot alkaloids and alkaloids from other endophytes, responsible for causing toxic syndrome in cattle after eating contaminated grass. Prikl. Biokhim. Mikrobiol. 1993 29 51-55. Porter JK. Analysis of endophyte toxins fescue and other grasses toxic to livestock. J. Anim. Sci. 1995 73 871-880. 

Over the past quarter-century more than 10,000 compounds have been reported from marine-derived organisms. These compounds encompass a wide variety of chemical structures including acetogenins, polyketides, terpenes, alkaloids, peptides and many compounds of mixed biosynthesis. A number of excellent books and reviews document the diversity of both structures and bioactivities which have been observed for marine-derived compounds. ... 

Although the chemical constituents of plants of the genus Aconitum have been extensively studied, mainly due to the presence of toxic and bioactive alkaloids, there are only few works regarding the phytochemical composition of A. naviculare. 

Members of the family Amaryllidaceae are widely distributed iir the tropics atrd the warm parts of the temperate regions of the world. They are known for their ornamental value and the production of structurally rmique alkaloids, the Amaryllidaceae alkaloids. Some of these alkaloids possess a wide range of biological activities including antitumor, antiviral, antibacterial, antimalarial, central nervous system diseases, immunomodulatory and anti-inflammatory. This chapter emphasizes the bioactivity and bioactive compounds of African Amaryllidaceae. 

Tyrosine spirolactones are not only promising synthetic intermediates for bioactive natural products such as alkaloids and antibiotics but also synthons useful in peptide chemistry. For example, N-protected tyrosine derivatives 104 and 105, prepared from 2,6-di(ferf-butyl)-4-chloromethylphenol, were electrolyzed at a controlled potential (+1.3-1.4 V Vi. Ag/Ag+) in MeCN to give spirolactones 106 and 107 (64 and 85%, respectively). These spirolactones are used for peptide synthesis, as shown in Scheme 19. 

From the viewpoint of organic synthesis, nature provides us with a number of target molecules, which have novel structures and a variety of biological activities. As already shown in Section II.A, electrochemical oxidation of phenols has been applied successfully to natural products synthesis. Hypervalent (diacyloxyiodo)benzenes have also been proved to be effective for natural products synthesis. Generally, oxidation of o- and p-methoxyphenols in MeOH provides the corresponding o- and p-quinone monoketals, respectively. They are utilized as promising synthons for natural products and related bioactive compounds, as demonstrated by Swenton . Recently, these quinone monoketals have been utilized for syntheses of terpenoids, neolignans, anthraquinones, alkaloids and related compounds. 

K Yoganathan, Alkaloids from Malaysian Kopsia. Chemistry and Bioactivity, Ph. D. Thesis, Univenity of Malaya, Kuala Lumpur, 1997. 

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