Compounds Showing Various Biological Activities

The present report is devoted to recent developments in many natural products derived from marine invertebrates, with emphasis given to those metabolites which show biological activity. As it is impossible to decide whether a newly described substance for which no activity is mentioned is inactive or whether such a substance has not been tested, several such metabolites are included as well as chemically related compounds with various biological activities. The literature since 1980 dealing with isolation of organic compounds will be reviewed. Papers dealing with syntheses are cited only when they provide confirmation for the proposed structure of a natural product. Metabolites from dinoflagellates and the paralytic shellfish poisons will not be discussed because of an extensive review by Shimizu in a recent volume of this series (32). 

Compounds showing vitamin K activity are substituted naphthoquinones. The parent compound, 2-methyl-1,4-naphthoquinone, does show some biological activity as do other similar but synthetic compounds. The production of the complete naturally active forms is thought to depend upon the addition of an isoprene chain at position 3 on the aromatic ring. Differences in this side chain produce the various K vitamins (Figure 12.10). A most important physiological role of vitamin K is in the synthesis of the blood clotting factors, II (prothrombin), VII, IX and X. 

Analysis of the data on the chemistry of isomeric thienopyrimidines published over the last 10-15 years shows that this class of heteroaromatic compounds, which are structural analogs of natural compounds of the purine class, attracts increasing interest of chemists and biochemists. In the first half of the 21st century, new approaches to the synthesis of derivatives of these fused heterocyclic systems will be, undoubtedly, extensively developed. These derivatives are not only of theoretical interest but also possess a broad spectrum of practical use, primarily, due to various biological activities. Of the approaches to their synthesis, multicomponent cascade heterocyclization, which allows one to construct various functionalized thienopyrimidines and their fused analogs in one technologically and ecologically safe step, holds the most promise. 

In reference to the chemical structure of NTN 15192 and NTN 16543, various N-alkyl compounds tvere tested (Table 16.2.2). However, none of the derivatives introducing those alkyls, such as methyl, ethyl, n-propyl, n-butyl, i-butyl, t-butyl, showed any biological activities. In contrast, i-propyl and s-butyl in the N-alkyl of the substructure showed obvious activity to R. solani. 4-Cl substitution at the benzyl ring was effective, but methyl or no substitution showed no effectiveness. Compounds substituted at phenyl ring were not effective as well. 

For a detailed description of spectral map analysis (SMA), the reader is referred to Section 31.3.5. The method has been designed specifically for the study of drug-receptor interactions [37,44]. The interpretation of the resulting spectral map is different from that of the usual principal components biplot. The former is symmetric with respect to rows and columns, while the latter is not. In particular, the spectral map displays interactions between compounds and receptors. It shows which compounds are most specific for which receptors (or tests) and vice versa. This property will be illustrated by means of an analysis of data reporting on the binding affinities of various opioid analgesics to various opioid receptors [45,46]. In contrast with the previous approach, this application is not based on extra-thermodynamic properties, but is derived entirely from biological activity spectra. 

Substituted amino naphthols were synthesized with reactions of 1-naphthols and the appropriate aldehydes. Some new 2,4-disubstituted-3,4-dihydro-2/f-naphth [i,2-e][i,i]oxazines that are expected to show biological activities were obtained by the ring-closure reactions with these aminonaphthols and various aldehydes. In addition, substituted-1,3-amino-hydroxy compounds, 2, can be used in chiral ligands synthesis. 

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