S U M M A R YSimple chemical analyses were carried out on I 98 nocardioform bacteria by means of paper-and thin-layer chromatography. The strains considered to belong to the genus Nocardia contained the lipid LCN-A, arabinose and meso-diaminopimelic acid. All the representative strains from the 'Mycobacteriurn ' rhodochrous complex possessed this lipid though in certain cases the characteristic spot had a slightly lower RF value than that of the reference lipid LCN-A from the standard strain of Nocardia asteroides. The genera Actinomadura, Mycobacterium, Oerskovia and Streptomyces did not contain lipid LCN-A and the distribution of the other two chemical characters varied. The method used to detect lipid LCN-A is simple and reliable and permits the separation of nocardias and 'M.' rhodochrous strains from allied taxa. These results correlate well with other trends in the taxonomy of nocardioform bacteria and confirm the value of chemotaxonomic characters, especially lipids, in the classification and identification of these organisms.

Some benzo-iso-a-carbolines were synthesized by modification of the Graebe-Ullmann reaction and examined for antineoplastic activity. The liTumorhemmende Substanzen, 6. Mitt.: Synthese und antineoplastische Eiaenschaften einiger Benzo-iso-a-carboline near, tetracyclic 5,11 -dirnethyl-5H-indolol2,3-blqu~noiine 136, that is related to ellipticine, showed significant antitumor activity against mice P 388 and L 1210 leukemias and against melanoma B 16. --Einige Benzo-iso-a-carboline wurden mittels einer modifizierten GraebeUNmann-Reaktion synthetisiert und auf tumorhemmende Wirkung georuft. Die dem Ellioticin strukturverwandte tetracvclische Verbindung In continuation of our study on the chemistry and biological activity of fused nitrogen heteroaromatic compounds we recently reported on the synthesis of 9H-pyrido[2,3-blindoles (a-carbolines) 12) and 1H-pyrido [2,3-b] indoles (iso-a-carbolines) z3):These compounds can be considered as "tricyclic analogues" of ellipticine 34). They showed, probably because they belong as planar aromatic ring systems to the general group of DNA intercalators, significant activity in vivo against mice Sarcoma Sa 1805) or in vitro against KB tumor cells3).In this paper we report on the synthesis and antitumor properties of the tetra-and pentacyclic benzo-iso-a-carboline systems 8, 13, 16, 23, and 29.The key-intermediates, 1-substituted benzo-and naphthotriazoles 6, 11 and 14, were obtained by heating directly 2-bromopyridine (4) or 2-chloroquinolines 9 with the corresponding naphtho-or benzotriazoles 5 or 10. The required triazoles 6, 11 and 14 were easily separated from the reaction mixture containing also 2-substituted isomers by crystallization.Thermal decomposition of 6, 11, and 14 in polyphosphoric acid (PPA) afforded compounds 7,12, and 15, respectively, which, after quaternization with methyl iodide and basification, gave the final benzo-iso-a-carbolines 8, 13, and 16.Another synthetic way, given on Scheme 2, was used for the 1 1 H-Benzo[i]-a-carboline 22 and 7H-benzo[gl-a-carboline 29 derivatives.The triazoles 21 and 27 were synthesized according to the procedure described earlier2). The thermal decomposition of triazoles 2 1 in PPA yielded benzo-a-carbolines 22, whereas the decomposition of triazole 27 afforded a mixture of products. The required benzo-a-carboline 28 was separated by column chromatography and its structure was confirmed by the 'H-NMR spectrum. The obtained benzo-a-carbolines 22 and 28 were then quaternized with methyl iodide and basified to give the desired benzo-iso-a-carbolines 23 and 29. Pharmacological Results ChemistryFor the synthesis of benzo-a-carbolines, modifications of the Graebe-Ullmann reaction were applied. The synthetic route to 1H-benzo[h]-a-carboline 8,5H-indolo[2,3-bIquinoline 13 and 5H-benzo [5,6]indolo[ 2,3-blquinoline 16 derivatives is depicted in Scheme 1:Compounds 8, 13, 16, 23, and 29 were tested in vitro on KB tumor cells and in vivo in mice bearing P 388 leukemia6! The cytotoxicity in vitro IC50 of the tested compounds is presented in T...

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The degree of binding was determined between deoxyribonucleic acid (DNA) preparations from nocardiae and "rhodochrous" strains and uracil-labeled DNA from three reference strains, Nocardia asteroides N668 and rhodochrous strains N11 and N54. In all cases, good congruence was found between the DNA reassociation data and that from numerical phenetic studies. Only a small degree of nucleotide sequence homology was found between the N . asteroides reference system and the other taxa studied, and there was evidence that N .crsteroides is genetically heterogeneous. The moles percent guanine plus cytosine for the rhodochrous strains was within the range 58 to 67; the corresponding range for nocardiae was 64 to 68 mol%.The confused and tortuous taxonomic history of bacteria variously known as "Mycobacterium" rhodochrous, the "rhodochrous" complex, and the "rhodochrous" taxon was reviewed by Bousfield and Goodfellow (51, who concluded that these organisms form a recognisable taxon equivalent in rank to the genera Corynebacterium, Nocardia, and Mycobacter i u m . The internal structure of the rhodochrous complex is still obscure, but the results of chemical (2, 3, 17), numerical phenetic (17, 39), deoxyribonucleic acid (DNA) reassociation (lo), genetic recombination (l), and serological (24) studies show that subgroups exist.The heterogeneity of the rhodochrous complex is most clearly seen in numerical phenetic studies in which two or more homogeneous phena have been recognised (6,16,17,22,35). However, since few strains are common to all of these investigations, it is difficult to determine whether or not, and to what extent, the phena overlap. In an extensive numerical taxonomic study, Goodfellow and Alderson (J. Gen. Microbiol., in press) divided 150 representative rhodochrous strains into 10 homogeneous subclusters (1A through 15). Subcluster 1A was equated with N . rubra (6), Gordona rhodochroa (38)) and phenon la (17); subclusters 1B and 1E were equated with phena 14B and 14A (16), respectively; subcluster 1D was equated with N . pellegrino (28); subclusters 1F and 1G were equated with phena lc and lb (17), respectively; subcluster 1H was equated with N . erythropolis (6) and phena 14D (16) and F3 (22); and subcluster 1J was equated with bacteria given the trivial name "Lspi" (large, spored, pink, irregular) (15). Subcluster 1C can be subdivided further and contains strains of G. bronchialis, G. rubra, and G . terrae (37).Good congruence has been observed between nucleotide sequence homology and numerical phenetic data in a number of genera including actinomycete taxa (13,19,34). In most cases, taxospecies share at least 70% DNA homology, and lower binding values are considered to reflect significant genetic divergence (12). In an earlier DNA reassociation study, Mordarski et al. (29) found that representatives of G . bronchialis, G . rubra, G . terrae, N . pellegrino (28), and phenon la (17) formed DNAhomology groups. In view of these encouraging results, we have extended our DNA reassociation assays on nocardiofo...

The degree of binding was determined between DNA preparations from gordonae and rhodochrous strains and uracil-labelled DNA from five reference strains, Nocardia asteroides NK20, N. pellegrino PI I , Gordona bronchialis TI, G. terrae T5 and rhodochrous strain ~9 0 .Most of the rhodochrous and pellegrino strains fell into one of two genetically homogeneous taxa. The nucleotide sequence homology data also suggested that G. bronchialis, G. rubra, and more equivocally G. terrae, formed distinct species. However, the values for DNA relatedness between these species, and between them and the rhodochrous homology groups, were comparatively low. Only a small degree of nucleotide sequence homology was found between the N. asteroides reference system and the rest of the taxa studied. The nucleotide composition of the DNA preparations from 29 of the 30 test strains fell between 63 and 69 mol % guanine plus cytosine.

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