Quinaldopeptin, a novel antibiotic of the quinomycin family.

Abstract

Quinaldopeptin, a new type of quinomycin antibiotic, was isolated from the culture of Streptoverticillium album strain Q132-6. The antibiotic exhibited strong in vitro antimicrobial and cytotoxic activity and significantly prolonged the survival time of mice inoculated with a murine tumor. Quinaldopeptin is a symmetric cyclic peptide linked only by peptide bonds and differs from known antibiotics of the quinomycin family by the lack of ester linkage.In our search for microbial metabolites with antitumor activity, a novel antibiotic, quinaldopeptin has been isolated from the cultured broth of Streptoverticillium album strain Q132-6 which was isolated from a soil sample collected in AndhraPradesh, India. The antibiotic was recovered from the fermentation broth by solvent extraction and purified by chromatography. Structural studies combining spectral analysis and chemical degradation disclosed that quinaldopeptin is a symmetric cyclic peptide comprised of 2 mol each of 3-hydroxyquinaldic acid, glycine, sarcosine and a,/?-diaminobutyric acid and 4mol of pipecolic acid. Although quinaldopeptin should be classified in the quinomycin group of antibiotics, it distinctly differs from the known compounds by the lack of an ester linkage. Quinaldopeptin is highly active against Gram-positive bacteria and anaerobes and strongly cytotoxic against cultured B16melanomacells. It prolonged the survival time of mice transplanted with P388 leukemia. This paper describes the isolation, properties, structural determination and biological activities of quinaldopeptin.

Bisintercalator natural products with potential therapeutic applications: isolation, structure determination, synthetic and biological studies

“…Parallel testing of the diacetyl derivative provided similar data. 140 When tested in vitro against melanoma B16 and Moser cells, quinaldopeptin had good activity (IC 50 0.0007 and 0.04 lg mL −1 respectively) and was more potent than chromomycin A 3 against B16 melanoma (IC 50 0.002 lg mL −1 ). In vivo anti-tumour activity tested against lymphocytic leukaemia P388 in mice indicated greater potency than mitomycin C (MED 0.3 mg kg −1 day −1 ).…”

“…140 It has also been isolated as a co-metabolite from a culture broth of actinomyces strain A499. 141 The structure of quinaldopeptin was established using UV, IR and NMR experiments, derivatisation studies and microanalysis.…”

Biosynthetic Modularity Rules in the Bisintercalator Family of Antitumor Compounds

“…Five different genera ( Actinomadura , Micromonospora , Nocardioides , Streptomyces , Streptoverticillium and another unclassified actinomycete isolated from the bark of a birch Betula species) have been described as producers, which belong to four distant families ( Thermomonosporaceae , Micromonosporaceae , Nocardioidaceae and Streptomycetaceae ) [17,18,19,20,21,22]. This taxonomical diversity and the fact that these producer microorganisms were obtained from seas and lands of Africa, Asia and America continents, as well as that four different compounds were isolated just in strains collected in a single country (Japan) (Table 1) implies that probably new producers exist in different ecosystems all over the planet, just waiting for someone to discover them.…”

β‐Amino Acid Biosynthesis

“…For instance, both the (2R,3S) isomer and the (2S,3S) isomer of 2,3-Dab are present in the roots of Lotus tenuis [105]. In addition, 2,3-Dab (68) serves as a constituent in the aciculitins A (75), B (76), and C (77) (Figure 4.13), bicyclic glycopeptides isolated from the marine sponge Aciculites orientalis [106], in the papuamides A (78) and B (79) (Figure 4.13), cyclic depsipeptides isolated from sponges of the genus Theonella [107], and in quinaldopeptin, a cyclopeptide from Streptoverticillium album Q132-6 [108]. Capreomycidine (69) is a cyclic guanidino amino acid occurring as a constituent of the tuberculostatic capreomycins [42] and the structurally closely related compounds LL-BM547a, LL-BM547b [46], the tuberactinomycins [41], and viomycin (34) [40] ( Figure 4.4), while streptolidine (70) is present in the streptothricins, for instance in streptothricin F (33) [39] (Figure 4.3), broad-spectrum peptidyl nucleoside antibiotics that were isolated from Streptomyces lavendulae.…”