Altromycins, novel pluramycin-like antibiotics. II. Isolation and elucidation of structure.

Abstract

A novel complex of Gram-positive antibiotics was produced from the fermentation of an actinomycete culture AB1246E-26. The antibiotics were recovered from the whole fermentation broth by extraction with organic solvent and isolated using counter-current chromatography. UV and IR data place these compoundshi the anthraquinone-derived class of antibiotics. Mass spectral and NMRdata indicate a new complex of compounds related to, but distinctly different from the pluramycin type antibiotics.In the course of screening soil microorganisms for activity against Pseudomonas aeruginosa, an actinomycete was discovered which produced four new related antibiotics. UVand IR data place these compounds in the anthraquinone-derived class of antibiotics, but their formulae have not been reported among members of this class. NMRstudies indicate that these compounds are related to, but distinctly different from pluramycin type compounds. Previously reported members of the pluramycin class typically have amino sugars connected to carbons 8 and 10 of the D ring on the anthraquinone-y-pyrone nucleus. The altromycins are novel in the occurrence of an unusual disaccharide unit on carbon 10 of the D ring while carbon 8 of the D ring is unsubstituted. The disaccharide unit consists of an amino sugar common to the pluramycins and a neutral O-glycosidic sugar not found in the pluramycins. An additional novel feature seen in these compoundsis the substitution of carbon 13 on the B ring with a neutral C-glycoside. The altromycins differ from one another in the sugar regions of the molecule. The structural characterization of these compoundsis outlined in this paper. Antibiotic production and microbiological data are presented in a companionpaper1}. Isolation

Spectroscopic studies on the anticancer antibiotic Altromycin H and the interaction with copper(II) ions

“…In contrast to the weak antibacterial activity the Altromycins exhibit, in vitro, highly potent cytotoxic activity against a variety of tumor cell lines (A549 Human Lung, HCT-8 Human colon and P388 Leukemia). In vivo Altromycins are active against systemic P388 Leukemia, systemic M5076 ovarian sarcoma, Lewis lung carcinoma as well as human LS174T colon tumor [1].…”

“…Altromycins [1,2] are a complex of Gram positive antibiotics which were produced from the fermentation of an actinomycete culture (strain AB 1246E-26). In contrast to the weak antibacterial activity the Altromycins exhibit, in vitro, highly potent cytotoxic activity against a variety of tumor cell lines (A549 Human Lung, HCT-8 Human colon and P388 Leukemia).…”

Bioactive C-Glycosides from Bacterial Secondary Metabolism

“…(40)) form a distinct group within the pluramycin family. They were first obtained from cultures of actinomycete AB 1246E-26 [217,218]. Altromycins A-D (141 -144) are highly unusual in that the C-glycoside at the C-5 position does not link the sugar directly to an electron-rich aryl ring.…”

Μεταλλικά σύμπλοκα του αντικαρκινικού αντιβιοτικού Altromycin B

“…Κεφάλαιο 2 ο : Το εξεταζόμενo φάρμακο-υποκαταστάτης Altromycin B 2.1 Ανακάλυψη -Απομόνωση -Φυσικές ιδιότητες 4 Οι αλτρομυκίνες είναι μια νέα οικογένεια αντιβιοτικών που εμφανίζουν αντινεοπλαστική δράση και για πρώτη φορά απομονώθηκαν το 1989 στα εργαστήρια της Abbott στο Σικάγο των Η.Π.Α. Είναι φυσικά προιόντα τα οποία απομονώθηκαν από έναν ακτινομύκητα (actinomyces), που ονομάσθηκε Strain AB 1246E-26, και βρέθηκε σε δείγμα χώματος ενός δάσους της Νοτίου Αφρικής.…”

“…Στον C(13) είναι επίσης ενωμένη μια μεθυλο-εστερομάδα, ενώ μια θέση υποκατάστασης αυτού του άνθρακα υποκαθίσταται με -ΟΗ ή -Η δίνοντας τα διαφορετικά είδη αλτρομυκινών, καθώς και στον C(5') έχουμε θέση υποκατάστασης με -ΟΗ ή -Η. δ) Από έναν εποξειδικό δακτύλιο ενωμένο στον C(2) του χρωμοφόρου συστήματος, στον οποίο υπάρχουν δύο μεθυλομάδες σε -trans θέση, όπως έχει διαπιστωθεί με φασματοσκοπία 2D-NMR (NOE-CAMEL experiment) 4 .…”