Antibacterial Activity of Citreamicin-Alpha (LL-E 19085 Alpha) against Gram-Positive Cocci

Abstract

In vitro antibacterial activity of 429 clinical isolates of gram-positive cocci was tested against citreamicin-alpha (LL-E 19085-alpha) by the agar dilution method. The microorganisms consisted of 313 isolates of staphylococci and 116 strains of streptococci. In vitro activity of citreamicin-alpha was compared with ampicillin, augmentin, cephalothin, erythromycin and vancomycin. MICs of citreamicin-alpha for staphylococci ranged between 0.12-4.0 μg/ml and 0.03-0.12 μg/ml for Streptococcus pyogenes. Enterococci, however, were relatively more resistant, requiring 2.0 μg/ml of this drug to inhibit 64% of the 62 isolates tested. In vitro activity of this antibacterial agent was far superior to that of ampicillin, augmentin, cephalothin and erythromycin, but equal to or slightly inferior to that of vancomycin.

Kibdelones: Novel Anticancer Polyketides from a Rare Australian Actinomycete

“…Further to this, gHMBC correlations from the 6-OH to C-5, C-6, and C-7 positioned the phenol on the fully substituted ring D as indicated, and required placement of a coplanar C-8 carbonyl to achieve chelation-as indicated by the highly deshielded and sharp 1 H NMR resonance for 6-OH (d H = 14.23 ppm)-and thereby defined the regiochemistry of the ring E/F fusion. The upfield 13 C NMR chemical shift for the C-1 lactam carbonyl (d C = 156.36 ppm) was consistent with it being peri to a carbonyl/quinone (compare xantholipin) [2] as opposed to the sp 2 -hybridized carbon atom of a hydroquinone (compare actinoplanones and simaomicin). [3,4,5] The 13 C NMR shift for one of the remaining unassigned carbon atoms was indicative of a quinone (d C = 183.4 ppm), and was attributed to C-3-thereby defining ring B as a p-quinone.…”

“…The upfield 13 C NMR chemical shift for the C-1 lactam carbonyl (d C = 156.36 ppm) was consistent with it being peri to a carbonyl/quinone (compare xantholipin) [2] as opposed to the sp 2 -hybridized carbon atom of a hydroquinone (compare actinoplanones and simaomicin). [3,4,5] The 13 C NMR shift for one of the remaining unassigned carbon atoms was indicative of a quinone (d C = 183.4 ppm), and was attributed to C-3-thereby defining ring B as a p-quinone. The four structure fragments described in Figure 1 account for all but three quaternary sp 2 carbon atoms.…”

“…A sequence of COSY and gHMBC correlations from C-28 to C-24 defined the structure fragment for an n-propyl side chain attached to a fully substituted double bond (d C = 105.7 and 156.41 ppm). The deshielded 13 C NMR shift for C-25 (d C = 156.41 ppm) supported attachment of the N À Me (see below), while the shielded character of C-24 (d C = 105.7 ppm) was consistent with chlorine substitution. ROESY correlations from H 2 -26 and H 2 -27 to the N À Me confirmed the spatial proximity of these functionalities (including N À Me substitution to C-25), while a gHMBC correlation from the NÀMe to C-1 (d C = 156.36 ppm) extended this structure fragment to include an amide/lactam moiety.…”

“…The set of gHMBC correlations about H-19 and H-20 clearly defined the tetrasubstituted ring C, and positioned the quaternary C-22 and C-17 as shown. That C-22 was incorporated into a carbonyl (quinone) was apparent from the 13 C NMR shift (d C = 180.7 ppm), while a correlation from the O À Me to C-17 positioned the methoxy moiety as shown. Further to this, gHMBC correlations from the 6-OH to C-5, C-6, and C-7 positioned the phenol on the fully substituted ring D as indicated, and required placement of a coplanar C-8 carbonyl to achieve chelation-as indicated by the highly deshielded and sharp 1 H NMR resonance for 6-OH (d H = 14.23 ppm)-and thereby defined the regiochemistry of the ring E/F fusion.…”

“…A sequence of COSY and gHMBC correlations from C-8 to C-14 defined the structure fragment incorporating ring F. Attachment of O-15 to C-14 in this fragment was inferred from the 13 C NMR shift for this carbon atom (d C = 166.3 ppm), while the deshielded character of C-8 (d C = 183.7 ppm) identified it as a carbonyl. A sequence of COSY and gHMBC correlations from C-28 to C-24 defined the structure fragment for an n-propyl side chain attached to a fully substituted double bond (d C = 105.7 and 156.41 ppm).…”