Antibacterial Spirotetronate Polyketides from an Actinomadura sp. Strain A30804

Abstract

Large scale cultivation and chemical investigation of an extract obtained from Actimonadura sp. resulted in the identification of six previously undescribed spirotetronates (pyrrolosporin B and decatromicins C–G; 7–12), along with six known congeners, namely decatromicins A–B (1–2), BE-45722B–D (3–5), and pyrrolosporin A (6). The chemical structures of compounds 1–12 were characterized via comparison with previously reported data and analysis of 1D/2D NMR and MS data. The structures of all new compounds were highly related to the spirotetronate type compounds, decatromicin and pyrrolosporin, with variations in the substituents on the pyrrole and aglycone moieties. All compounds were evaluated for antibacterial activity against the Gram-negative bacteria, Acinetobacter baumannii and Gram-positive bacteria, Staphylococcus aureus and were investigated for their cytotoxicity against the human cancer cell line A549. Of these, decatromicin B (2), BE-45722B (3), and pyrrolosporin B (7) exhibited potent antibacterial activities against both Gram-positive (MIC90 between 1–3 μM) and Gram-negative bacteria (MIC90 values ranging from 12–36 μM) with weak or no cytotoxic activity against A549 cells.

Chemistry and biology of specialized metabolites produced by Actinomadura

“…51 Additional analogues of this spirotetronate compound series (28)(29)(30)(31)(32)(33)(34)(35), along with those previously reported (24)(25)(26)(27), were isolated from culture extracts of Actinomadura strain A30804. 52 Structure-activity relationship studies of this set of compounds suggested that the presence of at least two chloro-substitutions on the pyrrole ring is important for antibacterial activity. 52 Spirotetronate kijanimicin (36), produced by A. kijaniata, has a broad spectrum of antimicrobial activity against several Grampositive bacteria, anaerobes, P. falciparum, and also exhibited antitumor activity in a mouse lymphatic leukaemia model.…”

“…52 Structure-activity relationship studies of this set of compounds suggested that the presence of at least two chloro-substitutions on the pyrrole ring is important for antibacterial activity. 52 Spirotetronate kijanimicin (36), produced by A. kijaniata, has a broad spectrum of antimicrobial activity against several Grampositive bacteria, anaerobes, P. falciparum, and also exhibited antitumor activity in a mouse lymphatic leukaemia model. [53][54][55][56][57] The aglycone of kijanimicin is decorated with three L-digitoxose moieties and a rare nitro sugar, D-kijanose.…”

“… 51 Additional analogues of this spirotetronate compound series (28–35), along with those previously reported (24–27), were isolated from culture extracts of Actinomadura strain A30804. 52 Structure–activity relationship studies of this set of compounds suggested that the presence of at least two chloro-substitutions on the pyrrole ring is important for antibacterial activity. 52 …”

“… 52 Structure–activity relationship studies of this set of compounds suggested that the presence of at least two chloro-substitutions on the pyrrole ring is important for antibacterial activity. 52 …”

Pyrrole-Containing Alkaloids from a Marine-Derived Actinobacterium Streptomyces zhaozhouensis and Their Antimicrobial and Cytotoxic Activities

“…Alkaloids make up one of the most significant categories of natural products isolated from marine environments [ 15 ]. Among marine alkaloids, pyrroles are a large group of interesting natural products which occur in marine environments, ranging from microorganisms to algae, sponges, and animals [ 16 , 17 , 18 ]. Pyrroles possess a flat and electron-rich aromatic ring, and their structure is susceptible to electrophilic attack and can also interact with a variety of biomolecules via hydrogen bonds as well as π–π stacking interactions [ 19 ].…”