Accramycin A, a New Aromatic Polyketide, from the Soil Bacterium, Streptomyces sp. MA37

Drug-like molecules are known to contain many different building blocks with great potential as pharmacophores for drug discovery. The continued search for unique scaffolds in our laboratory led to the isolation of a novel Ghanaian soil bacterium, Streptomyces sp. MA37. This strain produces many bioactive molecules, most of which belong to carbazoles, pyrrolizidines, and fluorinated metabolites. Further probing of the metabolites of MA37 has led to the discovery of a new naphthacene-type aromatic natural product, which we have named accramycin A 1. This molecule was isolated using an HPLC-photodiode array (PDA) guided isolation process and MS/MS molecular networking. The structure of 1 was characterized by detailed analysis of LC-MS, UV, 1D, and 2D NMR data. Preliminary studies on the antibacterial properties of 1 using Group B Streptococcus (GBS) produced a minimum inhibitory concentration (MIC) of 27 µg/mL. This represents the first report of such bioactivity amongst the naphthacene-type aromatic polyketides, and also suggests the possibility for the further development of potent molecules against GBS based on the accramycin scaffold. A putative acc biosynthetic pathway for accramycin, featuring a tridecaketide-specific type II polyketide synthase, was proposed.

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Response of Group B Streptococcus to the Combination of Gold Nanoparticles-Erythromycin as a Nanoweapon

International Journal of Infection ◽

10.5812/iji.113204 ◽

2021 ◽

Vol In Press (In Press) ◽

Author(s):

Leila Fozouni ◽

Prastoo Vaezi ◽

Ania Ahani Azari

Keyword(s):

Gold Nanoparticles ◽

Pregnant Women ◽

Rural Areas ◽

Group B Streptococcus ◽

Antibacterial Properties ◽

Diffusion Method ◽

Broth Microdilution ◽

Wide Range ◽

Broth Microdilution Method ◽

Group B

Background: Group B Streptococcus (GBS) causes a wide range of adverse effects in both mothers and infants during pregnancy and after delivery. Objectives: This study aimed to evaluate the effects of erythromycin either alone or in combination with gold nanoparticles (AuNPs) on the clinical GBS isolated from pregnant women. Methods: This descriptive cross-sectional study was performed on 106 women aged 16 - 48 years. After identification of GBS strains by phenotypic and genotypic methods (PCR), erythromycin-resistant isolates were identified using the Kirby-Bauer test and broth microdilution method according to CLSI-2015 guidelines. The antibacterial properties and minimum inhibitory concentration (MIC) of erythromycin (either alone or combined with AuNPs) were assessed by the agar well-diffusion and broth microdilution methods, respectively. Results: The frequency of GBS isolates was significantly high in the pregnant women aged less than 40 years (73.9%) (P = 0.0251), those with a history of abortion (60.9%) (P = 0.038), and residents of rural areas (60%) (P = 0.038). Moreover, 65.2% of the isolates were resistant to erythromycin. The MIC of AuNPs-erythromycin combination required to inhibit the growth of 50% of GBS isolates (MIC50 = 0.25 μg/mL) was significantly lower than the concentration of AuNP-erythromycin required to inhibit the growth of 90% of the isolates (MIC90 = 1 μg/mL) (P = 0.02), indicating a 16-fold lower dose than the values for erythromycin and AuNPs alone. In the agar well-diffusion method, the average diameter of the growth inhibition zone of AuNPs-erythromycin was 2.5-fold greater than that of free erythromycin (P = 0.037). Conclusions: The results showed that the combination of erythromycin with AuNPs increased the antibacterial effects of erythromycin against GBS isolates.

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One-step route to tricyclic fused 1,2,3,4-tetrahydroisoquinoline systems via the Castagnoli–Cushman protocol

Beilstein Journal of Organic Chemistry ◽

10.3762/bjoc.16.121 ◽

2020 ◽

Vol 16 ◽

pp. 1456-1464

Author(s):

Aleksandar Pashev ◽

Nikola Burdzhiev ◽

Elena Stanoeva

Keyword(s):

Succinic Anhydride ◽

Building Blocks ◽

2D Nmr ◽

Bioactive Molecules ◽

Exocyclic Double Bond ◽

Nmr Techniques ◽

One Step ◽

Bridgehead Nitrogen ◽

New Compounds ◽

Isoquinoline Derivatives

The Castagnoli–Cushman reaction of 3,4-dihydroisoquinolines with glutaric anhydride, its oxygen and sulfur analogues was investigated as a one-step approach to the benzo[a]quinolizidine system and its heterocyclic analogs. An extension towards the pyrrolo[2,1-a]isoquinoline system was achieved with the use of succinic anhydride. The results are evidence of an unexplored method for the access of the aforementioned tricyclic annelated systems incorporating a bridgehead nitrogen atom. The structures and relative configurations of the new compounds were established by means of 1D and 2D NMR techniques. The reactions between 1-methyldihydroisoquinoline and glutaric, diglycolic and succinic anhydrides yielded unexpected isoquinoline derivatives containing an exocyclic double bond. The compounds prepared bear the potential to become building blocks for future synthetic bioactive molecules.

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