AI Article Synopsis
- - A series of 12 PEG-alkynyl C2-adenosine conjugates were created using a Sonogashira coupling method and characterized by NMR and mass spectrometry.
- - The conjugates mostly showed low to moderate toxicity in mouse immune cells and had variable effectiveness against different bacteria, with 12c inhibiting Mycobacterium aurum but not Mycobacterium bovis BCG.
- - Two conjugates, 10b and 11b, exhibited high water solubility and increased cAMP levels in cells, and docking studies indicated they had strong binding to specific adenosine receptors, maintaining good binding properties despite the PEG attachments.
Article Abstract
A series of 12 novel polyethylene-glycol(PEG)-alkynyl C2-adenosine(ADN) conjugates were synthesized using a robust Sonogashira coupling protocol and characterized by NMR spectroscopy and mass spectrometry analysis. The ADN-PEG conjugates showed null to moderate toxicity in murine macrophages and 12c was active against Mycobacterium aurum growth (MIC = 62.5 mg/L). The conjugates were not active against Mycobacterium bovis BCG. Conjugates 10b and 11b exhibited high water solubility with solubility values of 1.22 and 1.18 mg/ml, respectively, in phosphate buffer solutions at pH 6.8. Further, 10b and 11b induced a significant increase in cAMP accumulation in RAW264.7 cells comparable with that induced by adenosine. Analogues 10c, 11c and 12c were docked to the A , A , A and A adenosine receptors (ARs) using crystal-structures and homology models. ADN-PEG-conjugates bearing chains with up to five ethyleneoxy units could be well accommodated within the binding sites of A , A and A ARs. Docking studies showed that compound 10b and 11b were the best A receptor binders of the series, whereas 12c was the best binder for A AR. In summary, introduction of hydrophilic PEG substituents at the C2 of adenine ring significantly improved water solubility and did not affect AR binding properties of the ADN-PEG conjugates.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10087458 | PMC |
| http://dx.doi.org/10.1111/cbdd.14128 | DOI Listing |
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