Modulating Antimicrobial Activity by Synthesis: Dendritic Copolymers Based on Nonquaternized 2-(Dimethylamino)ethyl Methacrylate by Cu-Mediated ATRP

The synthesis of novel star-like heteroarms polymers A­(BC)_<i>n</i> containing m-PEG (block A), methylmethacrylate (MMA), and nonquaternized 2-(dimethylamino)­ethyl methacrylate (DMAEMA) (blocks BC) is here reported. We demonstrated that copolymer films with comparable amounts of DMAEMA have antimicrobial properties strongly depending on the topological structure (i.e., the number of arms) of the composing copolymers. We interpret the highest antimicrobial activity of A­(BC)₂ with respect to A­(BC)₄ and linear copolymers (respectively, A­(BC)₂ ≥ A­(BC)₄ > A­(BC)) as probably due to the formation of strong hydrogen bonds between close amino-ammonium groups in the A­(BC)₂ film. Strong hydrogen bonds seem to be somewhat disfavored in the case of the linear species by the difference in both polymer architecture and film morphology compared with the A­(BC)₂ and A­(BC)₄ architectures

Synthesis and biological evaluation of the progenitor of a new class of cephalosporin analogues, with a particular focus on structure-based computational analysis - Fig 3

<p><b>Effect on cell viability of MRC5 and HepG2 cells after 24 h exposure to compound 8 (dose-range 0.5–50 μg/mL) (A) or ceftriaxone (dose-range 1–50 μg/mL) (B).</b> Data are reported as mean ± SD from two or three independent experiments each in triplicate. Vehicle (DMSO), at the highest concentrations used (0.2 and 0.4% v/v), induced a significant reduction of cell viability of 20% and 12% in MRC5 and HepG2 cells, respectively (not shown). *p<0.05 vs. the respective vehicle.</p

MIC and MLD (in μg/mL) obtained for compound 8 in comparison with ceftriaxone.

<p>MIC and MLD (in μg/mL) obtained for compound 8 in comparison with ceftriaxone.</p

Results of covalent docking between beta lactam antibiotics and selected PBPs of Gram positive bacteria.

<p>Results of covalent docking between beta lactam antibiotics and selected PBPs of Gram positive bacteria.</p

Retrosynthetic strategy for title compound 8.

<p>Retrosynthetic strategy for title compound 8.</p

List of the structures of PBPs selected for the computational analysis.

<p>List of the structures of PBPs selected for the computational analysis.</p

Results of covalent docking between beta lactam antibiotics and selected PBPs of Gram negative bacteria.

<p>Results of covalent docking between beta lactam antibiotics and selected PBPs of Gram negative bacteria.</p