Antimicrobial screening involving Helicobacter pylori of nano-therapeutic compounds based on the amoxicillin antibiotic drug

Helicobacter. 2023 Oct;28(5):e13004. doi: 10.1111/hel.13004. Epub 2023 Jun 30.

Abstract

Nano-structure Cu(II) complex [Cu(AMAB)2 ]Cl2 with Schiff base (AMAB) derived from the condensation between 4-(dimethylamino)benzaldehyde and amoxicillin trihydrate was prepared. (AMAB) Schiff base and its Cu(II) complex were identified and confirmed by different physicochemical techniques. The Schiff base (AMAB) was coordinated to copper ion through carbonyl oxygen and imine nitrogen donor sites. X-ray powder diffraction shows a cubic crystal system of the Cu(II) complex. The density functional theory was used to optimize the structure geometries of the investigated compounds. The molecular docking of the active amino acids of the investigated proteins' interactions with the tested compounds was evaluated. The bactericidal or bacteriostatic effect of the compounds was screened against some bacterial strains. The activity of Cu-chelate against Gram-negative bacteria was mainly more effective than its (AMAB) ligand and vice versa in the case of Gram-positive bacteria. The biological activity of the prepared compounds with biomolecules calf thymus DNA (CT-DNA) was determined by electronic absorption spectra and DNA gel electrophoresis technique. All studies revealed that the Cu-chelate derivative exhibited better binding affinity to both CT-DNA than the AMAB and amoxicillin itself. The anti-inflammatory effect of the designed compounds was determined by testing their protein denaturation inhibitory activity spectrophotometrically. All obtained data supported that the designed nano-Cu(II) complex with Schiff base (AMAB) is a potent bactericide against H. pylori, and exhibits anti-inflammatory activity. The dual inhibition effects of the designed compound represent a modern therapeutic approach with extended spectrum of action. Therefore, it can act as good drug target in antimicrobial and anti-inflammtory therapies. Finally, H. pylori resistance to amoxicillin is absent or rare in many countries, thus amoxicillin nanoparticles may be beneficial for countries where amoxicillin resistance is reported.

Keywords: Helicobacter pylori; 4-(dimethylamino)benzaldehyde; TEM; amoxicillin. CT-DNA; nano-size.

MeSH terms

  • Amoxicillin / pharmacology
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology
  • Anti-Infective Agents* / pharmacology
  • Copper / chemistry
  • Copper / pharmacology
  • DNA / chemistry
  • DNA / metabolism
  • Helicobacter Infections* / drug therapy
  • Helicobacter pylori* / metabolism
  • Humans
  • Microbial Sensitivity Tests
  • Molecular Docking Simulation
  • Schiff Bases / chemistry
  • Schiff Bases / pharmacology

Substances

  • Schiff Bases
  • Copper
  • Amoxicillin
  • Anti-Infective Agents
  • Anti-Bacterial Agents
  • DNA