New piperazine and morpholine derivatives: Mass spectrometry characterization and evaluation of their antimicrobial activity

• Published in: Journal of pharmaceutical and biomedical analysis 2024-08, Vol.246, p.116202, Article 116202
• Main Authors: Acquavia, Maria Assunta, Bonomo, Maria Grazia, Bianco, Giuliana, Salzano, Giovanni, Gaeta, Carmine, Iannece, Patrizia, Di Capua, Angela, Giuzio, Federica, Saturnino, Carmela
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - analysis; Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antimicrobial activity; Gram-Negative Bacteria - drug effects; Gram-Positive Bacteria - drug effects; HRMS; Mass Spectrometry - methods; Microbial Sensitivity Tests - methods; Morpholines - chemistry; Morpholines - pharmacology; MSn; Piperazine - chemistry; Piperazine - pharmacology; Piperazine/morpholine derivatives; Piperazines - chemistry; Piperazines - pharmacology; Structural characterization; Structure-Activity Relationship
• ISSN: 0731-7085; 1873-264X; 1873-264X
• DOI: 10.1016/j.jpba.2024.116202

Recently, pharmaceutical research has been focused on the design of new antibacterial drugs with higher selectivity towards several strains. Major issues concern the possibility to obtain compounds with fewer side effects, at the same time effectively overcoming the problem of antimicrobial resistance. Several solutions include the synthesis of new pharmacophores starting from piperazine or morpholine core units. Mass spectrometry-based techniques offer important support for the structural characterization of newly synthesized compounds to design safer and more effective drugs for various medical conditions. Here, two new piperazine derivatives and four new morpholine derivatives were synthesized and structurally characterized through a combined approach of Fourier transform-ion cyclotron resonance (FT-ICR) and Linear Trap Quadrupole (LTQ) mass spectrometry. The support of both high-resolution and low-resolution mass spectrometric data namely accurate mass measurements, isotopic distribution and MSn spectra, was crucial to confirm the success of the synthesis. These compounds were further evaluated for inhibitory activity against a total of twenty-nine Gram-positive and Gram-negative bacteria to determine the action spectrum and the antimicrobial effectiveness. Results demonstrated compounds’ antimicrobial activity against many tested bacterial species, providing an inhibitory effect linked to different chemical structure and suggesting that the new-synthesized derivatives could be considered as promising antimicrobial agents. [Display omitted] •Mass Spectrometric characterization of piperazine and morpholine derivatives.•Fundamental role of the derivatives structure in their biological activity.•Antimicrobial activity against many food/environment-borne bacterial species.•New-synthesized derivatives are promising candidates as antimicrobial agents.•ESI-LTQ-MS with ESI-FT-ICR-MS significant in derivatives structural characterization.