Ozonolysis of neem oil: preparation and characterization of potent antibacterial agents against multidrug resistant bacterial strains

Abstract

Neem, Azadirachta indica A. Juss, is endowed with relevant biological properties and its oil contains unsaturated fatty acids that are susceptible to structural modification by oxidative processes such as ozonolysis to form peroxides. Therefore, the aim of this work was the synthesis, physicochemical characterization, study of thermal behavior, and evaluation of the antimicrobial potential of neem ozonated oils. The ozonolysis reaction was performed over different periods of time, in the presence or absence of water at an ozone concentration of 63 mg L⁻¹ O₃/O₂. The samples were characterized by ¹H and ¹³C NMR spectroscopy, acid and iodine values and, DSC and TG/DTG thermal analyses. Additionally, quantitative ¹H NMR spectroscopy was a very successful and useful tool to determine the unsaturation degree of samples. The products showed excellent broad-spectrum antimicrobial activity in comparison to other ozonated oils reported in the literature, with an MIC of <0.5 mg mL⁻¹ for standard E. faecalis and clinical vancomycin resistant E. faecium, 5.0 mg mL⁻¹ for clinical multiresistant K. pneumoniae (KPC), 2 mg mL⁻¹ for standard S. aureus, and 3 mg mL⁻¹ for methicillin-resistant S. aureus (MRSA). This is the first report on the antimicrobial action of neem oil after the ozonation process. The ozonated neem oils were investigated for their cytotoxicity against two normal human cell lines (HaCaT and HCEC). And the results show the products possess low toxicity. Our studies suggest the compounds can find potential application in the treatment of chronic wounds and skin infections.