Synthesis and Antimicrobial Evaluation of Amino Acid Naphthoquinone Derivatives as Potential Antibacterial Agents

Abstract

Background: The synthesis and biological evaluation of 1,4-naphthoquinone derivatives are of great interest since these compounds exhibit strong antibacterial, antifungal, antimalarial, and anticancer activities. The electronic properties of naphthoquinones are usually modulated by attaching functional groups containing nitrogen, oxygen and sulfur atoms, which tune their biological potency and selectivity. Methods: A series of 13 amino acid 1,4-naphthoquinone derivatives were synthesized under assisted microwave and ultrasound conditions. The antibacterial activity compounds was tested against American type Culture Collection (ATCC): Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Enterococcus faecalis, as well two multidrug resistant pathogens: Escherichia coli and Staphylococcus aureus from clinical isolated. Minimal inhibitory concentration (MIC) was determined using the broth microdilution method. Results: MIC of derivatives 4–11, 14 and 16 showed antimicrobial activity against gram-positive and gram-negative bacteria. Antimicrobial activities of the compounds 4–8 and 14 were ≤MIC 24.7 μg∙mL-1 against all the reference strain, even more the compound 6 showed the most potent activity with a MIC of 3.9 μg∙mL-1 on S. aureus. On the clinical isolated the compounds 7, 8 and 14 showed a MIC of 49.7 and 24.7 μg∙mL-1 against S. aureus y E. coli respectively. About ADME properties and Osiris analysis, the compounds 4-16 presented high gastrointestinal absorption and good characteristics for oral bioavailability and the compound 14 was the less toxic. Conclusion: amino acid 1,4-naphthoquinone derivatives showed good in vitro antibacterial activity against clinical strains, and modifications on C-3 with cloride atom enhanced the efficiency against same pathogens.

Synthesis of 3-((4-Hydroxyphenyl)amino)propanoic Acid Derivatives as Promising Scaffolds for the Development of Antimicrobial Candidates Targeting Multidrug-Resistant Bacterial and Fungal Pathogens

“…The utilization of amino acid derivatives as antimicrobials has been previously suggested by several researchers. Synthetic pathways and compounds have also been explored through diverse chemical approaches and model systems [30][31][32]. Lopez et al conducted a comprehensive investigation into the synthesis and antimicrobial activity of naphthoquinone moieties containing amino acid derivatives [30].…”

“…Synthetic pathways and compounds have also been explored through diverse chemical approaches and model systems [30][31][32]. Lopez et al conducted a comprehensive investigation into the synthesis and antimicrobial activity of naphthoquinone moieties containing amino acid derivatives [30]. Their study revealed promising antimicrobial efficacy against wild-type bacterial strains.…”

Bacillus predominates in the Ophiocordyceps pseudolloydii-infected ants, and it potentially improves protection and utilization of the host cadavers

“…Recent literature has unequivocally shown that fungal secondary metabolites affect the associated microbiome composition and function of the fungi (Deveau et al 2018;Peleg et al 2010,). The synthesis and biological evaluation of naphthoquinone derivatives are of great interest since these compounds exhibit strong antibacterial, antifungal, antimalarial, and anticancer activities (López-López et al 2022). Several naphthoquinone Fig.…”

Novel N,S-Substituted naphthoquinone analogues from aminonaphthoquinones

“…The most important industrial applications of aromatic thiols are as intermediates in the production of pharmaceuticals, agrochemicals, dyes and pigments, and chemicals for the electronics industry (Vollhardt et al 2009;Roy et al 2000). The biological activity properties of amino and thionaphthoquinones are known from the literature (Durán et al, 2023;Kavaliauskas et al, 2022;Liu et al, 2023;López-López et al, 2022;Souza et al, 2023). In this study, novel N,S-substituted naphthoquinone analogues 2, 4, 6, and 8 were synthesized from the reactions of previously known aminonaphthoquinone derivatives 1 (Kalmayer et al 1991), 3 (Tadashi et al 1996, 5 (Vanallan et al 1963), and7 (Fries et al 1922) with allyl mercaptan.…”