1,4-Naphthoquinone Analogues: Potent Antibacterial Agents and Mode of Action Evaluation

Abstract

1,4-Naphthoquinones have antibacterial activity and are a promising new class of compound that can be used to treat bacterial infections. The goal was to improve effective antibacterial agents; therefore, we synthesized a new class of naphthoquinone hybrids, which contain phenylamino-phenylthio moieties as significant counterparts. Compound 4 was modified as a substituted aryl amide moiety, which enhanced the antibacterial activity of earlier compounds 3 and 4. In this study, five bacterial strains Staphylococcus aureus (S. aureus), Listeria monocytogenes (L. monocytogenes), Escherichia coli (E. coli), Pseudomonas aeruginosa (P. aeruginosa) and Klebsiella pneumoniae (K. pneumoniae) were used to evaluate the antibacterial potency of synthesized naphthoquinones using the minimal inhibitory concentration (MIC) method. Most of the studied naphthoquinones demonstrated major antibacterial activity with a MIC of 15.6 µg/mL–500 µg/mL. Selected compounds (5a, 5f and 5x) were studied for the mode of action, using intracellular ROS generation, determination of apoptosis by the Annexin V-FITC/PI assay, a bactericidal kinetic study and in silico molecular modelling. Additionally, the redox potentials of the specified compounds were confirmed by cyclic voltammetry (CV).

A novel series of chlorinated plastoquinone analogs: Design, synthesis, and evaluation of anticancer activity

“…Among them, quinone moiety is one of the most important structures in drug discovery (Wellington, Kolesnikova, Nyoka, & McGaw, ). The studies of 1,4‐quinones have drawn a great deal of attention since their scaffold is an important pharmacophore (Jin, Ryu, Moon, Cho, & Yun, ; Lien, Huang, Teng, Wang, & Kuo, ; Ravichandiran, Masłyk et al, ; Ravichandiran, Sheet, Premnath, Kim, & Yoo, ) and amply found in numerous natural products. The first model from nature, prenylquinones, is an important class of compounds occurring in all living cells that contain characteristic 1,4‐quinone and isoprenyl moieties.…”

1,4-Naphthoquinones: Some Biological Properties and Application

“…10) which contain phenylamino-phenylthio moieties as significant counterparts demonstrated major antibacterial activity against bacterial strains Staphylococcus aureus, Listeria monocytogenes, E. coli, P. aeruginosa, Salmonella bongori and Klebsiella pneumoniae. [57][58][59] Two naphthoquinone derivatives (38) and (39) (Fig. 10) had potential antimycobacterial activity against three Mycobacterium tuberculosis strains and did not exhibit cross-resistance with isoniazid and rifampicin; they could be promising scaffolds for the development of new therapeutic strategies against tuberculosis.…”

Design, Synthesis and Antimicrobial Evaluation of New Norfloxacin-Naphthoquinone Hybrid Molecules

“…Quinone, and mainly 1,4-naphthoquinone structures, are widely diffused in several structures of natural products and are often associated to a series of biological activities, including antibacterial [4], antifungal [5], antimalarial and anticancer properties, correlated to their high reactivity due to redox and acid/base behavior.…”

“…Hybrid molecules involving norfloxacin [6,7] and quinones [4,[8][9][10][11] have been studied as antimicrobial agents but, to the best of our knowledge, no data have been reported so far on hybridization taking in account norfloxacin and naphtoquinone structures simultaneously. We report here on the synthesis of new hybrid norfloxacin-quinone derivatives, their in vitro antimicrobial activities and a computational analysis of the complexes with S. aureus DNA-gyrase.…”

“…In vitro antimicrobial activities of precursors norfloxacin (1) and quinones(2)(3)(4), and hybrid molecules 5-7 as sodium salts, expressed in inhibition diameter.…”