Synthesis and Microbiological Evaluation of New 2- and 2,3-Diphenoxysubstituted Naphthalene-1,4-diones with 5-Oxopyrrolidine Moieties

Abstract

New 3-substituted 1-(3-hydroxyphenyl)-5-oxopyrrolidine derivatives containing hydrazone, azole, diazole, oxadiazole fragments, as well as 2-phenoxy- and 2,3-diphenoxy-1,4-naphthoquinone derivatives were synthesized. The structure of all compounds has been confirmed by NMR, IR, mass spectra, and elemental analysis data. Methyl 1-{3-[(3-chloro-1,4-dioxo-1,4-dihydro-2-naphthalenyl)oxy]phenyl}-5-oxo-3-pyrrolidinecarboxylate demonstrated potential antibacterial and antifungal activities as determined by diffusion and serial dilution methods, while N'-[(4-bromophenyl)methylidene]-1-{3-[(3-chloro-1,4-dioxo-1,4-dihydro-2-naphthalenyl)oxy]phenyl}-5-oxo-3-pyrrolidinecarbohydrazide and 2-{3-[4-(1,2,3-oxadiazol-5-yl)-2-oxo-1-pyrrolidinyl]phenoxy}-3-{3-[4-(1,3,4-oxadiazol-2-yl)-2-oxo-1-pyrrolidinyl]phenoxy}naphthoquinone showed antifungal activity against Candida tenuis and Aspergillus niger at low concentrations, as determined by the serial dilution method. The substitution of the methoxy fragment by N-containing substituents in monophenoxy substituted naphthoquinones was found to decrease their activity against Mycobacterium luteum. Besides, introduction of the second phenoxy substituted fragment increased the antifungal activity against Candida tenuis and Aspergillus niger at lower concentrations.

Synthesis and Antimicrobial Activity of N-Substituted-β-amino Acid Derivatives Containing 2-Hydroxyphenyl, Benzo[b]phenoxazine and Quinoxaline Moieties

“…Hydrazones 5d–g were synthesized, under reflux conditions, by condensation of hydrazide 4 with different aromatic aldehydes in 2-propanol ( Scheme 1 ). Compounds 5d–g having an azomethine group appear as a mixture of E and Z isomers in solution [ 10 , 32 , 33 ] as it has been proven by their NMR spectra. For example, two doublets attributable to the CH 3 group protons at 1.18 ppm ( E isomer) and 1.22 ppm ( Z isomer), and two doublets of doublets attributable to the CH 2 group protons at 2.64 ppm and 3.08 ppm are observed in the 1 H-NMR spectrum for 5d .…”

“…Different 1,4-naphthoquinone derivatives have been reported as potent anticancer [ 5 , 6 ], antifungal [ 7 , 8 ], antibacterial [ 9 , 10 , 11 , 12 , 13 ], antiviral [ 14 , 15 ], and antiprotozoal therapeutic agents [ 16 ], as well as cholesterol acyltransferase inhibitors [ 17 ].…”

Synthesis and anticancer activity evaluation of naphthalene-substituted triazole spirodienones

“…The naphthalene ring widely exists in biologically active natural products [1], partaking in anti-inflammatory [2], antibacterial [3], antioxidant [4], and antifungal [5] properties in molecules containing the naphthalene moiety (Fig. 1A).…”

On the influence of small chemical changes upon the supramolecular association in substituted 2-(phenoxy)-1,4-naphthoquinones

“…Specifically, the structural skeleton of 2-(phenoxy)-1,4-naphthoquinone derivatives is found in a number of natural products that include Rubincolins [11], Newbouldiaquinones [12][13][14], Rubipodanones [15] and Lawsonol [16]; see Figure 1 for chemical structural formulae. The documented anti-trypanosomal [17][18][19][20][21][22][23][24] and anti-leishmanial activity [18] as well as the anti-tumour [15,23,[25][26][27][28][29] and anti-fungal activity [30][31][32] of natural and synthetic derivatives of 2-(phenoxy)-1,4naphthoquinones further highlights the significant chemical interest in this skeletal motif. As part of on-going studies [33][34][35][36][37][38] into the synthesis, structural characterisation and photochemistry of quinones, a series of new 2-(phenoxy)-1,4-naphthoquinone derivatives were prepared.…”