Antibacterial and antifungal activities of 2,3-pyrrolidinedione derivatives against oral pathogens

Abstract

Among the novel approaches applied to antimicrobial drug development, natural product-inspired synthesis plays a major role, by providing biologically validated starting points. Tetramic acids, a class of natural products containing a 2,4-pyrrolidinedione ring system, have attracted considerable attention for their antibacterial, antiviral, antifungal and anticancer activities. On the contrary, compounds with a 2,3-pyrrolidinedione skeleton have been considerably less investigated. In this work, we established chemical routes to the substituted 2,3-pyrrolidinedione core, which enabled the introduction of a wide range of diversity. In the perspective of a potential application for oral healthcare, a number of analogues with various substituents on the 2,3-pyrrolidinedione core were investigated for their antimicrobial and antifungal activities. The most promising compound showed a significant antimicrobial activity on Streptococcus mutans and Candida albicans, comparable to that of chlorhexidine, the gold standard in oral healthcare.

Total synthesis of leopolic acid A, a natural 2,3-pyrrolidinedione with antimicrobial activity

“…We chose the p -methoxybenzyl (PMB) protecting group for the amine, because of its facile cleavage with cerium ammonium nitrate (CAN) or 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ). Thus, 2,3-pyrrolidinedione 3 was obtained by the reaction of ethyl acrylate with p -methoxybenzylamine, followed by treatment with diethyl oxalate ( Scheme 1 ) [ 12 ]. On the basis of NMR data, the compound exists as an enol tautomer (see Supporting Information File 1 ).…”

“…The reduction of 4 with DIBAL-H gave the corresponding primary alcohol, which was converted into bromide 5 by Appel reaction with PPh 3 and CBr 4 . The phosphonium salt obtained from this bromide was subjected to a Wittig reaction with nonanal, to afford compound 6 [ 12 ].…”

Amination of 5-Spiro-Substituted 3-Hydroxy-1,5-dihydro-2H-pyrrol-2-ones

“…The 3-hydroxy-1,5-dihydro-2 H -pyrrol-2-one (HDP) motif ( Figure 1 ) is a valuable scaffold in drug discovery. Inhibitors of p53–MDM2 protein–protein interaction [ 1 , 2 ], inhibitors of HIV integrase [ 3 , 4 ], antibacterial agents against methicillin-resistant Staphylococcus aureus [ 5 ], dengue virus helicase inhibitors [ 6 ], P2X3 receptor antagonists [ 7 ], and other potential pharmaceuticals [ 8 , 9 ] have been developed on its basis.…”

Antifungal effect of 7-hydroxycitronellal against C. Tropicalis strains: an in vitro approach

“…Oral candidiasis is the most common human fungal infection, is characterized by excessive growth of the Candida species in the superficial oral mucosa epithelium (MELKOUMOV et al, 2013;DHAVAN et al, 2016).…”