C-7 modified flavonoids as novel tyrosyl-tRNA synthetase inhibitors

Abstract

Twenty C-7 modified flavonoids were designed and synthesized. Biological evaluation in vitro indicated that compounds generated by SYBYL-X with high scores also showed good inhibitory activities against TyrRS.Compounds containing the nargenin core exhibit better enzyme inhibitory activities than other flavonoid cores, with (S)-5-hydroxy-4 0 -hydroxy-7-(2-morpholino-2-oxoethoxy)-2,3-dihydroflavone (b1) being the most active (IC 50 ¼ 0.10 AE 0.01 mM) in all assayed compounds. All compounds were also assayed for antimicrobial activities against Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa, and b1 also displayed excellent activity, showing 6-fold more potent than the marketed antibiotic ciprofloxacin. In comparison with Gram-positive organism, all these derivatives exhibited better activity against Gram-negative organism, and did not displayed significant differences between the two assayed Gram-negative strains (E. coli ATCC 8739 and P. aeruginosa ATCC 9027). Fig. 2 Scaffold hopping and library design. Superpositions of tyrosyl adenylate (white) with a 7-O-graft flavonoid derivative (light purple) and 5-O-graft flavonoid derivative (light brown) generated by Surflex Sim suite of SYBYL-X 2.1.1. 6194 | RSC Adv., 2017, 7, 6193-6201 This journal is

Antibacterial activity of flavonoids and their structure–activity relationship: An update review

“…aureus (sixfold more potent than the marketed antibiotic ciprofloxacin). The result showed that R4 (N‐containing heterocyclic compounds) were more active than alkyl or aromatic amino containing analogues at the C‐7 side chain (Xiao et al, )…”

“…coli , and this compound indicated complete inhibition of FabI activity at the concentration of 100 μM (Allison et al, ). In 2017, the enzyme assays of 20 C‐7 modified flavonoids for inhibition tyrosyl‐tRNA synthetase in Gram‐positive and Gram‐negative organism revealed that ( S )‐5‐hydroxy‐40‐hydroxy‐7‐(2‐morpholino‐2‐oxoethoxy)‐2,3‐dihydroflavone ( 160 ) exhibited better activity against Gram‐negative organism with IC 50 lower than 1 mM (Xiao et al, ).…”

The Interactions between Polyphenols and Microorganisms, Especially Gut Microbiota

“…Flavones form a complex with cell wall components and consequently inhibit further adhesions and microbial growth as well. The inhibition of bacterial enzymes (such as tyrosyl-tRNA synthetase) was observed for C-7-modified flavonoids containing the naringenin (81) core [ 147 ]. It was also demonstrated that they were also inhibitors of S. aureus , E. coli , and Pseudomonas aeruginosa growth.…”

In situ polymerization of graphene-polyaniline@polyimide composite films with high EMI shielding and electrical properties

“…S1(b) in ESI, † aer 8 hours of standing, Gr sheets aggregate partly in NMP, but, Gr-PANI 10:1 composite ller shows excellent dispersibility due to the p-p non-covalent interactions between Gr and PANI, indicating that the PANI can avoid the agglomeration of Gr sheets in the organic solvent. 18 The SEM morphologies of Gr, Gr-PANI 10:1 , PI and 40%Gr-PANI 10:1 @PI are shown in Fig. 2.…”