Unique aminothiazolyl coumarins as potential DNA and membrane disruptors towards Enterococcus faecalis.

Aminothiazolyl coumarins as potentially new antimicrobial agents were designed and synthesized in an effort to overcome drug resistance. Biological activity assay revealed that some target compounds exhibited significantly inhibitory efficiencies toward bacteria and fungi including drug-resistant pathogens. Especially, aminothiazolyl 7-propyl coumarin 8b and 4-dichlorobenzyl derivative 11b exhibited bactericidal potential (MBC/MIC = 2) toward clinically drug-resistant Enterococcus faecalis with low cytotoxicity to human lung adenocarcinoma A549 cells, rapidly bactericidal effects and no obvious bacterial resistance development against E. faecalis. The preliminary antibacterial action mechanism studies suggested that compound 11b was able to disturb E. faecalis membrane effectively, and interact with bacterial DNA isolated from resistant E. faecalis through noncovalent bonds to cleave DNA, thus inhibiting the growth of E. faecalis strain. Further molecular modeling indicated that compounds 8b and 11b could bind with SER-1084 and ASP-1083 residues of gyrase-DNA complex through hydrogen bonds and hydrophobic interactions. Moreover, compound 11b showed low hemolysis and in vivo toxicity. These findings of aminothiazolyl coumarins as unique structural scaffolds might hold a large promise for the treatments of drug-resistant bacterial infection.

Selective α-oxidation of amides via visible-light-driven iron catalysis.

Hydroxyl radicals (˙OH) as one of the highly reactive species can react unselectively with a wide range of chemicals. The ˙OH radicals are typically generated under harsh conditions. Herein, we report hydroxyl radical-induced selective N-α C(sp3)-H bond oxidation of amides under greener and mild conditions via an Fe(NO3)3·9H2O catalyst inner sphere pathway upon irradiation with a 30 W blue LED light strip (λ = 455 nm) using NaBrO3 as the oxidant. This protocol exhibited high chemoselectivity and excellent functional group tolerance. A preliminary mechanism investigation demonstrated that the iron catalyst afforded hydroxyl radicals via the visible-light-induced homolysis (VLIH) of iron complexes followed by a hydrogen atom transfer (HAT) process to realize this transformation.

[Synthesis and antitumor activity of selenophosphocholine analogues containing tegafur].

AIM: To synthesize the selenophosphocholine analogues containing tegafur and test their antitumor activities. METHODS: The cyclic glyceroselenophospholopid conjugate of tegafur was synthesized by the reaction of hexaethylphosphorous triamide with N1-(2-furanidyl)-N3-(hydroxyalkyl)-5-fluyorouracil and 1-O-hexadecyl glycerol as well as selenium in one-pot. Cyclic glyceroselenophospholopid conjugate of tegafur reacted with triethylamine to give title compounds. RESULTS: Six new compounds have been synthesized. Their structures were confirmed by 1H NMR, 13P NMR and elemental analysis. Antitumor activity of the title compounds against PGA1 was tested. CONCLUSION: The reaction of triethylamine with cyclic glyceroselenophospholopid conjugate of tegafur very readily occurred, which was finished within 2 h at room temperature. The opening-ring products of trans isomers showed antimutor activity against human uriaryl bladder cancer cell more effective than that of the tegafur.