1174416-71-7Relevant academic research and scientific papers
Discovery of pyrrolidine-2,3-diones as novel inhibitors of p. Aeruginosa pbp3
López-Pérez, Arancha,Freischem, Stefan,Grimm, Immanuel,Weiergr?ber, Oliver,Dingley, Andrew J.,López-Alberca, María Pascual,Waldmann, Herbert,Vollmer, Waldemar,Kumar, Kamal,Vuong, Cuong
, (2021/05/21)
The alarming threat of the spread of multidrug resistant bacteria currently leaves clinicians with very limited options to combat infections, especially those from Gram-negative bacteria. Hence, innovative strategies to deliver the next generation of antibacterials are urgently needed. Penicillin binding proteins (PBPs) are proven targets inhibited by β-lactam antibiotics. To discover novel, non-β-lactam inhibitors against PBP3 of Pseudomonas aeruginosa, we optimised a fluorescence assay based on a well-known thioester artificial substrate and performed a target screening using a focused protease-targeted library of 2455 compounds, which led to the identification of pyrrolidine-2,3-dione as a potential scaffold to inhibit the PBP3 target. Further chemical optimisation using a one-pot three-component reaction protocol delivered compounds with excellent target inhibition, initial antibacterial activities against P. aeruginosa and no apparent cytotoxicity. Our investigation revealed the key structural features; for instance, 3-hydroxyl group (R2) and a heteroaryl group (R1) appended to the N-pyrroldine-2,3-dione via methylene linker required for target inhibition. Overall, the discovery of the pyrrolidine-2,3-dione class of inhibitors of PBP3 brings opportunities to target multidrug-resistant bacterial strains and calls for further optimisation to improve antibacterial activity against P. aeruginosa.
Monocyclic β-lactam and unexpected oxazinone formation: synthesis, crystal structure, docking studies and antibacterial evaluation
Aneja, Babita,Irfan, Mohammad,Hassan, Md. Imtaiyaz,Prakash, Amresh,Yadava, Umesh,Daniliuc, Constantin G.,Zafaryab, Md.,Rizvi, M. Moshahid A.,Azam, Amir,Abid, Mohammad
, p. 834 - 852 (2016/07/07)
Novel monocyclic β-lactam derivatives bearing aryl, phenyl and heterocyclic rings were synthesized as possible antibacterial agents. Cyclization of imines (3h, 3t) with phenylacetic acid in the presence of phosphoryl chloride and triethyl amine did not afford the expected β-lactams. Instead, highly substituted 1,3-oxazin-4-ones (4h, 4t) were isolated as the only product and confirmed by single crystal X-ray analysis of 4t. The results of antibacterial activity showed that compound 4l exhibited considerable antibacterial activity with MIC and MBC values of 62.5 μg/mL against Klebsiella pneumoniae. Cytotoxicity assay on Chinese Hamster Ovary (CHO) cell line revealed non-cytotoxic behavior of compounds 4d, 4h, 4k and 4l up to 200 μg/mL conc. Molecular docking was performed for compound 4l with penicillin binding protein-5 to identify the nature of interactions. The results of both in silico and in vitro evaluation provide the basis for compound 4l to be carried as a potential lead molecule in the drug discovery pipeline against bacterial infections.
Synthesis and spectral studies on Ni(II) complexes involving N-furfuryl-N-substituted benzyldithiocarbamates and PPh3: Anagostic and C–H…π(chelate) interactions in (N-furfuryl-N-(4-fluorobenzyl)dithiocarbamato-S,S′)(thiocyanato-N)(tr
Sathiyaraj,Thirumaran,Ciattini, Samuele
, p. 1042 - 1050 (2016/07/06)
Twelve new nickel(II) complexes of functionalized dithiocarabamates [Ni(S2CNRR?)2](1-6) and [Ni(S2CNRR?)(NCS)(PPh3)](7-12) [where R=furfuryl; R?=2-hydroxy benzyl (1,7), 3-hydroxy benzyl (2,8), 4-hydroxy benzyl (3,9), 4-methoxy benzyl
Synthesis of 2-alkyl-1-aryl-1,2-dihydrochromeno[2,3-c]pyrrole-3,9-dione derivatives
Vydzhak,Panchishin, S. Ya.
experimental part, p. 2391 - 2397 (2009/05/30)
A preparative procedure for the synthesis of 2-alkyl-1-aryl-1,2- dihydrochromeno[2,3-c]pyrrole-3,9-diones from methyl 4-(o-hydroxyphenyl)-2,4- dioxobutanoate, aromatic aldehyde, and aliphatic amine is described.
