- In quest of small-molecules as potent non-competitive inhibitors against influenza
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A series of scaffolds namely aurones, 3-indolinones, 4-quinolones and cinnamic acid-piperazine hybrids, was designed, synthesized and investigated in vitro against influenza A/H1N1pdm09 virus. Designed molecules adopted different binding mode i.e., in 430-cavity of neuraminidase, unlike sialic acid and oseltamivir in molecular docking studies. All molecules reduced the viral titer and exhibited non-cytotoxicity along with cryo-protective property towards MDCK cells. Molecules (Z)-2-(3′-Chloro-benzylidene)-1,2-dihydro-indol-3-one (2f), (Z)-2-(4′-Chloro-benzylidene)-1,2-dihydro-indol-3-one (2g) and 2-(2′-Methoxy-phenyl)-1H-quinolin-4-one (3a) were the most interesting molecules identified in this research, endowed with robust potencies showing low-nanomolar EC50 values of 4.0 nM, 6.7 nM and 4.9 nM, respectively, compared to reference competitive and non-competitive inhibitors: oseltamivir (EC50 = 12.7 nM) and quercetin (EC50 = 0.56 μM), respectively. Besides, 2f, 2g and 3a exhibited good neuraminidase inhibitory activity in sub-micromolar range (IC50 = 0.52 μM, 3.5 μM, 1.3 μM respectively). Moreover, these molecules were determined as non-competitive inhibitors similar to reference non-competitive inhibitor quercetin unlike reference competitive inhibitor oseltamivir in kinetics studies.
- Malbari, Khushboo,Saha, Priyanka,Chawla-Sarkar, Mamta,Dutta, Shanta,Rai, Swita,Joshi, Mamata,Kanyalkar, Meena
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- An efficient and rapid intramolecular aza-Michael addition of 2′-aminochalcones using ionic liquids as recyclable reaction media
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A new, convenient, and efficient method for the intramolecular aza-Michael addition reaction of 2′-aminochalcones is developed using 1-n-butyl-3-methylimidazolium tetrafluoroborate as the solvent and catalyst. The ionic liquid is successfully regenerated and reused.
- Chelghoum,Bahnous,Bouraiou,Bouacida,Belfaitah
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experimental part
p. 4059 - 4061
(2012/08/28)
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