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Quinoxalin-2(1H)-one based design and synthesis produced several series of aldose reductase (ALR2) inhibitor candidates. In particular, phenolic structure was installed in the compounds for the combination of antioxidant activity and strengthening the ability to fight against diabetic complications. Most of the series 6 showed potent and selective effects on ALR2 inhibition with IC50 values in the range of 0.032-0.468 μM, and 2-(3-(2,4-dihydroxyphenyl)-7-fluoro-2-oxoquinoxalin-1(2H)-yl)acetic acid (6e) was the most active. More significantly, most of the series 8 revealed not only good activity in the ALR2 inhibition but also potent antioxidant activity, and 2-(3-(3-methoxy-4-hydroxystyryl)-2-oxoquinoxalin-1(2H)-yl)acetic acid (8d) was even as strong as the well-known antioxidant Trolox at a concentration of 100 μM, verifying the C3 p-hydroxystyryl side chain as the key structure for alleviating oxidative stress. These results therefore suggest an achievement of multifunctional ALR2 inhibitors having both potency for ALR2 inhibition and as antioxidants.

Novel quinoxalinone derivatives were synthesized and tested for their inhibitory activity against aldose reductase. Among them, N1-acetate derivatives had significant activity in a range of IC50 values from low micromolar to submicromolar, and compound 15a bearing a C3-phenethyl side chain was identified as the most potent inhibitor with an IC50 value of 0.143 μM. The structure-activity studies suggested that both C3-phenethyl and C6-NO2 groups play an important role in enhancing the activity and selectivity of the quinoxalinone based inhibitors., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

A novel, non-acid series of nitroquinoxalinone derivatives was synthesized and tested for their inhibitory activity against aldose reductase as targeting enzyme. All active compounds displayed an 8-nitro group, and showed significant activity in IC50 values ranging from 1.54 to 18.17 μM. Among them 6,7-dichloro-5,8-dinitro-3-phenoxyquinoxalin-2(1H)-one (7e), exhibited the strongest aldose reductase activity with an IC50 value of 1.54 μM and a good SAR (structure-activity relationship) profile., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

A novel and facile synthesis of quinoxalinone derivatives was developed in which a wide range of 3-chloroquinoxalin-2(1H)-ones as key intermediates can be generated chemo- and regioselectively in good yields from corresponding quinoxaline-2,3(1H,4H)-diones. This new protocol is arguably superior, as it allows the design and preparation of a variety of bioactive quinoxaline-based compounds, which are particularly effective in the treatment of diabetes and its complications. Through this procedure, a new class of quinoxalinone-based aldose reductase inhibitors were synthesized successfully. Most of the inhibitors, with an N1-acetic acid head group and a substituted C3-phenoxy side chain, proved to be potent and selective. Their IC(50) values ranged from 11.4 to 74.8 nM. Among them, 2-(3-(4-bromophenoxy)-7-fluoro-2-oxoquinoxalin-1(2H)-yl)acetic acid and 2-(6-bromo-3-(4-bromophenoxy)-2-oxoquinoxalin-1(2H)-yl)acetic acid were the most active. Structure-activity relationship and molecular docking studies highlighted the importance of the ether spacer in the C3-phenoxy side chains, and provided clear guidance on the contribution of substitutions both at the core structure and the side chain to activity., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

• The Quinoxaline-based Schiff base serves as effective colorimetric chemosensor for CN͞ ion sensing. • By using 1H NMR and DFT calculations, the hypothesized sensing mechanism of HG-1 towards CN͞ ion was verified. • A combinatorial logic gate circuit was built using HG-1's reversibility towards CN͞ ion and MeOH. • The HG-1 was used to detect CN͞ ion in test strips. Cyanide ion is very toxic for both environment and human being, so it is necessary to design a chemosensor for cyanide ion detection. For this purpose, Two novel chemosensors based on 3-hydrazinylquinoxalin-2(1H)-one and aromatic aldehydes were synthesized named as (E)-3-(2-(5-fluoro-2-oxo-1H-indol-3(2H,3aH,7aH)-ylidene)hydrazinyl)quinoxalin-2(1H)-one (HG-1) and (Z)-3-(2-(4-morpholinobenzylidene)hydrazinyl)quinoxalin-2(1H)-one (HG-2) for selective detection of cyanide ion. The structural characterization was done by analytical techniques such as UV/Visible, FTIR, 1HNMR, 13CNMR, EI-MS and UPLC. Further confirmation of chemosensor sensing was done by DFT and TDDFT calculations with B3LYP/6-31G (d, p) method by performing QTAIM, FMO, UV/Vis and global reactivity parameters (GRPs) elucidation. The binding constant was calculated as 4.14 × 106 M−1 and detection limit was calculated as 21 × 10−6 M. In the presence of CN͞ ion, chemosensor HG-1 generated a noticeable color change from light yellow to orange. To build a combinatorial logic circuit gate, the reverse reaction of chemosensor with methanol is useful. Overall results shows that chemosensor HG-1 has greater selectivity for CN͞ ion than HG-2. Test strips were made for CN͞ ion detection. A simple quinoxaline based Schiff bases have been created. The chemosensor HG-1 has a rapid response time, good sensitivity, and high selectivity towards CN͞ ions. The chemosensor served analytical purposes well. [Display omitted] [ABSTRACT FROM AUTHOR]