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Mashevskaya, I. V.; Толмачева, И. А.; Voronova, E. V.; Одегова, Т. Ф.; Александрова, Г. А.; Goleneva, A. F.; Кольцова, С. В.; Масливец, А. Н.

doi:10.1023/a:1016064014955

Cited by 19 publications

(10 citation statements)

References 1 publication

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“…The compounds in Table 3 also inhibit the growth of E. coli M 17 and S. aureus P-209,20 and the SAR data presented here follows a similar trend to that reported previously in which halogen substituents lead to an increase in antibacterial activity. In addition, the MIC data also show that antibacterial activity is abolished by the introduction of a methyl group into the benzoxazine ring ( 15 and 18 ), as was observed for the methyl esters (Table 2, compounds 3 and 8 ).…”

supporting

confidence: 86%

“…In addition, the MIC values increased 5-fold for 14 and 16 , and 2.5-fold for 17 , (Table 3), compared to the analogous compounds in Table 2, suggesting that while a portion of their antibacterial activity could stem from an ability to inhibit MenB, there must be additional targets for these compounds in the cell. Many antibacterial benzoxazines previously reported also have bulky side chains and relatively poor activity against M. tuberculosis 19 as well as other bacteria 17, 20. Thus, again we would suggest that activity might be improved in the latter cases by reducing the size of the side chain.…”

mentioning

confidence: 76%

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Synthesis and SAR studies of 1,4-benzoxazine MenB inhibitors: Novel antibacterial agents against Mycobacterium tuberculosis

Liu

Zhang

et al. 2010

Bioorganic & Medicinal Chemistry Letters

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Menaquinone is an essential component of the electron transport chain in many pathogens and consequently enzymes in the menaquinone biosynthesis pathway are potential drug targets for the development of novel antibacterial agents. In order to identify leads that target MenB, the 1,4-dihydroxy-2-naphthoyl-CoA synthase from Mycobacterium tuberculosis, a high throughput screen was performed. Several 1,4-benzoxazines were identified in this screen and subsequent SAR studies resulted in the discovery of compounds with excellent antibacterial activity against M. tuberculosis H37Rv with MIC values as low as 0.6 µg/ml. The 1,4-benzoxazine scaffold is thus a promising foundation for the development of antitubercular agents.The emergence of multi-drug resistant (MDR-TB) and extensively-drug resistant (XDR-TB) strains of M. tuberculosis represents a severe threat to human health. Consequently, novel drugs are needed that are active against drug resistant bacteria and that also shorten the course of chemotherapy. In addition, novel agents are also required that are active against latent, nonreplicating populations of bacteria since M. tuberculosis can persist in this state for many years. 1-2 Since it seems likely that latent M. tuberculosis bacteria must respire in order to remain viable, compounds that target respiration are promising candidates for the development of drugs that are active against both replicating and non-replicating bacterial populations. Currently we are pursuing the hypothesis that menaquinone biosynthesis is essential for bacterial viability in vivo, and are actively engaged in identifying compounds that inhibit enzymes in this pathway.Menaquinone (vitamin K1) (Figure 1) is a polyisoprenylated naphthoquinone that shuttles electrons between membrane-bound protein complexes in the electron transport chain. In mammalian cells this function is performed by ubiquinone (Figure 1), and although

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supporting

confidence: 86%

mentioning

confidence: 76%

Synthesis and SAR studies of 1,4-benzoxazine MenB inhibitors: Novel antibacterial agents against Mycobacterium tuberculosis

Liu

Zhang

et al. 2010

Bioorganic & Medicinal Chemistry Letters

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“…Compounds 3 have described similar biological activities to the parent quinoxalin-2(1 H )-ones 1 . Mashevskaya et al reported about an antimicrobial activity for compound 6 at 1 mg/mL for S. aureus P-209 and E. coli M 17 strains [ 11 ]. Several recent studies have identified 3,4-dihydroquinoxalin-2(1 H )-ones 7–10 as hits for distinct biological targets [ 12 – 20 ], particularly antidiabetic 7 [ 20 ], anticancer 8 [ 18 ], anti-inflammatory 9 [ 16 ], and antibacterial 10 [ 19 ] ( Fig.…”

Section: Introductionmentioning

confidence: 99%

Switchable highly regioselective synthesis of 3,4-dihydroquinoxalin-2(1H)ones from o-phenylenediamines and aroylpyruvates

Dobiáš¹,

Ondruš²,

Addová³

et al. 2017

Beilstein J. Org. Chem.

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3-Acylmethylidene-3,4-dihydroquinoxalin-2(1H)-ones are compounds which possess a wide range of physical and pharmaceutical applications. These compounds can be easily prepared by cyclocondensation of o-phenylenediamines and aroylpyruvates. Unsymmetrically substituted o-phenylenediamines can be obtained form regioisomeric mixtures of 3,4-dihydroquinoxalin-2(1H)-ones. It is often quite difficult to get a pure regioisomer and determine its structure without controlling the reaction selectivity and exploitation of complex NMR techniques (HSQC, NOESY, HMBC). This article examines the regioselectivity of the cyclocondensation between six monosubstituted o-phenylenediamines (-OMe, -F, -Cl, -COOH, -CN, -NO2) and the derivatives of p-chlorobenzoylpyruvate (ester or acid) which we studied. Six regioisomeric 3,4-dihydroquinoxalin-2(1H)-one pairs were selectively prepared and characterised. Based on our experiences, a simplified methodology for determining the structure of the regioisomers was proposed. We developed two general and highly selective methodologies starting from the same o-phenylenediamines and activated 4-chlorobenzoylpyruvates (ester or acid) enabling switching of 3,4-dihydroquinoxalin-2(1H)-one regioselectivity in a predictable manner. For comparison, all regioselective cyclocondensations were performed with the same standardized conditions (DMF, rt, 3 days), differing only by the additives p-TsOH or HOBt/DIC (hydroxybenzotriazole/N,N’-diisopropylcarbodiimide). Both selected methods are simple, general and highly regioselective (72–97%). A mechanism for the regioselectivity was also proposed and discussed. This study can be used as a guide when choosing the most optimal reaction conditions for the synthesis of the desired 3,4-dihydroquinoxalin-2(1H)-one regioisomers with the best selectivity. The demonstrated methodologies in this article may also be applied to differently substituted 3,4-dihydroquinoxalin-2(1H)-ones in general, which could expand the synthetic impact of our results.

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“…Quinoxaline ring is a part of various antibiotics such as hinomycin, levomycin, and actinoleutin that are known to inhibit growth of Gram positive bacteria and are active against various transplantable tumours. [1][2][3][4][5][6][7] Quinoxaline derivatives have also been found to be associated with a wide variety of biological activities including antifungal, [8][9][10] antibacterial, [10][11][12][13][14] antitubercular, 8,9,[15][16][17][18] antiinflammatory agents. 19 Further, hydrazinoquinoxalines and their cyclic analogues have been reported as antimicrobial agents.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of 2-(3-methyl-2-oxoquinoxalin-1(2H)-yl)acetamide-based azetidinone derivatives as potent antibacterial and antifungal agents

Kumar¹,

Kumar²,

Drabu³

et al. 2013

J Chem Sci

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Twelve compounds belonging to series N -[3-chloro-2-oxo-4-(substituted)phenylazetidin-1-yl]-2-(3-methyl-2-oxoquinoxalin-1(2H )-yl)acetamide (5a-l) were synthesized. These compounds were evaluated for their in vitro antibacterial against E. coli, S. aureus, K. pneumoniae, P. aeruginosa and antifungal activity against C. albicans, A. niger and A. flavus by cup-plate method. Structures of all the newly synthesized compounds were confirmed by their spectral data interpretation. Compound 5g having p-dimethylaminophenyl group on 4-position of azetidinone ring attached to N-atom of acetamido group on 1-position of 3-methyl-1Hquinoxaline-2-one, was found to be active against all the bacterial and fungal strains under investigation.

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Cited by 19 publications

References 1 publication

Synthesis and SAR studies of 1,4-benzoxazine MenB inhibitors: Novel antibacterial agents against Mycobacterium tuberculosis

Synthesis and SAR studies of 1,4-benzoxazine MenB inhibitors: Novel antibacterial agents against Mycobacterium tuberculosis

Switchable highly regioselective synthesis of 3,4-dihydroquinoxalin-2(1H)ones from o-phenylenediamines and aroylpyruvates

Synthesis of 2-(3-methyl-2-oxoquinoxalin-1(2H)-yl)acetamide-based azetidinone derivatives as potent antibacterial and antifungal agents

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