Flavoenzyme-mediated reduction reactions and antitumor activity of nitrogen-containing tetracyclic ortho-quinone compounds and their nitrated derivatives

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dc.contributor.authorPečiukaitytė-Alksnė, Milda
dc.contributor.authorŠarlauskas, Jonas
dc.contributor.authorMisevičienė, Lina
dc.contributor.authorMarozienė, Audronė
dc.contributor.authorČėnas, Narimantas
dc.contributor.authorKrikštopaitis, Kastis
dc.contributor.authorStaniulytė, Zita
dc.contributor.authorAnusevičius, Žilvinas
dc.date.accessioned2017-10-26T14:05:05Z
dc.date.available2017-10-26T14:05:05Z
dc.date.issued2017-05-11
dc.description.abstractNitrogen-based tetracyclic ortho-quinones (naphtho[1'2':4.5]imidazo[1,2-a]pyridine-5,6-diones, NPDOs) and their nitro-substituted derivatives (nitro-(P)NPDOs) were obtained by condensation of substituted 2,3-dichloro- 1,4-naphthoquinones with 2-amino-pyridine and -pyrimidine and nitration at an elevated temperature. The structural features of the compounds as well as their global and regional electrophilic potency were characterized by means of DFT computation. The compounds were highly reactive substrates of single- and two-electron (hydride)- transferring P-450R (CPR; EC 1.6.2.4) and NQO-1 (DTD; EC 1.6.99.2), respectively, concomitantly producing reactive oxygen species. Their catalytic efficiency defined in terms of the apparent second-order rate constant (kcat/KM (Q)) values in P-450R- and NQO-1-mediated reactions varied in the range of 3-6 × 107 M-1 s-1 and 1.6-7.4 × 108 M-1 s-1, respectively. The cytotoxic activities of the compounds on tumor cell lines followed the concentration-dependent manner exhibiting relatively high cytotoxic potency against breast cancer MCF-7, with CL50 values of 0.08-2.02 µM L-1 and lower potency against lung cancer A-549 (CL50 = 0.28-7.66 µM L-1). 3-nitro-pyrimidino- NPDO quinone was the most active compound against MCF-7 with CL50 of 0.08 ± 0.01 µM L-1 (0.02 µg mL-1)) which was followed by 3-nitro-NPDO with CL50 of 0.12 ± 0.03 µM L-1 (0.035 µg mL-1)) and 0.28 ± 0.08 µM L-1 (0.08 µg mL-1) on A-549 and MCF-7 cells, respectively, while 1- and 4-nitro-quinoidals produced the least cyto- or cells quantified by AO/EB staining showed that the cell death induced by the compounds occurs primarily through apoptosis.en
dc.identifier.issn1611-2156
dc.identifier.urihttp://hdl.handle.net/2003/36155
dc.identifier.urihttp://dx.doi.org/10.17877/DE290R-18171
dc.language.isoen
dc.relation.ispartofseriesEXCLI Journal;Vol. 16 2017
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectheterocycle quinonesen
dc.subjectortho-quinonesen
dc.subjectenzymatic reactivityen
dc.subjectantitumor activityen
dc.subjectapoptosisen
dc.subjectDFT computationen
dc.subject.ddc610
dc.titleFlavoenzyme-mediated reduction reactions and antitumor activity of nitrogen-containing tetracyclic ortho-quinone compounds and their nitrated derivativesen
dc.typeText
dc.type.publicationtypearticle
dcterms.accessRightsopen access
eldorado.dnb.zdberstkatid2132560-1
eldorado.secondarypublicationtrue

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