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Benzimidazole derivatives related to 2, 3-acrylonitriles, benzimidazo[1, 2-a]quinolines and fluorenes : Synthesis, Antitumor Evaluation in vitro and Crystal Structure Determination


Hranjec, Marijana; Pavlović, Gordana; Marjanović, Marko; Kralj, Marijeta; Karminski-Zamola, Grace
Benzimidazole derivatives related to 2, 3-acrylonitriles, benzimidazo[1, 2-a]quinolines and fluorenes : Synthesis, Antitumor Evaluation in vitro and Crystal Structure Determination // European journal of medicinal chemistry, 45 (2010), 2405-2417 doi:10.1016/j.ejmech.2010.02.022 (međunarodna recenzija, članak, znanstveni)


Naslov
Benzimidazole derivatives related to 2, 3-acrylonitriles, benzimidazo[1, 2-a]quinolines and fluorenes : Synthesis, Antitumor Evaluation in vitro and Crystal Structure Determination

Autori
Hranjec, Marijana ; Pavlović, Gordana ; Marjanović, Marko ; Kralj, Marijeta ; Karminski-Zamola, Grace

Izvornik
European journal of medicinal chemistry (0223-5234) 45 (2010); 2405-2417

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Benzimidazoles; acrylonitriles; benzimidazo[1; 2-a]quinoline-6-carbonitriles; fluorenes; antitumor evaluation; X-ray crystal structure determination

Sažetak
A synthesis and biological evaluation of new benzimidazole derivatives, related to 2, 3-disubstituted acrylonitriles, benzimidazo[1, 2-a]quinoline-6-carbonitriles and heteroaromatic fluorenes was described. The molecular and crystal structures of three compounds 4, 16 and 17 reveal that non-fused fluoro derivative, 4, deviates from planarity by 13.11(2), while fused methyl, 16, and fluoro, 17, derivatives are planar within 4 exhibiting a planar aromatic surface capable to intercalate into double-stranded DNA. The compound 4 exists as E-isomer. The crystal structures confirmed that hydrogen bonding patterns are characterized dominantly by the weak C-H•••N(F) bonds, except in the case of 4 where the presence of ethanol molecule of crystallization resulted in the N-H•••O and O-H•••N hydrogen bonds formation. In the crystal structures of 16 and 17 cyano group participates in hydrogen bonding formation, while in 4 this is not the case. All compounds, except 16 and 14 exerted pronounced antiproliferative activity on five tumor cell lines, whereby 2-benzimidazolyl-3-N-methylpyrolyl-acrylonitrile 13 and its fused analogue 23 exerted the highest activity on all cell lines (IC50 = 0.8 – 30 μM) and showed a special selectivity toward HeLa cells. There is no major difference in the biological activity between non-fused and fused analogues. Similarly, all compounds showed significant interaction with ct-DNA, supporting the fact that their antitumor activity could partially be the consequence of DNA-binding. The cyano moiety is important for the activity, but not the selectivity of tested compounds.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Temeljne medicinske znanosti



POVEZANOST RADA


Projekt / tema
098-0982464-2514 - Uloga različitih mehanizama odgovora stanica na terapiju oštećenjem DNA (Marijeta Kralj, )
098-1191344-2943 - Protein-ligand međudjelovanja na atomnoj razini (Marija Luić, )
125-0982464-1356 - Novi heterocikli kao antitumorski i antivirusni ("pametni") lijekovi (Marijana Hranjec, )

Ustanove
Institut "Ruđer Bošković", Zagreb,
Fakultet kemijskog inženjerstva i tehnologije, Zagreb

Časopis indeksira:


  • Current Contents Connect (CCC)
  • Web of Science Core Collection (WoSCC)
    • Science Citation Index Expanded (SCI-EXP)
    • SCI-EXP, SSCI i/ili A&HCI
  • Scopus
  • MEDLINE


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