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Pregled bibliografske jedinice broj: 384615

Novel Derivatives of Pyridyl-Benzo[b]thiophene-2-carboxamides and Benzo[b]thieno[2, 3- c]naphthyridin-2-ones: Minor Structural Variations Provoke Major Differences of Antitumor Action Mechanisms


Ester, Katja; Hranjec, Marijana; Piantanida, Ivo; Ćaleta, Irena; Ivana, Jarak; Pavelić, Krešimir; Kralj, Marijeta; Karminski-Zamola, Grace
Novel Derivatives of Pyridyl-Benzo[b]thiophene-2-carboxamides and Benzo[b]thieno[2, 3- c]naphthyridin-2-ones: Minor Structural Variations Provoke Major Differences of Antitumor Action Mechanisms // Journal of Medicinal Chemistry, 52 (2009), 8; 2482-2492 (međunarodna recenzija, članak, znanstveni)


Naslov
Novel Derivatives of Pyridyl-Benzo[b]thiophene-2-carboxamides and Benzo[b]thieno[2, 3- c]naphthyridin-2-ones: Minor Structural Variations Provoke Major Differences of Antitumor Action Mechanisms

Autori
Ester, Katja ; Hranjec, Marijana ; Piantanida, Ivo ; Ćaleta, Irena ; Ivana, Jarak ; Pavelić, Krešimir ; Kralj, Marijeta ; Karminski-Zamola, Grace

Izvornik
Journal of Medicinal Chemistry (0022-2623) 52 (2009), 8; 2482-2492

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

Ključne riječi
Pyridyl-benzo b thiophene-2-carboxamides and benzo b thieno 2; 3-c naphthyridin-2-ones; DNA binding; anticancer activity; topoisomerase I inhibition; anti-tubulin activity; intercalators; minor groove

Sažetak
Novel cyano- and 2-imidazolinyl-substituted derivatives of pyridyl-benzo[b]thiophene-2- carboxamides 4, 5, 10-13 and benzo[b]thieno[2, 3-c]naphthyridin-2-ones 6, 7, 14-17 were prepared. All derivatives showed prominent antiproliferative effect. Extensive DNA binding studies and additional biological evaluations point to various modes/targets of action. The results strongly support intercalation into DNA as a dominant binding mode of fused analogues, which was substantiated using topoisomerase I inhibition assay. Most intriguingly, only minor structural difference between non-fused compounds 12 and 13 has strong impact on the interactions with DNA: while 13 binds within the DNA minor groove in the form of dimer, 12 does not form significant interactions with DNA. The assumption that severe mitotic impairment (G2/M phase arrest) induced by 12 could point to another important target – tubulin was confirmed by its obvious anti-tubulin activity observed in immunofluorescence assay, whereby treated cells showed disruption of microtubule formation comparable to the effect obtained by Paclitaxel, well-known tubulin antagonist chemotherapeutic.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Temeljne medicinske znanosti



POVEZANOST RADA


Projekt / tema
098-0982464-2393 - Molekularna obilježja miofibroblasta Dupuytrenove bolesti (Krešimir Pavelić, )
098-0982464-2514 - Uloga različitih mehanizama odgovora stanica na terapiju oštećenjem DNA (Marijeta Kralj, )
098-0982914-2918 - Dizajn, sinteza i ispitivanje interakcija malih molekula s DNA, RNA i proteinima (Ivo Piantanida, )
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