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Antitumor potential of crown ethers: structure activity relationships, cell cycle disturbances and cell death studies of a series of ionophores


Marjanović, Marko; Kralj, Marijeta; Supek, Fran; Frkanec, Leo; Piantanida, Ivo; Šmuc, Tomislav; Tušek-Božić, Ljerka
Antitumor potential of crown ethers: structure activity relationships, cell cycle disturbances and cell death studies of a series of ionophores // Journal of medicinal chemistry, 50 (2007), 5; 1007-1018 doi:10.1021/jm061162u (međunarodna recenzija, članak, znanstveni)


Naslov
Antitumor potential of crown ethers: structure activity relationships, cell cycle disturbances and cell death studies of a series of ionophores

Autori
Marjanović, Marko ; Kralj, Marijeta ; Supek, Fran ; Frkanec, Leo ; Piantanida, Ivo ; Šmuc, Tomislav ; Tušek-Božić, Ljerka

Izvornik
Journal of medicinal chemistry (0022-2623) 50 (2007), 5; 1007-1018

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

Ključne riječi
Crown ethers; ionophores; antitumor; cell cycle; apoptosis; potassium transport

Sažetak
The present paper demonstrates the antiproliferative ability and structure-activity relationships (SAR) of fourteen crown and aza-crown ether analogues on five tumor-cell types. The most active compounds were di-tert-butyldicyclohexano-18-crown-6 (3), which exhibited cytotoxicity in the submicromolar range and di-tert-butyldibenzo-18-crown-6 (5) (IC50 values of ≈ 2 µ ; ; ; ; ; M). Besides, 3 and 5 induced marked influence on the cell cycle phase distribution - strong G1 arrest, followed by the induction of apoptosis. A computational SAR modeling effort offers insights into possible mechanisms of crown ether biological activity, presumably involving penetration into cell membranes, and points out structural features of molecules important for this activity. The results reveal that crown ethers possess marked tumor-cell growth inhibitory activity the extent of which depends on the characteristics of the hydrophilic macrocylic cavity and the hydrophobic ring surrounding. Our work supports the hypothesis that crown ether compounds inhibit tumor cell growth by disrupting potassium ion homeostasis, which in turn leads to cell cycle perturbations and apoptosis.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Biologija, Temeljne medicinske znanosti



POVEZANOST RADA


Projekt / tema
098-0982464-2514 - Uloga različitih mehanizama odgovora stanica na terapiju oštećenjem DNA (Marijeta Kralj, )
098-0982904-2912 - Samo-udruživanje u gelovima i sinteza funkcionalnih hibridnih materijala (Leo Frkanec, )
098-0982914-2918 - Dizajn, sinteza i ispitivanje interakcija malih molekula s DNA, RNA i proteinima (Ivo Piantanida, )
098-0982915-2950 - Dizajn, sinteza i svojstva organskih liganada i njihovih metalnih kompleksa (Manda Ćurić, )

Ustanove
Institut "Ruđer Bošković", 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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