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Pregled bibliografske jedinice broj: 221602

Structurally similar diazenes exhibit significantly different biological activity

Jakopec, Sanjica; Dubravčić, Klara; Brozović, Anamaria; Polanc, Slovenko; Osmak, Maja Osmak
Structurally similar diazenes exhibit significantly different biological activity // Cell biology and toxicology, 22 (2006), 1; 61-71 doi:10.1007/s10565-006-0023-2 (međunarodna recenzija, članak, znanstveni)

Structurally similar diazenes exhibit significantly different biological activity

Jakopec, Sanjica ; Dubravčić, Klara ; Brozović, Anamaria ; Polanc, Slovenko ; Osmak, Maja Osmak

Cell biology and toxicology (0742-2091) 22 (2006), 1; 61-71

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

Ključne riječi
Anti-cancer drugs; diazenes; cytotoxicity; cisplatin; doxorubicin; vincristine

We have synthesised previously various diazenecarboxamides (shortly diazenes) that were cytotoxic to several tumor cell lines. To increase their biological activity, the structure has been properly modified. In the present study we examined the effects of N1-phenyl-N2-(2-pyridinylmethyl)diazenedicarboxamide (RL-337) obtained from already examined cytotoxic compound N1-phenyl-N2-(2-pyridinyl)diazenecarboxamide JK-279, and compared them with those from diazene JK-279. Using a modified colorimetric MTT assay, the cytotoxicity of RL-337 was determined on human cervical carcinoma HeLa cells, glioblastoma A1235 cells, and prostate adenocarcinoma PC-3 cells. The possible synergistic effect of diazene RL-337 with cisplatin, doxorubicin and vincristine, and its influence on intracellular GSH content was examined on HeLa cells. Diazene RL-337 was cytotoxic against all three human tumor cell lines, being more cytotoxic to HeLa cells than diazene JK-279. Higher efficacy of RL-337 with regard to JK-279 can be connected with a higher basicity of the 2-picoline moiety, present in the former diazene, comparing with the pyridine fragment that is a part of the latter one. The diazene RL-337 acted synergistically with cisplatin, doxorubicine and vincristine (diazene JK-279 exhibited synergistic effect only with cisplatin). Glutathione (determined by Tietze’ s method) was not a target molecule of diazene RL-337 (but was for JK-279, as shown earlier). After just one hour treatment with diazene RL-337, the cells started to loose membrane integrity. There was no cleavage of caspase-3 in RL-337 treated samples, and the majority of cells died six hours after the treatment through necrosis (previously for diazene JK-279 apoptosis-like cell death was detected). Thus, although diazenes JK-279 and RL-337 are very similar in their structure, they exhibited largely different biological activity.

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Projekt / tema

Institut "Ruđer Bošković", Zagreb,
Klinički bolnički centar 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