Antiproliferative activity of new benzimidazole derivatives

• Autorzy: Blaszczak-Swiatkiewicz K. , Olszewska P. , Mikiciuk-Olasik E.
• Języki publikacji: EN

Abstrakty

EN

A series of new benzimidazole derivatives were synthesized and tested in vitro for possible anticancer activity. Their effect of proliferation into selected tumor cell lines at normoxia and hypoxia conditions was determined by WST-1 test. Additionally, apoptosis test (caspase 3/7 assay) was used to check the mode caused by the agents of cell death. Four of the examined compounds (7, 8, 13, 11) showed a very good antiproliferative effect and three of them were specific for hypoxia conditions (8, 14, 11). Compound 8 was the most cytotoxic against human lung adenocarcinoma A549 cells at hypoxic conditions. Hypoxia/ normoxia cytotoxic coefficient of compound 14 (4.75) is close to hypoxia/normoxia cytotoxic coefficient of tirapazamine (5.59) - a reference compound in our experiments and this parameter locates it between mitomycin C and 2-nitroimidazole (misonidazole). Screening test of caspase-dependent apoptosis proved that exposure to A549 cells of compounds 7-8 and 13-14 for 48 h promote apoptotic cell death. These results supplement our earlier study of the activity of new potentialy cytotoxic heterocyclic compounds against selected tumor cells.

Słowa kluczowe

EN

antiproliferative activity; benzimidazole derivative; anticancer activity; apoptosis; benzimidazole; hypoxia; nitrobenzimidazole

• Wydawca: -
• Czasopismo: Acta Biochimica Polonica
• Rocznik: 2013
• Tom: 60
• Numer: 3
• Opis fizyczny: p.427-433,fig.,ref.

Twórcy

autor

Blaszczak-Swiatkiewicz K.

• Department of Pharmaceutical Chemistry and Drug Analysis, Medical University, Lodz, Poland

autor

Olszewska P.

• Department of Pharmaceutical Chemistry and Drug Analysis, Medical University, Lodz, Poland

autor

Mikiciuk-Olasik E.

• Department of Pharmaceutical Chemistry and Drug Analysis, Medical University, Lodz, Poland

Bibliografia

• Albertella MR, Loadman PM, Jones PH (2008) Hypoxia-selective targeting by the bioreductive prodrug AQ4N in patients with solid tumors: results of a phase I study. Clin Cancer Res 14: 1096-1104. 
• Alpan AS, Gunes HS, Topcu Z (2007) 1H-Benzimidazole derivatives as mammalian DNA topoisomerase I inhibitors, Acta Biochim Pol 54: 561-565. 
• Alpan AS, Zupko SZ, Coban G, Rethy B, Gunes HS, Topcu Z (2009) Biological activity of bis-benzimidazole derivatives on DNA topoisomerase I and HeLa, MCF7 and A431 cells. J Enzyme Inhibit Medi Chem 24: 844-849. 
• Alper S, Arpaci OT, Aki ES, Yalcin I (2003) Some new bi- and ter-benzimidazole derivatives as topoisomerase Inhibitors. Farmaco 58: 497-507. 
• Błaszczak-Świątkiewicz K, Mikiciuk-Olasik E (2008) Role of hipoxia in advances in new anticancer diagnostics and therapy. Wiadomości Chemiczne 62: 11-12, 1065-1089 (in Polish).
• Błaszczak-Świątkiewicz K, Mirowski M, Kaplińska K, Kruszyński R, Trzęsowska-Kruszyńska A, Mikiciuk-Olasik E (2012) New benzimidazole derivatives with potential cytotoxic activity - study of their stability by RP-HPLC. Acta Biochim Pol 59: 279-288. 
• Coban G, Zencir S, Zupko I, Rethy B, Gunes HS, Topcu Z (2009) Synthesis and biological activity evaluation of 1H-benzimidazoles via mammalian DNA topoisomerase I and cytostaticity assays. Eur J Med Chem 44: 2280-2285. 
• Forsythe JA, Jiang BH, Iyer NV, Agani F, Leung SW, Koos RD, Semenza GL (1996) Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1. Mol Cell Biol 16: 4604-4613. 
• Jerchel D, Fischer H, Kracht M (1952) Zur darstellung der benzimidazole. Justus Liebigs Annalen der Chemie 575: 162.
• Kim JW, Tchernyshyov I, Semenza GL (2006) HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptoation to hypoxia. Cell Metabolism 3: 177-185. 
• Kurtzberg LS, Roth S, Krumbholz R, et al. (2001) Genz-644282, A Novel Non-Camptothecin Topoisomerase I Inhibitor for Cancer Treatment. Clin Cancer Res 17: 2777-2787. 
• Łazowski J (1999) Clinical pharmacology of irinotecan. Farmacja Polska 55: 28-34 (in Polish).
• McKeown SR, Cowen RL, Williams KJ (2007) Bioreductive drugs: from concept to clinic. Clin Oncol (R Coll Radiol) 19: 427-442. 
• Meng L, Liao Z, Pommier Y (2003) Non-camptothecin DNA topoisomerase i inhibitors in cancer therapy. Curr Topics Med Chem 3: 305-320. 
• Mikiciuk-Olasik E, Błaszczak-Świątkiewicz K, Żurek E, Krajewska U, Różalski M, Kruszyński R, Bartczak TJ (2004) New derivatives of quinazoline and 1,2-dihydroquinazoline N3-oxide with expected antitumour acivity. Archiv der Pharmazie 337: 239-246. 
• Oksuzoglu E, Tekiner-Gulbas B, Alper S, Temiz-Arpaci O, Ertan T, Yildiz I, Diril N, Sener-Aki E, Yalcin I (2008) Some benzoxazoles and benzimidazoles as DNA topoisomerase I and II inhibitors. J Enzyme Inhibit Med Chem 23: 37-42. 
• Omyła-Staszewska J, Deptała A (2003) Topoizomerase I inhibitors - a uniqe class of anticancer drugs. Współczesna Onkolgia 7: 45-53 (in Polish).
• Panieres GC, Bonifas IA, Guadalupe JC, Lopez JE, Guadalupe G, Alvarez CT (2000) Synthesis of benzimidazoles in dry medium. Synthetic Commun 30: 2195.
• Preston PN (1974) Synthesis, reactions and spectroscopic properties of benzimidazoles. Chem Rev 74: 279-314.
• Pommier Y (1999) Topoisomerase I inhibitors: camptothecins and beyond. Nat Rev Cancer 6: 789-802. 
• Semenza GL (1999) Regulation of mammalian O2 homeostasis by hypoxia-inducible factor 1. Annu Rev Cell Dev Biol 15: 551-578. 
• Singh M, Tandon V (2011) Synthesis and biological activity of novel inhibitors of topoisomerase I: 2-Aryl-substituted 2-bis-1H-benzimidazoles. Eur J Med Chem 46: 659-669. 
• Vaupel P (2004) The role of hypoxia-induced factors in tumor progression. Oncologist 9: 10-17. 
• Wu N, Wu XW, Agama K, Pommier Y, Du J, Li D, Gu LQ, Huang ZS, An LK (2010) A novel DNA Topoisomerase I inhibitor with different mechanism from camptothecin induces G2/M phase cell cycle arrest to K562 cells. Biochemistry 49: 10131-10136.