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High antineoplastic activity of new heterocyclic compounds in cancer cells with resistance against classical DNA topoisomerase II‐targeting drugs

Lage, Hermann ; Aki‐Sener, Esin ; Yalcin, Ismail

International journal of cancer, 2006-07, Vol.119 (1), p.213-220 [Periódico revisado por pares]

Hoboken: Wiley Subscription Services, Inc., A Wiley Company

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Título:
High antineoplastic activity of new heterocyclic compounds in cancer cells with resistance against classical DNA topoisomerase II‐targeting drugs
Autor: Lage, Hermann ; Aki‐Sener, Esin ; Yalcin, Ismail
Assuntos: Antineoplastic agents ; Antineoplastic Agents - chemistry ; Antineoplastic Agents - pharmacology ; benzimidazole ; benzoxazin ; benzoxazole ; Biological and medical sciences ; Blotting, Western ; Breast Neoplasms - drug therapy ; Cell Line, Tumor ; Cell Proliferation - drug effects ; Colonic Neoplasms - drug therapy ; DNA topisomerase II inhibitors ; DNA Topoisomerases, Type II - drug effects ; DNA Topoisomerases, Type II - metabolism ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Female ; Fibrosarcoma - drug therapy ; General aspects ; Heterocyclic Compounds - chemistry ; Heterocyclic Compounds - pharmacology ; Humans ; Male ; Medical sciences ; Melanoma - drug therapy ; multidrug resistance ; Neoplasms - drug therapy ; Neoplasms - enzymology ; Neoplasms - metabolism ; Pancreatic Neoplasms - drug therapy ; Pharmacology. Drug treatments ; Reverse Transcriptase Polymerase Chain Reaction ; Stomach Neoplasms - drug therapy ; Tumors ; Uterine Cervical Neoplasms - drug therapy
É parte de: International journal of cancer, 2006-07, Vol.119 (1), p.213-220
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Descrição: Twenty previously synthesized fused heterocyclic DNA‐topoisomerase II (Topo II)‐inhibiting compounds were investigated for their potential efficacy in various human cancer cell lines that were derived from different tumor entities. Moreover, different multidrug‐resistant variants of these cancer cell lines with decreased Topo II expression were investigated. In parental, drug‐sensitive cells merely the compounds BD3 and G35 showed efficacies, in terms of μM, which were similar to that of the classical Topo II inhibitor etoposide. On the other hand, most of the tested heterocyclic compounds were found more effective in drug‐resistant cells than in the parental, drug‐sensitive ones, and some of the compounds showed high antineoplastic efficacy in several drug‐resistant cell models. Compounds BD13, BD14 and BD16 exhibited high antineoplastic activities against the drug‐resistant sublines EPG85‐257RNOV and EPG85‐257RDB derived from gastric carcinoma, EPP85‐181RNOV and EPP85‐181RDB derived from pancreatic carcinoma, MCF‐7/Adr derived from breast cancer, D79/86RNOV derived from fibrosarcoma, and MeWoETO1 derived from melanoma. Furthermore, compound D23 was found highly efficient in the multidrug‐resistant variants HT‐29RNOV and HT‐29RDB derived from colon carcinoma, and compound D24 exhibited the highest antineoplastic activity among the tested compounds in the drug‐resistant subline MDA‐MB‐231ROV derived from breast cancer. In conclusion, compounds BD 13, BD 14, BD 16, D 23 and D 24 may be useful for the treatment of different multidrug‐resistant cancer cells with cross resistance against “classical” Topo II‐targeting drugs. © 2006 Wiley‐Liss, Inc.
Editor: Hoboken: Wiley Subscription Services, Inc., A Wiley Company
Idioma: Inglês

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High antineoplastic activity of new heterocyclic compounds in cancer cells with resistance against classical DNA topoisomerase II‐targeting drugs

Lage, Hermann ; Aki‐Sener, Esin ; Yalcin, Ismail

Hoboken: Wiley Subscription Services, Inc., A Wiley Company

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