Some fused heterocyclic compounds as eukaryotic topoisomerase II inhibitors

Pınar, Aslı; Yurdakul, Pinar; Yildiz, İ̇lkay; Temiz-Arpacı, Özlem; Açan, N. Leyla; Aki-Sener, Esin; Yalçın, İsmail

doi:10.1016/j.bbrc.2004.03.093

Cited by 99 publications

(51 citation statements)

References 15 publications

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“…13 The compounds possess 3 different fused ring systems such as benzoxazole, benzimidazole, benzoxazin and an amide derivative (X12), which is the hydrolyzed form of the corresponding benzoxazole structure consisting of a cleavage of the oxazolo ring at the (CÀ ÀO) linkage that revealed at the phase I possible metabolites of benzoxazoles in the rabbit by mild hydrolysis. 34,35 In this study, we investigated the potential efficacy of these compounds in various human cancer cell lines that were derived from different tumor entities.…”

Section: Discussionmentioning

confidence: 99%

“…1) were synthesized as reported previously. 13 As control, the classical DNA topoisomerase II inhibitor etoposide (Bristol-Myers, Munich, Germany) was used.…”

Section: Dna Topoisomerase Ii-targeting Compoundsmentioning

confidence: 99%

“…Thus, we previously tested several derivatives of benzoxazoles, benzimidazoles, and related fused heterocyclic compounds with antimicrobial and antiviral activities for their inhibitory properties on eukaryotic Topo II in a cell-free system. 13 Since some of these compounds showed Topo II-inhibiting activity under cell-free conditions, in this study, we analyzed the potential antineoplastic activity of these agents in various human cancer cell lines established from different tumor entities and derived multidrug-resistant sublines with decreased Topo II expression. minimal essential vitamins and 20,000 kIE/l trasylol in a humidified atmosphere of 5% CO 2 at 37°C.…”

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confidence: 99%

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

Lage

Aki-Sener

Yalçın

2006

Intl Journal of Cancer

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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, drugsensitive cells merely the compounds BD3 and G35 showed efficacies, in terms of lM, 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. Key words: benzoxazole; benzimidazole; benzoxazin; DNA topisomerase II inhibitors; multidrug resistance DNA topoisomerases (Topo) 1 are enzymes that isomerise the tertiary structure of DNA without changing its primary structure. The high degree of conservation of these enzymes among prokaryotes and eukaryotes indicates an essential role in cell biology. Because its structure is a double helix, DNA is under tortional stress that results in multiplex twisting of the molecule. To be processed for replication or gene expression, the supercoiled DNA must become accessible to nucleic acids polymerases or components of the transcription machinery. This change requires relaxation and untangling of the intertwined DNA strands, which are the typical tasks of Topo.In humans, 2 classes of Topo are well characterized, type I and type II. Topo type II (Topo II) are useful as drug target, since they have an indispensable function in cell biology and they lack biological redundancy. Inhibitors of these enzymes have become central parts of both primary and adjuvant chemotherapy regimens in neoplastic diseases, and they probably will remain so for the foreseeable future. 2 Two Topo II isoforms, the 170 kDa Topo IIa and the 180 kDa Topo IIb, exist as homodimers and their amino acid sequences show homology at regions believed to be functionally significant (72% identical amino acid residues), 3 suggesting a comparable mode of action. The expression of Topo IIa varies during the cell cycle. It is low in quiescent cells, but maximal in the G 2 -M phase, whereas the expression level of Topo IIb remains constant througho...

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Section: Discussionmentioning

confidence: 99%

“…1) were synthesized as reported previously. 13 As control, the classical DNA topoisomerase II inhibitor etoposide (Bristol-Myers, Munich, Germany) was used.…”

Section: Dna Topoisomerase Ii-targeting Compoundsmentioning

confidence: 99%

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confidence: 99%

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

Lage

Aki-Sener

Yalçın

2006

Intl Journal of Cancer

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“…Among the tested compounds, 2-(phenoxymethyl)benzothiazole was found the most active derivative at a MIC value of 3.12 µg/ml against the tested S. aureus. 8 Moreover, the same compound was found very potent as an eukaryotic topoisomerase II inhibitor exhibiting a better inhibitor activity than reference drug [18][19][20] etoposide.…”

Section: Introductionmentioning

confidence: 90%

“…Hence, the development of novel, potent, and unique antibacterial agents is the preeminent way to overcome bacterial resistance and develop effective therapies. 5 The compounds possess benzothiazole nucleus in their structure are involved in research aimed at evaluating new chemotherapeutically active agents: such as antimicrobial [6][7][8][9] a topical carbonic anhydrase inhibitor, 10 a cyclooxygenase inhibitor, 11 antitubercular, 12,13 antinematode, 14 a dual inhibitor of thromboxane A 2 synthetase and 5-lipoxygenase 15 , a selective and reversible inhibitor of monoamine oxidase type A (MAO-A), 16 antiallergic, 17 multi-drug resistance cancer cell activities with inhibiting activity on eukaryotic topoisomerase II enzyme in cell-free system [18][19][20] and antitumor agents. [21][22][23] Currently, a new series of benzothiazoles have been synthesized as antitumor agents and showed potent inhibitory activity against human breast cancer cell lines in vitro and in vivo.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and In vitro Antimicrobial Activity of Novel 2-(4-(Substituted-carboxamido)benzyl / phenyl)benzothiazoles

et al. 2013

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Copper‐Catalyzed Efficient Multicomponent Reaction: Synthesis of Benzoxazoline‐Amidine Derivatives

Shang

et al. 2009

Adv Synth Catal

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Abstract:We have developed an efficient copper-catalyzed method for the synthesis of the benzoxazoline-amidine derivatives. The protocol uses inexpensive copper(I) iodide as the catalyst, and furnished the expected product in good to excellent yields by a three-component reaction of sulfonyl azides, terminal alkynes and Schiffs bases in terahydrofuran (THF) at room temperature for 8 h in the presence of triethylamine. This novel synthetic protocol is selective, efficient and general. A plausible mechanism for this process is proposed.

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Some fused heterocyclic compounds as eukaryotic topoisomerase II inhibitors

Cited by 99 publications

References 15 publications

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

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

Synthesis and In vitro Antimicrobial Activity of Novel 2-(4-(Substituted-carboxamido)benzyl / phenyl)benzothiazoles

Copper‐Catalyzed Efficient Multicomponent Reaction: Synthesis of Benzoxazoline‐Amidine Derivatives

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