Synthesis and antiproliferative activity of indolizinophthalazine-5,12-dione derivatives, DNA topoisomerase IB inhibitors

Shen, De-Qing; Wu, Zuping; Wu, Xi-Wei; An, Zeng‐Yun; Bu, Xiang-Zhang; Gu, Lian‐Quan; Huang, Zhi‐Shu; An, Lin‐Kun

doi:10.1016/j.ejmech.2010.05.048

Cited by 19 publications

(4 citation statements)

References 15 publications

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“…In addition to the classical Fischer indole synthesis, a large number of methods are known for the synthesis of substituted indoles. , Despite these advances, the development of a modular and regiospecific approach to substituted indoles is of considerable interest. Herein, we disclose a regiospecific synthesis of indole derivatives, which are used as intermediates for the construction of indole-fused saturated and unsaturated pyrido[1,2- a ]indoles , and carbazoles (Scheme ). ,− Owing to their prevalence in natural products and biologically active molecules, , the development of practical and scalable synthetic approaches for indole-fused heterocyclic scaffolds is desirable.…”

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confidence: 99%

“…Herein, we disclose a regiospecific synthesis of indole derivatives, which are used as intermediates for the construction of indole-fused saturated and unsaturated pyrido[1,2- a ]indoles , and carbazoles (Scheme ). ,− Owing to their prevalence in natural products and biologically active molecules, , the development of practical and scalable synthetic approaches for indole-fused heterocyclic scaffolds is desirable.…”

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confidence: 99%

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Divergent and Orthogonal Approach to Carbazoles and Pyridoindoles from Oxindoles via Indole Intermediates

et al. 2018

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The previously unexplored Grignard addition to oxindoles provides a regiospecific approach to 2- and 2,3-disubstituted indole derivatives in high yields via a one-pot aromatization driven dehydration pathway. This method allows a convenient preparation of diallyl indoles that are used as ring-closing metathesis (RCM) precursors for the orthogonal synthesis of pyrido[1,2- a]indoles and carbazoles. The synthetic utility of this method is illustrated by the synthesis of a microtubulin inhibitor and naturally occurring carbazole alkaloids.

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confidence: 99%

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confidence: 99%

Divergent and Orthogonal Approach to Carbazoles and Pyridoindoles from Oxindoles via Indole Intermediates

et al. 2018

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“…Structure activity relationships (SAR) evaluation indicated that the nitrogen atomin the A ring played an important role for cytotoxicity. N,N-syn isomer exhibited higher cytotoxicity and Top1 inhibitory activity than N,N-trans isomer or the corresponding derivatives with two nitrogen atoms in the A ring, such as indolizinophthalazinediones and indolizinoquinoxalinediones [10,11]. This led us to propose that the aminoalkyl side chain enhanced the cytotoxicity and Top1 inhibitory activity of the parent molecule possibly because the cationic side chain under physiological condition could improve cellular uptake and interactions with the Top1-DNA complex [12-15].…”

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confidence: 99%

Synthesis and biological evaluation of 6-substituted indolizinoquinolinediones as catalytic DNA topoisomerase I inhibitors

Zhang

et al. 2015

European Journal of Medicinal Chemistry

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In our previous work, indolizinoquinolinedione derivative 1 was identified as a Top1 catalytic inhibitor. Herein, a series of 6-substituted indolizinoquinolinedione derivatives were synthesized through modification of the parent compound 1. Top1 cleavage and relaxation assays indicate that none of these novel compounds act as classical Top1 poison, and that the compounds with alkylamino terminus at C-6 side chain, including 8, 11–16, 18–21, 25, 26 and 28–30, are the most potent Top1 catalytic inhibitors. Top1-mediated unwinding assay demonstrated that 14, 22 and 26 were Top1 catalytic inhibitors without Top1-mediated unwinding effect. Moreover, MTT results showed that compounds 26, 28–30 exhibit significant cytotoxicity against human leukemia HL-60 cells, and that compound 26 exerts potent cytotoxicity against A549 lung cancer cells at nanomolar range.

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“…8) exhibited well consistent antiproliferative and topo I inhibitory activites. This study indicated that the indolizinoquinoline-5,12-dione structure might serve as a potential pharmacophore for the design of anticancer chemical entities, and topo I might be a biological target [61].…”

Section: Dna Topoisomerasesmentioning

confidence: 84%

Natural Products, Synthetic and Non-Nucleoside Compounds as Inhibitors of Enzymes Related to DNA: Update 2013

Pungitore

2014

CEI

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This review article tries to be an update of 2008 Pungitore's review. Again, this paper tries to summarize the investigation about natural products, synthetic and non-nucleoside compounds with the ability to inhibit enzymes that play a crucial role in DNA metabolism such as replication, transcription, retro-transcription, recombination, and chromosome segregation during mitosis. The focus is placed on DNA polymerases, topoisomerases and reverse transcriptase inhibitors because most of the literature emphasized on their inhibitory activity. A great diversity of chemical compounds encompassing triterpenes, flavonoids, chromones, lipids, iridoids, phytosterols, coumarins, anthracyclines, quinones, protoberberines, tannins, lignans, acetogenins, benzimidazoles and other natural products, produced by different species of organisms, have inhibitory activities against enzymes related to DNA metabolism allowing these enzymes to arise as important molecular targets for cancer and AIDS research.

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Synthesis and antiproliferative activity of indolizinophthalazine-5,12-dione derivatives, DNA topoisomerase IB inhibitors

Cited by 19 publications

References 15 publications

Divergent and Orthogonal Approach to Carbazoles and Pyridoindoles from Oxindoles via Indole Intermediates

Divergent and Orthogonal Approach to Carbazoles and Pyridoindoles from Oxindoles via Indole Intermediates

Synthesis and biological evaluation of 6-substituted indolizinoquinolinediones as catalytic DNA topoisomerase I inhibitors

Natural Products, Synthetic and Non-Nucleoside Compounds as Inhibitors of Enzymes Related to DNA: Update 2013

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