Design, synthesis and biological evaluation of novel perimidine o-quinone derivatives as non-intercalative topoisomerase II catalytic inhibitors

Zhou, Du-Chao; Lu, Yuting; Mai, Yan-Wen; Zhang, Chen; Xia, Jie; Yao, Pei-Fen; Wang, Honggen; Huang, Shi‐Liang; Huang, Zhi‐Shu

doi:10.1016/j.bioorg.2019.103131

“…The unwinding effect is caused by certain compounds intercalating into the DNA, and the effect may yield false positive outcomes in the Topo-mediated DNA relaxation assay [40] . In order to determine the intercalating or non-intercalating ability of these compounds, a DNA unwinding assay was carried out using supercoiled pBR322 DNA as substrate and EB as control [3,8] . As shown in Fig.…”

Section: Dna Unwinding Assaymentioning

confidence: 99%

“…Following the clinical success of the DNA-intercalating topo II inhibitors doxorubicin, mitoxantrone, and analogues as anticancer drugs, a great deal of work has been devoted toward other classes of compounds with similar overall topology as topo II inhibitors [5][6][7] . Topoisomerase (Topo) was an enzyme that primarily addresses the conformational problems that arise in DNA during recombination, replication, transcription, and repair [8][9][10] . It was a dependent enzyme for eukaryotic cell proliferation and survival [11] .…”

Section: Introductionmentioning

confidence: 99%

Synthesis and biological evaluation of xanthone derivatives as anti-cancer agents targeting topoisomerase II and DNA

Song

¹

,

Zhu

²

,

Yang

³

et al. 2022

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Topoisomerase is one of the most important targets of anticancer drugs. In order to develop effective and low-toxic topoisomerase inhibitors, a series of xanthone derivatives have been designed and synthesized using the principles of skeleton transition. In vitro growth inhibition experiments of human breast cancer(MCF-7), gastric cancer (MGC-803), and cervical cancer(Hela) cell lines were used to evaluate the compound's anti-tumor cell proliferation activity. Most of the compounds showed anti-tumor growth activity, and also showed low toxicity to human normal cells L929. In the enzyme activity inhibition experiment, compounds 7d and 8d showed the best inhibitory activity. The DNA binding studies disclosed that the most potent compounds 7d and 8d can intercalate into DNA, induce apoptosis in MGC-803 cells and arrested at G2/M phase. Molecular docking showed that compounds 7d and 8d could bind with topoisomerase II and DNA through hydrogen bonds and π-stacking interactions.

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“…Compounds 19c and 20a showed high potency against P. aeruginosa and E. coli (Scheme 14). A library of novel perimidine o-quinone conjugates was developed and examined for cytotoxicity against the four human cancer cell lines HL-60, Huh7, Hct116, and Hela by Zhou et al [138]. All of the compounds showed profound anti-proliferative activity and SARs study explained that the position of o-quinone in ring A or ring B and presence of EWG (electron-withdrawing group) at the C-2 position played an important role in controlling the cytotoxicity of the cell lines.…”

Section: Biologic Applicationsmentioning

confidence: 99%

Recent Advances in the Synthesis of Perimidines and their Applications

Sahiba¹,

Agarwal²

2020

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Perimidines are versatile scaffolds and a fascinating class of N-heterocycles that have evolved significantly in recent years due to their immense applications in life sciences, medical sciences, and industrial chemistry. Their ability of molecular interaction with different proteins, complex formation with metals, and distinct behavior in various ranges of light makes them more appealing and challenging for future scientists. Various novel technologies have been developed for the selective synthesis of perimidines and their conjugated derivatives. These methods extend to the preparation of different bioactive and industrially applicable molecules. This review aims to present the most recent advancements in perimidine synthesis under varied conditions like MW radiation, ultrasound, and grinding using different catalysts such as ionic liquids, acid, metal, and nanocatalyst and also under green environments like catalyst and solvent-free synthesis. The applications of perimidine derivatives in drug discovery, polymer chemistry, photo sensors, dye industries, and catalytic activity in organic synthesis are discussed in this survey. This article is expected to be a systematic, authoritative, and critical review on the chemistry of perimidines that compiles most of the state-of-art innovation in this area.

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“…Following the clinical success of the DNA-intercalating topo II inhibitors doxorubicin, mitoxantrone, and analogues as anticancer drugs, a great deal of work has been devoted toward other classes of compounds with similar overall topology as topo II inhibitors [5][6][7] . Topoisomerase (Topo) was an enzyme that primarily addresses the conformational problems that arise in DNA during recombination, replication, transcription, and repair [8][9][10] . It was a dependent enzyme for eukaryotic cell proliferation and survival [11] .…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Biological Evaluation of Xanthone Derivatives as Anti-Cancer Agents Targeting Topoisomerase II and DNA

Song¹,

Zhu²,

Yang³

et al. 2021

Preprint

0

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Topoisomerase is one of the most important targets of anticancer drugs. In order to develop effective and low-toxic topoisomerase inhibitors, a series of xanthone derivatives have been designed and synthesized using the principles of skeleton transition. In vitro growth inhibition experiments of human breast cancer(MCF-7), gastric cancer (MGC-803), and cervical cancer(Hela) cell lines were used to evaluate the compound's anti-tumor cell proliferation activity. Most of the compounds showed anti-tumor growth activity, and also showed low toxicity to human normal cells L929. In the enzyme activity inhibition experiment, compounds 7d and 8d showed the best inhibitory activity. The DNA binding studies disclosed that the most potent compounds 7d and 8d can intercalate into DNA, induce apoptosis in MGC-803 cells and arrested at G2/M phase. Molecular docking showed that compounds 7d and 8d could bind with topoisomerase II and DNA through hydrogen bonds and π-stacking interactions.

show abstract

Design, synthesis and biological evaluation of novel perimidine o-quinone derivatives as non-intercalative topoisomerase II catalytic inhibitors

Cited by 28 publications

References 17 publications

Synthesis and biological evaluation of xanthone derivatives as anti-cancer agents targeting topoisomerase II and DNA

Synthesis and biological evaluation of xanthone derivatives as anti-cancer agents targeting topoisomerase II and DNA

Recent Advances in the Synthesis of Perimidines and their Applications

Synthesis and Biological Evaluation of Xanthone Derivatives as Anti-Cancer Agents Targeting Topoisomerase II and DNA

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