Design, docking, and synthesis of novel indeno[1,2-c]isoquinolines for the development of antitumor agents as topoisomerase I inhibitors

Cho, Won Jea; Le, Quynh Manh; Van, Hue Thi My; Lee, Kwang Youl; Kang, Bok Yun; Lee, Eung Seok; Lee, Sang Kook; Kwon, Young Joo

doi:10.1016/j.bmcl.2007.04.064

Cited by 47 publications

(11 citation statements)

References 12 publications

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“…Not only the indenoisoquinoline-diones, but also the Cocatalysis can be applied to synthesize the potential antitumor medicines. As shown in the Scheme 28, two reported antitumor structures, with extensive utility to against several cell lines, [40] could be also prepared in shorter synthetic pathways and with higher yields.…”

Section: Co-catalyzed Intramolecular 12-insertion Of Iminementioning

confidence: 99%

Transition‐Metal‐Catalyzed Addition/Cyclization Reactions of the C−N Multiple Bonds Containing Species

Hsieh

2021

The Chemical Record

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This article describes our research work for the past decade, which involves the transition-metal-catalyzed cyclization reactions of the CÀ N multiple bonds containing species and their synthetic applications to access various heterocyclic compounds. The concepts of reactions including four types of coupling with a subsequent cyclization are (1) the transitionmetal performs as a Lewis acid to activate a nitrile and accelerate the nucleophilic addition, (2) the transition-metal-catalyzed 1,2-insertion reaction of nitrile, (3) the Cu-catalyzed CÀ N coupling reaction of imine, and (4) the Co-catalyzed addition/cyclization reaction of imine. These methods can be used to synthesize various N-containing aromatic heterocycles with higher efficiency, and can be applied to the synthesis of relevent natural alkaloids, their derivatives as well as biologically active compounds.

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Section: Co-catalyzed Intramolecular 12-insertion Of Iminementioning

confidence: 99%

Transition‐Metal‐Catalyzed Addition/Cyclization Reactions of the C−N Multiple Bonds Containing Species

Hsieh

2021

The Chemical Record

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Section: Topoisomerase Poisonsmentioning

confidence: 99%

“…The Cho group also investigated 5‐substituted indenoisoquinolines (imines, rather than lactams), designed to reduce the conformational entropy of the 3‐arylisoquinolinamines . The ethylenediamine derivative 57 was as potent as 1 against Top1, but considerably less cytotoxic, while the piperazine 58 had improved cytotoxic activity. Interestingly, the ketone appears necessary for activity—reduction to the hydroxyl group, acetylation of the hydroxyl, and deoxygenation all abolish anti‐Top1 activity, suggesting an indenoisoquinoline‐like binding mode, where the ketone acts as a H‐bond acceptor for Arg364 .…”

Section: Topoisomerase Poisonsmentioning

confidence: 99%

Topoisomerase 1B poisons: Over a half‐century of drug leads, clinical candidates, and serendipitous discoveries

Cinelli

2018

Medicinal Research Reviews

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Topoisomerases are DNA processing enzymes that relieve supercoiling (torsional strain) in DNA, are necessary for normal cellular division, and act by nicking (and then religating) DNA strands. Type 1B topoisomerase (Top1) is overexpressed in certain tumors, and the enzyme has been extensively investigated as a target for cancer chemotherapy. Various chemical agents can act as “poisons” of the enzyme’s religation step, leading to Top1‐DNA lesions, DNA breakage, and eventual cellular death. In this review, agents that poison Top1 (and have thus been investigated for their anticancer properties) are surveyed, including natural products (such as camptothecins and indolocarbazoles), semisynthetic camptothecin and luotonin derivatives, and synthetic compounds (such as benzonaphthyridines, aromathecins, and indenoisoquinolines), as well as targeted therapies and conjugates. Top1 has also been investigated as a therapeutic target in certain viral and parasitic infections, as well as autoimmune, inflammatory, and neurological disorders, and a summary of literature describing alternative indications is also provided. This review should provide both a reference for the medicinal chemist and potentially offer clues to aid in the development of new Top1 poisons.

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“…In 1978, Cushman et al reported the indenoisoquinoline as a side product during the synthesis of nitidine chloride . This serendipitous discovery led to identifying a new class of compounds (see Figure ) which was found to be a good alternative of the well-known camptothecin (CPT) class of compounds, known for its DNA topoisomerase I (Top I) inhibitory activity . Later, they developed another route of indenoisoquinoline synthesis and isolated the desired compound in good yield and studied their DNA topoisomerase I (Top I) inhibitory activity. , …”

Section: Introductionmentioning

confidence: 99%

CuO@NiO Nanocomposite Catalyzed Synthesis of Biologically Active Indenoisoquinoline Derivatives

Rawat

2020

ACS Sustainable Chem. Eng.

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Indenoisoquinolines, a noncamptothecin class of synthetic compounds, show a wide range of biological activities, and some of the compounds have shown potent anticancer activity and entered into clinical trials. This stimulated the interest of medicinal chemists to develop new synthetic methodologies for the synthesis of this promising pharmacophore. In order to develop an environmentally benign synthetic method for the synthesis of indenoisoquinolines, a novel CuO@NiO nanocatalyst was prepared by simple calcination of a mixture of malachite as a sustainable copper source and nickel oxalate. The prepared nanocomposite was characterized by PXRD, FESEM, TEM, EDAX, XPS, and BET techniques. The obtained CuO@NiO nanocatalyst was used for the synthesis of indenoisoquinolines using 2-iodobenzamide and 1,3-indanedione as a starting material and ethylene glycol as a green solvent. In comparison to the reported methods, the present methodology has several advantages, such as a wide substrate scope, excellent yield, shorter reaction time, no usage of additive/base, and better values of green chemistry metrices like a low E factor (0.76), high reaction mass efficiency (56.75%), low process mass efficiency (1.76), and a high turnover number (36.69), and the catalyst was recycled up to six times without a major loss in its catalytical activity. Further, a very low-level leaching of copper ions (5.85 ppm) and nickel ions (4.83 ppm) was observed, which is much less than the tolerance limit as per WHO guidelines.

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Design, docking, and synthesis of novel indeno[1,2-c]isoquinolines for the development of antitumor agents as topoisomerase I inhibitors

Cited by 47 publications

References 12 publications

Transition‐Metal‐Catalyzed Addition/Cyclization Reactions of the C−N Multiple Bonds Containing Species

Transition‐Metal‐Catalyzed Addition/Cyclization Reactions of the C−N Multiple Bonds Containing Species

Topoisomerase 1B poisons: Over a half‐century of drug leads, clinical candidates, and serendipitous discoveries

CuO@NiO Nanocomposite Catalyzed Synthesis of Biologically Active Indenoisoquinoline Derivatives

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