One-Pot Synthesis of Benzo[4,5]imidazo[2,1-<i>a</i>]isoquinolines and Isoquinolino[3,4-<i>b</i>]quinoxalines via Tandem Cyclization Strategies

Bagdasarian, Alex L.; Nguyen, Huy H.; Palazzo, Teresa A.; Fettinger, James C.; Haddadin, Makhluf J.; Kurth, Mark J.

doi:10.1021/acs.joc.6b00338

Cited by 14 publications

(6 citation statements)

References 38 publications

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“…The following mechanism was proposed based on similar cyanation reactions done by Haddadin et al 17 DIQ3 and Related Derivatives Reduce the Viability of Human Colon Cancer HCT116 Cell Line in 2D in Vitro Models at Doses That Are Not Cytotoxic to Normal FHs74Int Cells. To assess the antitumor effect of compound DIQ3 and its related derivatives (DIQ4-6) on human colon cancer HCT116 cell lines, we employed the MTT assay.…”

Section: ■ Results and Discussionmentioning

confidence: 93%

Novel 2-(5-Imino-5H-isoquinolones[3,4-b]quinoxalin-7-ylmethyl)-benzonitrile (DIQ3) and Other Related Derivatives Targeting Colon Cancer Cells: Syntheses and in Vitro Models

Monzer¹,

Jabotian²,

Ballout³

et al. 2019

ACS Omega

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Chemotherapy has been shown to be effective in reducing the progression and development of cancer in metastatic patients. However, drug selectivity is still a major issue for most chemotherapeutics. In this study, we synthesized four novel heterocyclic compounds having similarity in structure with quinone systems whereby nitrogen atoms replace the oxygen atoms. The anticancer activity of these compounds ( DIQ3-6 ) was tested against HCT116 human colon cancer cells. We showed that all four heterocycles caused significant reduction in colon cancer cell viability at doses as low as 4 μM, a concentration that was not cytotoxic to normal human FHs74Int intestinal cell lines. Interestingly, these heterocycles inhibited colon sphere formation in 3D cultures at first generation (G 1 ), mainly because of inhibition of proliferation as evidenced by Ki67 staining. Thus, DIQ3 causes sufficient eradication of the self-renewal ability of the highly resistant cancer stem cells. This study represents the first documentation of the activity of these novel heterocyclic compounds, particularly compound DIQ3 , and their potential therapeutic use in targeting colon cancer self-renewal capacity. Our findings provide the basis for proposing these nontoxic and stable compounds for additional testing against cancer.

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Section: ■ Results and Discussionmentioning

confidence: 93%

Novel 2-(5-Imino-5H-isoquinolones[3,4-b]quinoxalin-7-ylmethyl)-benzonitrile (DIQ3) and Other Related Derivatives Targeting Colon Cancer Cells: Syntheses and in Vitro Models

Monzer¹,

Jabotian²,

Ballout³

et al. 2019

ACS Omega

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“…Cyano was selected as a presetting active electrophile for the following reasons. First, cyano is widely used to synthesize various important N‐containing compounds . Second, as an electron‐withdrawing group, cyano can enhance the electrophilicity of adjacent aldehyde carbon.…”

Section: Resultsmentioning

confidence: 99%

Controlled One‐Pot Synthesis of Multiple Heterocyclic Scaffolds Based on an Amphiphilic Claisen‐Schmidt Reaction Intermediate

Song

Huang

et al. 2019

ChemistrySelect

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An efficient one‐pot synthesis method for multiple heterocyclic scaffolds was carried out based on the cyano‐containing amphiphilic Claisen‐Schmidt reaction intermediate. Several valuable heterocyclic compounds including isoindolinone, flavonoid and isobenzofuranone were conveniently synthesized from o‐cyanobenzaldehyde and o‐hydroxyacetophenone by controlling the reaction temperature, catalyst and solvent. In addition, a density functional theory (DFT) based calculation was carried out on the key amphiphilic intermediate for understanding the reaction selectivity in water and non‐aqueous solution.

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“…Benzo[4,5]imidazo[2,1‐a]isoquinolines 155 and isoquinolino[3,4‐b]quinoxalines 156 were obtained via tandem cyclization strategies in reactions with o‐phenylenediamines 154 (Scheme 64). [57] …”

Section: Miscellaneousmentioning

confidence: 99%

Multifaceted Behavior of 2‐Cyanobenzaldehyde and 2‐Acylbenzonitriles in the Synthesis of Isoindolinones, Phthalides and Related Heterocycles

2023

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2‐Cyanobenzaldehye (also called 2‐formylbenzonitrile) and related 2‐acylbenzonitriles belong to a class of bifunctional aromatic compounds that emerged as useful starting materials in developing efficient cascade‐type reactions leading to different heterocyclic compounds. The variety of sometimes unpredictable mechanisms that rise from these structurally simple starting materials renders this class of compounds unique to afford, through divergent cascade reactions, heterocycles like isoindolinones, phthalides (also known with the name of isobenzofuranones), imidates, and in less extent isoindolin‐1‐imine, six‐ and seven‐membered heterocycles, porphyrins, also in asymmetric way exploiting different organocatalytic activation modes. To give a picture, this chemistry can be associated to Goldberg variations which stem from a common motive in a pressing and surprising way. In this Review, emphasis is also given to the synthetic methods for the access to substituted 2‐cyanobenzaldehydes and 2‐acylbenzonitriles which allowed to enlarge the scope of the described cascade reactions.

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One-Pot Synthesis of Benzo[4,5]imidazo[2,1-a]isoquinolines and Isoquinolino[3,4-b]quinoxalines via Tandem Cyclization Strategies

Cited by 14 publications

References 38 publications

Novel 2-(5-Imino-5H-isoquinolones[3,4-b]quinoxalin-7-ylmethyl)-benzonitrile (DIQ3) and Other Related Derivatives Targeting Colon Cancer Cells: Syntheses and in Vitro Models

Novel 2-(5-Imino-5H-isoquinolones[3,4-b]quinoxalin-7-ylmethyl)-benzonitrile (DIQ3) and Other Related Derivatives Targeting Colon Cancer Cells: Syntheses and in Vitro Models

Controlled One‐Pot Synthesis of Multiple Heterocyclic Scaffolds Based on an Amphiphilic Claisen‐Schmidt Reaction Intermediate

Multifaceted Behavior of 2‐Cyanobenzaldehyde and 2‐Acylbenzonitriles in the Synthesis of Isoindolinones, Phthalides and Related Heterocycles

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