Phthalazinone Scaffold: Emerging Tool in the Development of Target Based Novel Anticancer Agents

Singh, Jyoti; Suryan, Amruta; Kumar, Sandeep; Sharma, Shweta

doi:10.2174/1871520620666200807220146

Cited by 6 publications

(2 citation statements)

References 108 publications

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“…Phthalazin-1(2H)-one core is a privileged building block for drug development, since phthalazinone derivatives possess a wide spectrum of pharmacological activities, including anticancer, antidiabetic, antiasthmatic, antihistaminic, antihypertensive, antithrombotic, antidepressant, anti-inflammatory and analgesic effects [ 7 , 8 , 9 ]. Several 4-substituted phthalazinones, such as olaparib ( 1 ) and compound 2 ( Figure 1 ), are recognized antitumor agents acting through poly ADP ribose polymerase (PARP) inhibition [ 10 , 11 , 12 ]; pyrazole-phthalazinone hybrids, such as compound 3 , are also promising drug candidates for cancer treatment, acting as aurora kinase inhibitors [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

“…The target hybrids could be considered as phthalazinone analogues of brassinin ( 5 ), in which the indole nucleus was exchanged for a phthalazinone moiety with different substitution patterns at C4 and the S-methyl group was replaced by unsaturated fragments of different sizes, such as propargyl, benzyl or several p -substituted benzyl groups, some of them present in brassinin analogues and related compounds with potent antiproliferative activity [ 17 , 18 ]. In addition, since the N2 and C4 positions appear to be important for modulating the anticancer activity of the phthalazinone core [ 7 , 8 , 26 ], we have explored both locations to include the dithiocarbamate scaffold. Herein, we describe the synthesis, in vitro antiproliferative activity, and structure-activity relationships for these novel phthalazinone-dithiocarbamate hybrids 6 – 9 .…”

Section: Introductionmentioning

confidence: 99%

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Novel Phthalazin-1(2H)-One Derivatives Displaying a Dithiocarbamate Moiety as Potential Anticancer Agents

et al. 2022

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Nowadays, cancer disease seems to be the second most common cause of death worldwide. Molecular hybridization is a drug design strategy that has provided promising results against multifactorial diseases, including cancer. In this work, two series of phthalazinone-dithiocarbamate hybrids were described, compounds 6–8, which display the dithiocarbamate scaffold at N2, and the compounds 9, in which this moiety was placed at C4. The proposed compounds were successfully synthesized via the corresponding aminoalkyl phthalazinone derivatives and using a one-pot reaction with carbon disulfide, anhydrous H3PO4, and different benzyl or propargyl bromides. The antiproliferative effects of the titled compounds were explored against three human cancer cell lines (A2780, NCI-H460, and MCF-7). The preliminary results revealed significant differences in activity and selectivity depending on the dithiocarbamate moiety location. Thus, in general terms, compounds 6–8 displayed better activity against the A-2780 and MCF-7 cell lines, while most of the analogues of the 9 group were selective toward the NCI-H460 cell line. Compounds 6e, 8e, 6g, 9a–b, 9d, and 9g with IC50 values less than 10 µM were the most promising. The drug-likeness and toxicity properties of the novel phthalazinone-dithiocarbamate hybrids were predicted using Swiss-ADME and ProTox web servers, respectively.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Novel Phthalazin-1(2H)-One Derivatives Displaying a Dithiocarbamate Moiety as Potential Anticancer Agents

et al. 2022

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Facile Synthesis of Phthalazinone/Isoindolinone Substituted Fluorescence Active Indolo[1,2‐a]quinoxaline Derivatives via ANRORC and Fluorescence Turn Off Sensing of Fe²⁺

Dhurey,

Sarkar,

Pramanik

2024

Helvetica Chimica Acta

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Synthesis of a series of indolo[1,2‐a]quinoxaline derivatives substituted with phthalazinones/isoindolinones/carbonyl benzoylesters at C‐4 position have been accomplished under open air rt/heating conditions following ANRORC (Addition of Nucleophile, Ring Opening and Ring Closure) mechanism. Initially condensation of 2‐(1‐indolyl)‐aniline and ninhydrin generates a spirocyclic intermediate 5'H‐spiro[indene‐2,6'‐indolo[1,2‐a]quinoxaline]‐1,3‐dione, which upon reaction with various nucleophiles like hydrazine/phenylhydrazine, amines and alcohols affords C‐4 substituted indolo[1,2‐a]quinoxalines in high yield (up to ~88%) via ANRORC. The photophysical investigation shows that the quinoxaline derivatives possess significant fluorescence property with high quantum yield (QY~11.0‐17.0). The N‐phenylphthalazinone substituted indolo[1,2‐a]quinoxaline, a molecule structurally similar to 2,2'‐bipyridine system, can efficiently and selectively detect Fe2+ through fluorescence turn off sensing.

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Pyridazinones: A versatile scaffold in the development of potential target‐based novel anticancer agents

Singh

Kumar²,

Silakari

et al. 2022

Journal of Heterocyclic Chem

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Pyridazinones are important nitrogen-rich heterocyclic core that has been driving the substantial medicinal interest due to their wide range of biological activities. This privileged scaffold forms a central core in numerous potent compounds, which results in the development of novel anticancer drugs with fruitful biological activities. The current review article summarizes the progressive development of novel pyridazinone derivatives that are targets for numerous receptors such as C-met kinase inhibitors, PARP inhibitors, Tubulin polymerization inhibitors, Dihydro folate reductase inhibitors, B-Raf inhibitors, Bruton tyrosine kinase inhibitors, FER tyrosine kinase inhibitors, and fibroblast growth factors receptors. It features the various simple techniques for the synthesis of pyridazinones and also highlights the mechanistic insights into the anticancer properties of pyridazinone derivatives.

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Phthalazinone Scaffold: Emerging Tool in the Development of Target Based Novel Anticancer Agents

Cited by 6 publications

References 108 publications

Novel Phthalazin-1(2H)-One Derivatives Displaying a Dithiocarbamate Moiety as Potential Anticancer Agents

Novel Phthalazin-1(2H)-One Derivatives Displaying a Dithiocarbamate Moiety as Potential Anticancer Agents

Facile Synthesis of Phthalazinone/Isoindolinone Substituted Fluorescence Active Indolo[1,2‐a]quinoxaline Derivatives via ANRORC and Fluorescence Turn Off Sensing of Fe²⁺

Pyridazinones: A versatile scaffold in the development of potential target‐based novel anticancer agents

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Phthalazinone Scaffold: Emerging Tool in the Development of Target Based Novel Anticancer Agents

Cited by 6 publications

References 108 publications

Novel Phthalazin-1(2H)-One Derivatives Displaying a Dithiocarbamate Moiety as Potential Anticancer Agents

Novel Phthalazin-1(2H)-One Derivatives Displaying a Dithiocarbamate Moiety as Potential Anticancer Agents

Facile Synthesis of Phthalazinone/Isoindolinone Substituted Fluorescence Active Indolo[1,2‐a]quinoxaline Derivatives via ANRORC and Fluorescence Turn Off Sensing of Fe2+

Pyridazinones: A versatile scaffold in the development of potential target‐based novel anticancer agents

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Facile Synthesis of Phthalazinone/Isoindolinone Substituted Fluorescence Active Indolo[1,2‐a]quinoxaline Derivatives via ANRORC and Fluorescence Turn Off Sensing of Fe²⁺