Expedient synthesis and anticancer evaluation of dual‐action 9‐anilinoacridine methyl triazene chimeras

Walunj, Dipak; Egarmina, Katarina; Shpilberg, Ofer; Hershkovitz‐Rokah, Oshrat; Grynszpan, Flavio; Gellerman, Gary

doi:10.1111/cbdd.13776

Cited by 3 publications

(1 citation statement)

References 52 publications

(55 reference statements)

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“…It is worth mentioning that compound 13030 belongs to the acridines family which usually demonstrates antitumor activity, particularly as intercalating agents. Due to the planarity present in their tricyclic system, acridines are able to slide in between the DNA nitrogen bases, and block the DNA replication and transcription processes [27][28][29]. Similarly, compound 57774 has a phenoxazine ring system in its structure which was experimentally proven to bind to DNA and exert anticancer effect [30,31].…”

Section: Molecular Dynamic Studies For Compounds Stability and Fittin...mentioning

confidence: 99%

The Discovery of Potent SHP2 Inhibitors with Anti-Proliferative Activity in Breast Cancer Cell Lines

Ghemrawi

Khair

Hasan

et al. 2022

IJMS

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Despite available treatments, breast cancer is the leading cause of cancer-related death. Knowing that the tyrosine phosphatase SHP2 is a regulator in tumorigenesis, developing inhibitors of SHP2 in breast cells is crucial. Our study investigated the effects of new compounds, purchased from NSC, on the phosphatase activity of SHP2 and the modulation of breast cancer cell lines’ proliferation and viability. A combined ligand-based and structure-based virtual screening protocol was validated, then performed, against SHP2 active site. Top ranked compounds were tested via SHP2 enzymatic assay, followed by measuring IC50 values. Subsequently, hits were tested for their anti-breast cancer viability and proliferative activity. Our experiments identified three compounds 13030, 24198, and 57774 as SHP2 inhibitors, with IC50 values in micromolar levels and considerable selectivity over the analogous enzyme SHP1. Long MD simulations of 500 ns showed a very promising binding mode in the SHP2 catalytic pocket. Furthermore, these compounds significantly reduced MCF-7 breast cancer cells’ proliferation and viability. Interestingly, two of our hits can have acridine or phenoxazine cyclic system known to intercalate in ds DNA. Therefore, our novel approach led to the discovery of SHP2 inhibitors, which could act as a starting point in the future for clinically useful anticancer agents.

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Section: Molecular Dynamic Studies For Compounds Stability and Fittin...mentioning

confidence: 99%

The Discovery of Potent SHP2 Inhibitors with Anti-Proliferative Activity in Breast Cancer Cell Lines

Ghemrawi

Khair

Hasan

et al. 2022

IJMS

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A novel, dual action chimera comprising DNA methylating agent and near-IR xanthene-cyanine photosensitizer for combined anticancer therapy

Thankarajan

Walunj

Bazylevich

et al. 2022

Photodiagnosis and Photodynamic Therapy

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Acridine as an Anti-Tumour Agent: A Critical Review

et al. 2022

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This review summarized the current breakthroughs in the chemistry of acridines as anti-cancer agents, including new structural and biologically active acridine attributes. Acridine derivatives are a class of compounds that are being extensively researched as potential anti-cancer drugs. Acridines are well-known for their high cytotoxic activity; however, their clinical application is restricted or even excluded as a result of side effects. The photocytotoxicity of propyl acridine acts against leukaemia cell lines, with C1748 being a promising anti-tumour drug against UDP-UGT’s. CK0403 is reported in breast cancer treatment and is more potent than CK0402 against estrogen receptor-negative HER2. Acridine platinum (Pt) complexes have shown specificity on the evaluated DNA sequences; 9-anilinoacridine core, which intercalates DNA, and a methyl triazene DNA-methylating moiety were also studied. Acridine thiourea gold and acridinone derivatives act against cell lines such as MDA-MB-231, SK-BR-3, and MCF-7. Benzimidazole acridine compounds demonstrated cytotoxic activity against Dual Topo and PARP-1. Quinacrine, thiazacridine, and azacridine are reported as anti-cancer agents, which have been reported in the previous decade and were addressed in this review article.

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Expedient synthesis and anticancer evaluation of dual‐action 9‐anilinoacridine methyl triazene chimeras

Cited by 3 publications

References 52 publications

The Discovery of Potent SHP2 Inhibitors with Anti-Proliferative Activity in Breast Cancer Cell Lines

The Discovery of Potent SHP2 Inhibitors with Anti-Proliferative Activity in Breast Cancer Cell Lines

A novel, dual action chimera comprising DNA methylating agent and near-IR xanthene-cyanine photosensitizer for combined anticancer therapy

Acridine as an Anti-Tumour Agent: A Critical Review

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