Synthesis and molecular docking simulations of novel azepines based on quinazolinone moiety as prospective antimicrobial and antitumor hedgehog signaling inhibitors

Noser, Ahmed A.; El-Barbary, A. A.; Salem, Maha M.; El Salam, Hayam A. Abd; shahien, Mohamed

doi:10.1038/s41598-024-53517-y

Cited by 3 publications

(1 citation statement)

References 37 publications

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“…The construction of N-heterocyclic scaffolds [1][2][3][4] is pivotal in pharmaceutical research and drug development due to their diverse pharmacological effects and versatile structures. In this framework, quinazolinone derivatives exhibit various biological effects [5], including antihypertensive [6], antibacterial [7,8], anticancer [9,10], and anti-inflammatory properties [11]. Additionally, these scaffolds are valuable tools in biochemical and biological studies [12,13], helping to elucidate disease mechanisms and identify potential drug targets [14].…”

Section: Introductionmentioning

confidence: 99%

Unveiling the Untapped Potential of Bertagnini’s Salts in Microwave-Assisted Synthesis of Quinazolinones

Bera,

Behera,

De Luca

et al. 2024

Molecules

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Microwave-assisted organic synthesis (MAOS) has emerged as a transformative technique in organic chemistry, significantly enhancing the speed, efficiency, and selectivity of chemical reactions. In our research, we have employed microwave irradiation to expedite the synthesis of quinazolinones, using water as an eco-friendly solvent and thereby adhering to the principles of green chemistry. Notably, the purification of the product was achieved without the need for column chromatography, thus streamlining the process. A key innovation in our approach is using aldehyde bisulfite adducts (Bertagnini’s salts) as solid surrogates of aldehydes. Bertagnini’s salts offer several advantages over free aldehydes, including enhanced stability, easier purification, and improved reactivity. Green metrics and Eco-Scale score calculations confirmed the sustainability of this approach, indicating a reduction in waste generation and enhanced sustainability outcomes. This methodology facilitates the synthesis of a diverse array of compounds, offering substantial contributions to the field, with potential for widespread applications in pharmaceutical research and beyond.

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Section: Introductionmentioning

confidence: 99%

Unveiling the Untapped Potential of Bertagnini’s Salts in Microwave-Assisted Synthesis of Quinazolinones

Bera,

Behera,

De Luca

et al. 2024

Molecules

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A Novel Fluorescent Probe containing dihydropyrimidinone Analogue for Highly Sensitive, Selective Detection of Al(III) Ions with its Molecular Docking, ADME/T and Anticancer Impact

El‐Nahass,

Bakr,

Hamada

et al. 2024

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In this investigation, a novel and promising chemosensor incorporating a dihydropyrimidinone moiety, namely; (E)‐4‐(4‐(dimethylamino)phenyl)‐5‐(3‐(4‐(dimethylamino)phenyl)acryloyl)‐6‐methyl‐3,4 dihydropyrimidin‐2(1H)‐one (DPDAD), has been successfully synthesized and characterized. The DPDAD chemosensor‘s response was evaluated in diverse solvents with varying polarities, shedding light on its solvatochromic behavior. The assessment of colorimetric and optical sensing attributes toward a range of metal ions such as Al(III), Cr(III), Mn II), Fe(III), Co(II), Ni(II), and Cu(II) was undertaken. Notably, DPDAD displayed discernible color alterations upon interaction with all the examined metal ions, with a significant bathochromic shift observed in the absorption spectra in the presence of Al(III), distinguishing it from the other metal ions. Furthermore, through detailed absorption and emission spectral analyses, DPDAD exhibited remarkable selectivity, sensitivity, and an on‐off‐on switchable behavior specifically with Al(III) ions, over the other metal ions. The binding constant was determined as 0.39×105 M−1, accompanied by a limit of detection (LOD) of 1.03×10−5 M. Notably, the DPDAD′s potential extends beyond metal ion sensing; it was computationally assessed for its capability to inhibit the γ‐secretase enzyme. Moreover, DPDAD′s antioxidant attributes were probed, and its inhibitory effect against a range of cancer cell lines was verified in‐vitro.

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Identification of Novel GANT61 Analogs with Activity in Hedgehog Functional Assays and GLI1-Dependent Cancer Cells

Abu Rabe,

Chdid,

Lamson

et al. 2024

Molecules

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Aberrant activation of hedgehog (Hh) signaling has been implicated in various cancers. Current FDA-approved inhibitors target the seven-transmembrane receptor Smoothened, but resistance to these drugs has been observed. It has been proposed that a more promising strategy to target this pathway is at the GLI1 transcription factor level. GANT61 was the first small molecule identified to directly suppress GLI-mediated activity; however, its development as a potential anti-cancer agent has been hindered by its modest activity and aqueous chemical instability. Our study aimed to identify novel GLI1 inhibitors. JChem searches identified fifty-two compounds similar to GANT61 and its active metabolite, GANT61-D. We combined high-throughput cell-based assays and molecular docking to evaluate these analogs. Five of the fifty-two GANT61 analogs inhibited activity in Hh-responsive C3H10T1/2 and Gli-reporter NIH3T3 cellular assays without cytotoxicity. Two of the GANT61 analogs, BAS 07019774 and Z27610715, reduced Gli1 mRNA expression in C3H10T1/2 cells. Treatment with BAS 07019774 significantly reduced cell viability in Hh-dependent glioblastoma and lung cancer cell lines. Molecular docking indicated that BAS 07019774 is predicted to bind to the ZF4 region of GLI1, potentially interfering with its ability to bind DNA. Our findings show promise in developing more effective and potent GLI inhibitors.

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Synthesis and molecular docking simulations of novel azepines based on quinazolinone moiety as prospective antimicrobial and antitumor hedgehog signaling inhibitors

Cited by 3 publications

References 37 publications

Unveiling the Untapped Potential of Bertagnini’s Salts in Microwave-Assisted Synthesis of Quinazolinones

Unveiling the Untapped Potential of Bertagnini’s Salts in Microwave-Assisted Synthesis of Quinazolinones

A Novel Fluorescent Probe containing dihydropyrimidinone Analogue for Highly Sensitive, Selective Detection of Al(III) Ions with its Molecular Docking, ADME/T and Anticancer Impact

Identification of Novel GANT61 Analogs with Activity in Hedgehog Functional Assays and GLI1-Dependent Cancer Cells

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