Synthesis of novel pyrimido[4,5‐<i>b</i>]quinolines as potential anticancer agents and HER2 inhibitors

Ibrahim, Nahla Said M.; Kadry, Hanan H.; Zaher, Ashraf F.; Mohamed, Khaled O.

doi:10.1111/cbdd.14307

Cited by 4 publications

(3 citation statements)

References 80 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Ibrahim et al [47] . discussed the active moieties of the molecule N ‐(2‐methyl‐4‐(pyrimido[4,5‐b]quinolin‐4‐ylamino)phenyl)benzamide (Figure 1).…”

Section: Building Blocks Of Bioactivitymentioning

confidence: 99%

See 1 more Smart Citation

Recent Advancements and Developments in the Biological Importance of Pyrimido[4,5‐b]Quinoline Scaffolds

Hammouda,

Rashed,

Abo El‐Yazeed

et al. 2024

ChemistrySelect

View full text Add to dashboard Cite

This study highlights the biological efficiency of pyrimido[4,5‐b]quinolines as inhibitors of cancer cell growth and antioxidants and anti‐inflammatory properties, etc. Recent research studies have revealed their promising biological activity to inhibit the growth of many disease‐causing yeasts, fungi, and bacteria. The structural composition greatly affects the biological effectiveness, as these compounds exceed the value of some standard compounds against pathogenic microbes. The antioxidant potential of these derivatives is also explored. Several glycosylated and non‐glycosylated derivatives exhibited potent free radical scavenging activity and protected against DNA damage, exceeding reference standards in some cases. Furthermore, the review examines the anti‐inflammatory and analgesic properties of pyrimidoquinoline derivatives. Studies suggest their efficacy is comparable to known drugs like diclofenac and aspirin in carrageenan‐induced paw edema and hot plate tests. Pyrimidoquinoline derivatives also demonstrate promising anticancer activity. While some have minimal effects, others exhibit notable activity against various human cancer cell lines. This review documents over two decades of research, covering the period from 2000 to 2024. Overall, pyrimidoquinoline derivatives signify an auspicious class of compounds with therapeutic potential across various areas. Further research is necessary to elucidate their mechanisms of action, optimize their efficacy and selectivity, and assess their safety profiles for clinical development.

show abstract

“…Ibrahim et al [47] . discussed the active moieties of the molecule N ‐(2‐methyl‐4‐(pyrimido[4,5‐b]quinolin‐4‐ylamino)phenyl)benzamide (Figure 1).…”

Section: Building Blocks Of Bioactivitymentioning

confidence: 99%

“…Ibrahim et al [47] . synthesized N ‐arylpyrimidoquinolines ( 168 a – e ) and 2‐aryl‐2,3‐dihydropyrimidoquinoline‐4(1 H )‐ones ( 169 a – e ) to explore their potential for treating breast cancer (Table 37).…”

Section: Biological Propertiesmentioning

confidence: 99%

Recent Advancements and Developments in the Biological Importance of Pyrimido[4,5‐b]Quinoline Scaffolds

Hammouda,

Rashed,

Abo El‐Yazeed

et al. 2024

ChemistrySelect

View full text Add to dashboard Cite

show abstract

“…[35][36][37] Accordingly, the combination of these two classes in pyrimidoquinoline derivatives has become a subject of interest. [38] In recent years, different structures have been developed to inhibit the EGFR family, such as gefitinib, erlotinib, EGFR/HER2 dual-acting lapatinib, and TAK-285 (Figure 1), with similar structure features of a hydrophobic head, NH linker, central nitrogen-containing heterocyclic ring, and hydrophobic tail. [39][40][41][42] Motivated by the above-mentioned findings, the present study involves the synthesis and pharmacological evaluation of substituted pyrimidoquinolines as anticancer agents.…”

mentioning

confidence: 99%

Synthesis of novel pyrimido[4,5‐b]quinoline derivatives as dual EGFR/HER2 inhibitors as anticancer agents

Ibrahim,

Kadry,

Zaher

et al. 2023

Archiv der Pharmazie

Self Cite

View full text Add to dashboard Cite

A series of novel N‐aryl‐5‐aryl‐6,7,8,9‐tetrahydropyrimido[4,5‐b]quinolin‐4‐amines 4a–4l was synthesized as potential anticancer agents through Dimroth rearrangement reaction of intermediates 3a–3c. Pyrimido[4,5‐b]quinolines 4a–4l showed promising activity against the Michigan Cancer Foundation‐7 (MCF‐7) cell line, compared with lapatinib as the reference drug. Compounds 4d, 4h, 4i, and 4l demonstrated higher cytotoxic activity than lapatinib, with IC50 values of 2.67, 6.82, 4.31, and 1.62 µM, respectively. Compounds 4d, 4i, and 4l showed promising epidermal growth factor receptor (EGFR) inhibition with IC50 values of 0.065, 0.116, and 0.052 µM, respectively. These compounds were subjected to human epidermal growth factor receptor 2 (HER2) inhibition and showed IC50 values of 0.09, 0.164, and 0.055 µM, respectively. Compounds 4d, 4i, and 4l are good candidates as dual EGFR/HER2 inhibitors. The most active compound, 4l, was subjected to cell‐cycle analysis and induced cell‐cycle arrest at the S phase. Compound 4l induced apoptosis 60‐fold compared with control untreated MCF‐7 cells. 4l can inhibit cancer metastasis. It reduced MCF‐7 cell infiltration and metastasis by 45% compared with control untreated cells.

show abstract

Review: synthesis and anticancer activity of pyrimido[4,5-b]quinolines in the last twenty years

Ibrahim,

Kadry,

Zaher

et al. 2024

Chem. Pap.

View full text Add to dashboard Cite

Pyrimido[4,5-b]quinoline is a vital structural motif. The synthesis of pyrimido[4,5-b]quinolines has been a challenging topic in medicinal chemistry. A wide range of starting materials have been employed to achieve this nucleus such as quinoline derivatives and isatins. Multi-component one-pot synthestic approaches were employed either by using barbituric or thiobarbituric acid, amines and aldehydes or from 6-aminouracils, aldehydes and cyclohexanone derivatives. Recent synthetic strategies and many green chemistry techniques have improved pyrimido[4,5-b]quinolines synthesis over the last twenty years. Among the many reported biological activities of pyrimido[4,5-b]quinolines, anticancer activity attracted research attention over the past couple of decades. Many derivatives have shown promising anticancer activity on different cancer cell lines such as MCF-7, A549, K562 and others. They also demonstrated activity on different enzymes and receptors such as tyrosine kinases, tyrosyl-DNA Phosphodiesterase II and HDM2 ubiquitin ligase (E3) that promote apoptosis, repair DNA damage, and induce cell cycle arrest. This review critically examines the recent synthetic approaches employed for the synthesis of pyrimido[4,5-b]quinolines and explores their reported anticancer activities.

show abstract

Synthesis of novel pyrimido[4,5‐b]quinolines as potential anticancer agents and HER2 inhibitors

Cited by 4 publications

References 80 publications

Recent Advancements and Developments in the Biological Importance of Pyrimido[4,5‐b]Quinoline Scaffolds

Recent Advancements and Developments in the Biological Importance of Pyrimido[4,5‐b]Quinoline Scaffolds

Synthesis of novel pyrimido[4,5‐b]quinoline derivatives as dual EGFR/HER2 inhibitors as anticancer agents

Review: synthesis and anticancer activity of pyrimido[4,5-b]quinolines in the last twenty years

Contact Info

Product

Resources

About