Discovery of new pyrimido[5,4-c]quinolines as potential antiproliferative agents with multitarget actions: Rapid synthesis, docking, and ADME studies

Mekheimer, Ramadan Ahmed; Allam, Samar M.R.; Al‐Sheikh, Mariam A.; Moustafa, Moustafa Sh.; Al‐Mousawi, Saleh; Mostafa, Yaser A.; Youssif, Bahaa G.M.; Gomaa, Hesham A.M.; Hayallah, Alaa M.; Abdel‐Aziz, Mohamed; Sadek, Kamal Usef

doi:10.1016/j.bioorg.2022.105693

Cited by 32 publications

(40 citation statements)

References 49 publications

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“…Compounds VIc , VIf , VIg , VIi , and VIk were further investigated for their potential to inhibit the CDK2 enzyme 32 . The IC 50 values are shown in Table 2 .…”

Section: Resultsmentioning

confidence: 99%

Novel piperine-carboximidamide hybrids: design, synthesis, and antiproliferative activity via a multi-targeted inhibitory pathway

Al-Wahaibi

Mahmoud

Mostafa

et al. 2022

Journal of Enzyme Inhibition and Medicinal Chemistry

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A new series of piperine-carboximidamide hybrids VIa-k was developed as a new cytotoxic agent targeting EGFR, BRAF, and CDK2. The antiproliferative effect against four cancer cells was investigated against erlotinib. Hybrids VIc , VIf , VIg , VIi , and VIk have the highest antiproliferative activity. Compounds VIc , VIf , VIg , VIi , and VIk inhibited EGFR with IC 50 values ranging from 96 to 127 nM. Compounds VIf and VIk had the most potent inhibitory activity as BRAF V600E (IC 50 = 49 and 40 nM, respectively) and were discovered to be potent inhibitors of cancer cell proliferation (GI 50 = 44 and 35 nM against four cancer cell lines, respectively). Compound VIk , the most effective derivative as an antiproliferative agent, demonstrated potent anti-CDK2 action with an IC 50 value of 12 nM, which is 1.5-fold more potent than the reference dinaciclib. Finally, VIc , VIf , and VIk have a high capacity to inhibit LOX-IMVI cell line survival.

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“…Compounds VIc , VIf , VIg , VIi , and VIk were further investigated for their potential to inhibit the CDK2 enzyme 32 . The IC 50 values are shown in Table 2 .…”

Section: Resultsmentioning

confidence: 99%

Novel piperine-carboximidamide hybrids: design, synthesis, and antiproliferative activity via a multi-targeted inhibitory pathway

Al-Wahaibi

Mahmoud

Mostafa

et al. 2022

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…DNA types I and II Topoisomerases are called for the nucleotides they split if they only divide one or two DNA strands. Topoisomerases are commonly employed as prospective targets in cancer therapy because they play a crucial role in DNA replication, recombination, and transcription (Mekheimer et al, 2022). Camptothecin was the initial recognized topoisomerase I inhibitor, but its chemical instability and cellular resistance restricted its advantage.…”

Section: Biological Actionsmentioning

confidence: 99%

“…Recently, novel hybrid compounds of quinazolin‐4‐one and phenol scaffolds (Mekheimer et al, 2022) were discovered (Pele et al, 2022). Their antioxidant capacity was tested in vitro.…”

Section: Biological Actionsmentioning

confidence: 99%

A comprehensive review of recent advances in the biological activities of quinazolines

Gomaa

2022

Chem Biol Drug Des

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Quinazoline heterocycles are critical in the development of medications.Quinazoline derivatives have been intensively researched, providing a wide range of compounds with diverse biological roles. The quinazoline nucleus has garnered a lot of attention in medical chemistry in recent years. It was assumed to be a pharmacophore component in the development of physiologically interesting drugs. This review is an attempt to increase the potential of quinazoline by highlighting a wide range of advancements demonstrated by numerous derivatives of the quinazoline moiety, as well as focusing on diverse pharmacological actions of the quinazoline moiety. This review compiles recent studies on the quinazoline moiety described in the literature by researchers.

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“…Some mechanisms for the anticancer effects of pyrimido[4,5- b ]quinolines were reported including the inhibition of vascular epithelial growth factor receptor tyrosine kinase, 12 topoisomerases I and Epidermal growth factor receptor. 13 In other case, pyrimido[4,5- b ]quinolines showed the anticancer effects through caspase-3 activation. They also inhibited tubulin polymerization, arrested cell cycle at G2/M phase and induced apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Microwave-assisted multicomponent synthesis of antiproliferative 2,4-dimethoxy-tetrahydropyrimido[4,5-b]quinolin-6(7H)-ones

et al. 2022

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Discovery of new pyrimido[5,4-c]quinolines as potential antiproliferative agents with multitarget actions: Rapid synthesis, docking, and ADME studies

Cited by 32 publications

References 49 publications

Novel piperine-carboximidamide hybrids: design, synthesis, and antiproliferative activity via a multi-targeted inhibitory pathway

Novel piperine-carboximidamide hybrids: design, synthesis, and antiproliferative activity via a multi-targeted inhibitory pathway

A comprehensive review of recent advances in the biological activities of quinazolines

Microwave-assisted multicomponent synthesis of antiproliferative 2,4-dimethoxy-tetrahydropyrimido[4,5-b]quinolin-6(7H)-ones

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