Design, synthesis, antiproliferative activity and docking studies of quinazoline derivatives bearing oxazole or imidazole as potential EGFR inhibitors

Ouyang, Yanling; Wang, Caolin; Zhao, Bingbing; Xiong, Hehua; Xiao, Zhen; Zhang, Bingliang; Zheng, Pengwu; Hu, Jiayi; Gao, Yan-Li; Zhang, Manli; Zhu, Wufu; Xu, Shan

doi:10.1039/c8nj03594f

Cited by 13 publications

(7 citation statements)

References 14 publications

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“…The recent decade has seen a number of efforts to quantify the anticancer activities of a series of selected heterocycles on cultivated cancer cell cultures [ 1 , 6 , 7 ]. The results of these efforts outline significant structure-activity trends in a series of quinazoline derivatives [ 6 ], indeno-isoquinoline derivatives, specifically on an isolated MYC-cancer promoter [ 7 ], and more generally in G-quadruplexes of various functions, structures, and sizes, as well as quadruplex targeting heterocyclic ligands [ 8 , 9 , 10 ]. Conversely, the belief that G4-ligands lack selectivity due to targeting multiple quadruplexes and, thus, many different sites in the genome still has an important place in the literature [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Small Heterocyclic Ligands as Anticancer Agents: QSAR with a Model G-Quadruplex

Kaneti

Kurteva²,

Georgieva³

et al. 2022

Molecules

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G-quadruplexes (GQs) have become valid targets for anticancer studies in recent decades due to their multifaceted biological function. Herewith, we aim to quantify interactions of potential heterocyclic ligands (Ls) with model GQs. For seven 4-aminoquinazolines and three 2-heteroaryl perimidines, seven of this ten-membered group so far unknown, we use routine quantum chemical modeling. As shown in the literature, a preferred mode of interaction of heterocycles with cellular structures is stacking to exposable faces of G-quadruplexes. To exploit the energy of this interaction as a molecular descriptor and achieve the necessary chemical precision, we use state of the art large-scale density functional theory (DFT) calculations of stacked heterocycles to a GQ. Actually, the GQ has been simplified for the computation by stripping it off all pentose phosphate residues into a naked model of stacked guanine quartets. The described model thus becomes computable. The obtained heterocyclic ligand GQ.L stacking energies, that is, their GQ affinities, are the necessary ligand descriptors. Using the ligand biological inhibitory activities (IC50) on a human malignant melanoma A375 cell line, we obtain a good linear relationship between computed ligand stacking affinities to GQ, and experimental log (IC50) values. Based on the latter relationship, we discuss a putative mechanism of anticancer activity of heterocyclic ligands via stacking interactions with GQs and thereby controlling cell regulatory activity. This mechanism may tentatively be applied to other condensed five- and six-membered small heterocycles as well.

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Section: Introductionmentioning

confidence: 99%

Small Heterocyclic Ligands as Anticancer Agents: QSAR with a Model G-Quadruplex

Kaneti

Kurteva²,

Georgieva³

et al. 2022

Molecules

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“…In addition, quinazolin-4-ones are also the important intermediates for the synthesis of other nitrogen heterocyclic compounds having physiological and biological activity. 3…”

Section: Introductionmentioning

confidence: 99%

“…For example, the natural alkaloids of luotonin A and luotonin F and the marketing drugs of piriqualone and methapualone are the derivatives of quinazolin-4-one (Scheme ). In addition, quinazolin-4-ones are also the important intermediates for the synthesis of other nitrogen heterocyclic compounds having physiological and biological activity …”

Section: Introductionmentioning

confidence: 99%

Quinazolinone Synthesis through Base-Promoted S_NAr Reaction of ortho-Fluorobenzamides with Amides Followed by Cyclization

Iqbal

Mehmood

et al. 2019

ACS Omega

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A transition-metal-free synthesis of quinazolin-4-ones by Cs 2 CO 3 -promoted S N Ar reaction of ortho -fluorobenzamides with amides followed by cyclization in dimethyl sulfoxide has been developed. The present procedure can provide efficient synthetic methods for the formation of both 2-substituted and 2,3-disubstituted quinazolin-4-one rings depending on the use of easily available starting materials and an efficient, one-pot protocol for the synthesis of the marketed drug product of methaqualone.

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“…In heterocyclic chemistry, the nitrogen atom is considered to be the backbone in most of the molecules that have application in pharmacological and biological discipline such as anti‐tumor, anti‐inflammatory, anti‐hypertensive, anti‐HIV, anti‐bacterial, anti‐convulsant, and anti‐proliferative activity . In this category, the quinazoline derivatives are one of the best anti‐cancer agents and especially selective inhibitors for tyrosine kinase activity of the epidermal growth factor receptor (EGFR) . These inhibitors are used for the treatment of solid tumors such as non‐small lung, breast, prostrate, pancreas and colon cancers.…”

Section: Introductionmentioning

confidence: 99%

2,4‐Diphenyl‐1,2‐dihydroquinazoline Derivatives: Synthesis, Anticancer Activity and Docking Studies

et al. 2019

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A straightforward, rapid and efficient one‐pot method was developed for the synthesis of 2,4 ‐diphenyl‐1,2 dihydroquinazoline and their analogues. The reactions were performed with different type of benzylamine and 2‐bromo benzophenone using ammonium acetate and characterized by 1H NMR, 13C NMR and Mass spectroscopic techniques. All the compounds were tested for MDA‐MB‐231, A549 and DU‐145 type of human cancer cell lines. Among the synthesized compounds, 4 j (4‐phenyl‐2‐(3,4,5‐trimethoxyphenyl)‐1,2‐dihydroquinazoline) and 4 e (2‐(3,4‐dichlorophenyl)‐4‐phenyl‐1,2‐dihydroquinazoline) molecules were found to possess good anticancer activity. The binding nature of these molecules was explored through docking studies.

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Design, synthesis, antiproliferative activity and docking studies of quinazoline derivatives bearing oxazole or imidazole as potential EGFR inhibitors

Abstract: Six series of quinazoline derivatives bearing oxazole or imidazole (8a–f, 9a–f, 10a–d, 11a–f, 12a–d and 13a–i) were designed, synthesized and their IC50 values evaluated against three cancer cell lines (A549, MCF-7 and PC-3).

Cited by 13 publications

References 14 publications

Small Heterocyclic Ligands as Anticancer Agents: QSAR with a Model G-Quadruplex

Small Heterocyclic Ligands as Anticancer Agents: QSAR with a Model G-Quadruplex

Quinazolinone Synthesis through Base-Promoted S_NAr Reaction of ortho-Fluorobenzamides with Amides Followed by Cyclization

2,4‐Diphenyl‐1,2‐dihydroquinazoline Derivatives: Synthesis, Anticancer Activity and Docking Studies

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Design, synthesis, antiproliferative activity and docking studies of quinazoline derivatives bearing oxazole or imidazole as potential EGFR inhibitors

Abstract: Six series of quinazoline derivatives bearing oxazole or imidazole (8a–f, 9a–f, 10a–d, 11a–f, 12a–d and 13a–i) were designed, synthesized and their IC50 values evaluated against three cancer cell lines (A549, MCF-7 and PC-3).

Cited by 13 publications

References 14 publications

Small Heterocyclic Ligands as Anticancer Agents: QSAR with a Model G-Quadruplex

Small Heterocyclic Ligands as Anticancer Agents: QSAR with a Model G-Quadruplex

Quinazolinone Synthesis through Base-Promoted SNAr Reaction of ortho-Fluorobenzamides with Amides Followed by Cyclization

2,4‐Diphenyl‐1,2‐dihydroquinazoline Derivatives: Synthesis, Anticancer Activity and Docking Studies

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Quinazolinone Synthesis through Base-Promoted S_NAr Reaction of ortho-Fluorobenzamides with Amides Followed by Cyclization