Antitumor activity, multitarget mechanisms, and molecular docking studies of quinazoline derivatives based on a benzenesulfonamide scaffold: Cell cycle analysis

El‐Azab, Adel S.; Abdel‐Aziz, Alaa A.‐M.; Alsaif, Nawaf A.; Alkahtani, Hamad M.; Alanazi, Mohammed M.; Obaidullah, Ahmad J.; Eskandrani, Razan O.; Alharbi, Amal

doi:10.1016/j.bioorg.2020.104345

Cited by 25 publications

(34 citation statements)

References 15 publications

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“…Chemistry 1 and 2) taken from nine human tissue (i.e. blood, lung, colon, brain, skin, ovary, kidney, prostate, and breast) 17,40,70 . We performed the initial antitumor evaluation at a single dose concentration of 10 mM and calculated the GI in the 59 cell lines.…”

Section: Resultsmentioning

confidence: 99%

“…EGFR and HER2 overexpression has been found in various cancers, such as prostate, breast, colon, and ovarian cancers, and their inhibition results in apoptotic-inducing activity in lung and breast cancers [36][37][38][39] . Therefore, EGFR and HER2 are important targets for antitumor agent design and development 27,32,33,[39][40][41][42] . Several tyrosine kinase inhibitors, such as imatinib (I), gefitinib (II), lapatinib (III), sorafenib (IV), afatinib (V), and sunitinib (VI), are used to treat various cancers (Figure 1) [43][44][45][46][47][48][49][50] .…”

Section: Introductionmentioning

confidence: 99%

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Synthesis, potential antitumor activity, cell cycle analysis, and multitarget mechanisms of novel hydrazones incorporating a 4-methylsulfonylbenzene scaffold: a molecular docking study

Abdel‐Aziz

El‐Azab

Alsaif

et al. 2021

Journal of Enzyme Inhibition and Medicinal Chemistry

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Hydrazone is a bioactive pharmacophore that can be used to design antitumor agents. We synthesised a series of hydrazones (compounds 4-24) incorporating a 4-methylsulfonylbenzene scaffold and analysed their potential antitumor activity. Compounds 6, 9, 16, and 20 had the most antitumor activity with a positive cytotoxic effect (PCE) of 52/59, 27/59, 59/59, and 59/59, respectively, while compounds 5, 10, 14, 15, 18, and 19 had a moderate antitumor activity with a PCE of 11/59-14/59. Compound 20 was the most active and had a mean 50% cell growth inhibition (GI 50 ) of 0.26 mM. Compounds 9 and 20 showed the highest inhibitory activity against COX-2, with a half-maximal inhibitory concentration (IC 50 ) of 2.97 and 6.94 lM, respectively. Compounds 16 and 20 significantly inhibited EGFR (IC 50 ¼ 0.2 and 0.19 lM, respectively) and HER2 (IC 50 ¼ 0.13 and 0.07 lM, respectively). Molecular docking studies of derivatives 9, 16, and 20 into the binding sites of COX-2, EGFR, and HER2 were carried out to explore the interaction mode and the structural requirements for antitumor activity.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Synthesis, potential antitumor activity, cell cycle analysis, and multitarget mechanisms of novel hydrazones incorporating a 4-methylsulfonylbenzene scaffold: a molecular docking study

Abdel‐Aziz

El‐Azab

Alsaif

et al. 2021

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…The most active derivatives, that is, 2, 3, 8, 10, and 11, were subjected to the EGFR TK inhibition assay 7,10,[23][24][25] . The results revealed that several of the tested compounds were promising EGFR TK inhibitors (Table 2).…”

Section: Egfr Tk Inhibition Assaymentioning

confidence: 99%

“…It consists of four distinct phases: the G1 phase, S phase (synthesis), G2 phase, and M phase 23,24,[50][51][52] . Apoptosis, that is, programmed cell death, is considered an important target of the most anti-tumour agents, resulting in G2/M arrest 23,24,[50][51][52] . Our promising derivatives 3 and 11 were subjected to cell cycle analysis and an apoptotic assay to investigate their roles in the cell cycle progression of HCT-116 and MCF-7 cells, respectively.…”

Section: Cell Cycle Arrest Analysis and Detection Of Apoptosismentioning

confidence: 99%

“…colon, ovarian, prostate, and breast cancer cells) [17][18][19][20] . Hence, simultaneous inhibition of EGFR is expected to provide superior efficacy to single receptor targeting, making EGFR a critical target for the design and development of antitumour agents 15,[21][22][23][24][25][26] . In recent years, afatinib (I), and gefitinib (II), have been reported as effective EGFR inhibitors for the treatment of several cancer types (Figure 1) [27][28][29][30][31][32] .…”

Section: Introductionmentioning

confidence: 99%

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Design, synthesis, and analysis of antiproliferative and apoptosis-inducing activities of nitrile derivatives containing a benzofuran scaffold: EGFR inhibition assay and molecular modelling study

Fares

Selim

Goda

et al. 2021

Journal of Enzyme Inhibition and Medicinal Chemistry

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New cyanobenzofurans derivatives 2-12 were synthesised, and their antiproliferative activity was examined compared to doxorubicin and Afatinib (IC 50 ¼ 4.17-8.87 and 5.5-11.2 mM, respectively). Compounds 2 and 8 exhibited broad-spectrum activity against HePG2 (IC 50 ¼ 16.08-23.67 mM), HCT-116 (IC 50 ¼ 8.81-13.85 mM), and MCF-7 (IC 50 ¼ 8.36-17.28 mM) cell lines. Compounds 2, 3, 8, 10, and 11 were tested as EGFR-TK inhibitors to demonstrate their possible anti-tumour mechanism compared to gefitinib (IC 50 5 0.90 mM). Compounds 2, 3, 10, and 11 displayed significant EGFR TK inhibitory activity with IC 50 of 0.81-1.12 mM. Compounds 3 and 11 induced apoptosis at the Pre-G phase and cell cycle arrest at the G2/ M phase. They also increased the level of caspase-3 by 5.7-and 7.3-fold, respectively. The molecular docking analysis of compounds 2, 3, 10, and 11 indicated that they could bind to the active site of EGFR TK.

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Halogen‐based quinazolin‐4(3H)‐one derivatives as MCF‐7 breast cancer inhibitors: Current developments and structure–activity relationship

Upadhyay,

Tandel,

Patel

2024

Archiv der Pharmazie

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Currently, cancer is a serious health challenge with predominance beyond restrictions. Breast cancer remains one of the major contributors to cancer‐related morbidity and mortality in women. Chemotherapy continues to be crucial in the treatment of all variants of cancer. Several antitumor drugs are presently in different phases of clinical trials, whereas many more have been approved for clinical use. However, these drugs have the potential to cause adverse effects, and certain individuals may become resistant to them, which would eventually reduce the drug's efficacy. Therefore, it is essential to discover, develop, and improve newer anticancer drug molecules that could potentially inhibit proliferative pathways. In recent years, quinazolinone derivatives, more specifically halogen‐substituted 4(3H)‐quinazolinone, have drawn attention as a promising new class of chemotherapeutic agents. In addition, these molecules showed significant inhibition in micromolar ranges when tested in vitro against the MCF‐7 cell line. Therefore, this study aims to emphasize the intriguing versatility of halogen atoms, providing an in‐depth summary and highlighting recent developments in the anticancer properties of halogenated 4(3H)‐quinazolinones. It also features a detailed discussion of the structure–activity relationship (SAR) of various functional groups and their interaction with amino acid residues utilizing molecular docking studies. The intent is to foster novel discoveries that can inspire innovative investigations in this domain. Hence, this study simplifies the drug design and development strategies by prolonging the array of pharmacologically active candidates.

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Antitumor activity, multitarget mechanisms, and molecular docking studies of quinazoline derivatives based on a benzenesulfonamide scaffold: Cell cycle analysis

Cited by 25 publications

References 15 publications

Synthesis, potential antitumor activity, cell cycle analysis, and multitarget mechanisms of novel hydrazones incorporating a 4-methylsulfonylbenzene scaffold: a molecular docking study

Synthesis, potential antitumor activity, cell cycle analysis, and multitarget mechanisms of novel hydrazones incorporating a 4-methylsulfonylbenzene scaffold: a molecular docking study

Design, synthesis, and analysis of antiproliferative and apoptosis-inducing activities of nitrile derivatives containing a benzofuran scaffold: EGFR inhibition assay and molecular modelling study

Halogen‐based quinazolin‐4(3H)‐one derivatives as MCF‐7 breast cancer inhibitors: Current developments and structure–activity relationship

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