Isatin-Schiff's base and chalcone hybrids as chemically apoptotic inducers and EGFR inhibitors; design, synthesis, anti-proliferative activities and in silico evaluation

Fayed, Eman A.; Eldin, Rogy R. Ezz; Mehany, Ahmed B. M.; Bayoumi, Ashraf H.; Ammar, Yousry A.

doi:10.1016/j.molstruc.2021.130159

“…Based on the above findings, and in continuation to our work on the synthesis of new compounds with biological activities [28][29][30][31][32][33][34], we have synthesized a new series of quinolone-3-carboxamide derivatives containing a series of biologically active moites that are expected to be strongly inhibitory for several human cell lines and PIM-1 inhibitors as a result of our commitment to search for new potential anticancer agents related to heterocyclic [35][36][37][38][39][40][41][42]. | P a g e…”

Section: Figure 1: Structures For Pim-1 Inhibitors and The Newly Designed Quinoline Hybridsmentioning

confidence: 58%

“…Doxorubicin were subjected to screening by the Swiss ADMET website (http://www.sib.swiss) interface, provoking the in-silico ADME characteristics and examining their aptitude to exhibit drug-likeliness [54][55][56][57].…”

Section: In-silico Studymentioning

confidence: 99%

Carboxamide appended quinoline moieties as potential anti-proliferative agents, apoptotic inducers and Pim-1 kinase inhibitors

Ammar

¹

,

Elhagali

²

,

Abusaif

³

et al. 2021

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The targeted approach of protein kinases (PKs), as PKs are the main regulators of cell survival and proliferation, has been a promising strategy for treatments for cancer. Here we analyze the potential of quinoline-carboximide derivatives for four cell lines: MCF-7, CACO, HepG-2 and HCT-116 as anticancer agents. 3e, 4b, 11b and 13d derivatives showed good anti-proliferative activities in comparison to the reference standard Doxorubicin, against the four cell lines tested. They have been chosen for further studies. First of all, the IC50 value surveys were carried out to ensure the protection of our hits and demonstrate that the cytotoxic effect (IC50 > 113 μM) is highly selective on normal human cells (WI-38). Secondly, apoptosis was accomplished by down-regulation of Bcl-2 and up-regulation of BAX and Caspase-3 by these active compounds. Also, the Pim-1 inhibitory activity of the active hybrids was done, which indicate that compound 3e was the most active with percentage of inhibition 82.27% and IC50 equal 0.11 when compaired to SGI-1776 as a reference standered. In addition, the in silico assessment of ADME properties, all of the strongest compounds are orally bioavailable without blood brain barrier penetration.

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“…Doxorubicin were subjected to screening by the Swiss ADMET website (http://www.sib.swiss) interface, provoking the in-silico ADME characteristics and examining their aptitude to exhibit drug-likeliness [54][55][56][57].…”

Section: In-silico Studymentioning

confidence: 99%

“…It has now been documented to be effective for cancer therapy [27] and for reduction of undesirable side effects [17] by developing a single molecule with more than one pharmacopher with different action modes. with biological activities [28][29][30][31][32][33][34], we have synthesized a new series of quinolone-3-carboxamide derivatives containing a series of biologically active moites that are expected to be strongly inhibitory for several human cell lines and PIM-1 inhibitors as a result of our commitment to search for new potential anticancer agents related to heterocyclic [35][36][37][38][39][40][41][42]. N-(4-Aminophenyl)-2-cyanoacetamide (8) [44] has two nucleophilic centers which may be to react with the aldehyde function of 1.…”

Section: Introducionmentioning

confidence: 99%

Carboxamide Appended Quinoline Moieties as Potential Antiproliferative Agents, Apoptotic Inducers and Pim-1 Kinase Inhibitors

Ammar

¹

,

Elhagali

²

,

Abusaif

³

et al. 2021

Preprint

Self Cite

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The targeted approach of protein kinases (PKs), as PKs are the main regulators of cell survival and proliferation, has been a promising strategy for treatments for cancer. Here we analyze the potential of quinoline-carboximide derivatives for four cell lines: MCF-7, CACO, HepG-2 and HCT-116 as anticancer agents. 3e, 4b, 11b and 13d derivatives showed good anti-proliferative activities in comparison to the reference standard Doxorubicin, against the four cell lines tested. They have been chosen for further studies. First of all, the IC50 value surveys were carried out to ensure the protection of our hits and demonstrate that the cytotoxic effect (IC50 > 113 μM) is highly selective on normal human cells (WI-38). Secondly, apoptosis was accomplished by down-regulation of Bcl-2 and up-regulation of BAX and Caspase-3 by these active compounds. Also, the Pim-1 inhibitory activity of the active hybrids was done, which indicate that compound 3e was the most active with percentage of inhibition 82.27% and IC50 equal 0.11 when compaired to SGI-1776 as a reference standered. In addition, the in silico assessment of ADME properties, all of the strongest compounds are orally bioavailable without blood brain barrier penetration.

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“…Many chalcones have the ability to inhibit tumour proliferation by a variety of mechanisms as inhibition of tubulin 20 , epidermal growth factor receptor (EGFR) 33 , vascular endothelial growth factor receptor-2 (VEGFR-2) 5 , 15 and mitogen-activated protein kinase (MAPK) 29 , 34 .…”

Section: Introductionmentioning

confidence: 99%

Synthesis and biological evaluation of halogenated phenoxychalcones and their corresponding pyrazolines as cytotoxic agents in human breast cancer

Halim

¹

,

Hassan

²

,

Mohamed

³

et al. 2021

Journal of Enzyme Inhibition and Medicinal Chemistry

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Novel halogenated phenoxychalcones 2a–f and their corresponding N -acetylpyrazolines 3a–f were synthesised and evaluated for their anticancer activities against breast cancer cell line (MCF-7) and normal breast cell line (MCF-10a), compared with staurosporine. All compounds showed moderate to good cytotoxic activity when compared to control. Compound 2c was the most active, with IC 50 = 1.52 µM and selectivity index = 15.24. Also, chalcone 2f showed significant cytotoxic activity with IC 50 = 1.87 µM and selectivity index = 11.03. Compound 2c decreased both total mitogen activated protein kinase (p38α MAPK) and phosphorylated enzyme in MCF-7 cells, suggesting its ability to decrease cell proliferation and survival. It also showed the ability to induce ROS in MCF-7 treated cells. Compound 2c exhibited apoptotic behaviour in MCF-7 cells due to cell accumulation in G2/M phase and elevation in late apoptosis 57.78-fold more than control. Docking studies showed that compounds 2c and 2f interact with p38alpha MAPK active sites.

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Isatin-Schiff's base and chalcone hybrids as chemically apoptotic inducers and EGFR inhibitors; design, synthesis, anti-proliferative activities and in silico evaluation

Cited by 49 publications

References 69 publications

Carboxamide appended quinoline moieties as potential anti-proliferative agents, apoptotic inducers and Pim-1 kinase inhibitors

Carboxamide appended quinoline moieties as potential anti-proliferative agents, apoptotic inducers and Pim-1 kinase inhibitors

Carboxamide Appended Quinoline Moieties as Potential Antiproliferative Agents, Apoptotic Inducers and Pim-1 Kinase Inhibitors

Synthesis and biological evaluation of halogenated phenoxychalcones and their corresponding pyrazolines as cytotoxic agents in human breast cancer

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