Design and synthesis of novel pyrazolopyrimidine candidates as promising EGFR-T790M inhibitors and apoptosis inducers

Ahmed A. Gaber; Marwa Sharaky; Ayman Abo Elmaaty; Mohamed M. Hammouda; Ahmed A.E. Mourad; Samy Y. Elkhawaga; Mahmoud Mohamed Mokhtar; Amr S. Abouzied; Mai A.E. Mourad; Ahmed A. Al-Karmalawy

doi:10.4155/fmc-2023-0156

Design and synthesis of novel pyrazolopyrimidine candidates as promising EGFR-T790M inhibitors and apoptosis inducers

Ahmed A. Gaber
, Marwa Sharaky
, Ayman Abo Elmaaty
, Mohamed M. Hammouda
, Ahmed A.E. Mourad
, Samy Y. Elkhawaga
, Mahmoud Mohamed Mokhtar
, Amr S. Abouzied
, Mai A.E. Mourad
, Ahmed A. Al-Karmalawy

Chemistry

Al-Azhar University
Cairo University
Port Said University
University of Hail
National Organization for Drug Control and Research
Horus University - Egypt
Al-Ahram Canadian University

Research output: Contribution to journal › Article › peer-review

10 Scopus citations

Abstract

Aim: Our objective was to design and synthesize a new range of pyrazolopyrimidines while maintaining the key pharmacophoric features of EGFR tyrosine kinase inhibitors. Materials & methods: Percentage inhibition in 14 human cancer cell lines and IC50 values were recorded. Compounds 6c, 7e and 7f were examined against both wild and mutant (T790M) EGFR subtypes. Apoptosis markers, cell cycle arrest, apoptosis assay and molecular docking were performed. Results: Compounds 6c, 7e and 7f demonstrated superior inhibitory potentials against wild and mutant (T790M) EGFR subtypes. A molecular docking study showed that compounds 6c and 7e had the best fit. Conclusion: The designed candidates demonstrated superior inhibitory potential as promising EGFR-T790M inhibitors that agrees with the proposed rationale.

Original language	English
Pages (from-to)	1773-1790
Number of pages	18
Journal	Future Medicinal Chemistry
Volume	15
Issue number	19
DOIs	https://doi.org/10.4155/fmc-2023-0156
State	Published - 1 Oct 2023

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

EGFR TKIs
EGFR-T790M
EGFR-WT
apoptosis markers
pyrazolopyrimidine

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10.4155/fmc-2023-0156

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Gaber, A. A., Sharaky, M., Elmaaty, A. A., Hammouda, M. M., Mourad, A. A. E., Elkhawaga, S. Y., Mokhtar, M. M., Abouzied, A. S., Mourad, M. A. E., & Al-Karmalawy, A. A. (2023). Design and synthesis of novel pyrazolopyrimidine candidates as promising EGFR-T790M inhibitors and apoptosis inducers. Future Medicinal Chemistry, 15(19), 1773-1790. https://doi.org/10.4155/fmc-2023-0156

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title = "Design and synthesis of novel pyrazolopyrimidine candidates as promising EGFR-T790M inhibitors and apoptosis inducers",

abstract = "Aim: Our objective was to design and synthesize a new range of pyrazolopyrimidines while maintaining the key pharmacophoric features of EGFR tyrosine kinase inhibitors. Materials \& methods: Percentage inhibition in 14 human cancer cell lines and IC50 values were recorded. Compounds 6c, 7e and 7f were examined against both wild and mutant (T790M) EGFR subtypes. Apoptosis markers, cell cycle arrest, apoptosis assay and molecular docking were performed. Results: Compounds 6c, 7e and 7f demonstrated superior inhibitory potentials against wild and mutant (T790M) EGFR subtypes. A molecular docking study showed that compounds 6c and 7e had the best fit. Conclusion: The designed candidates demonstrated superior inhibitory potential as promising EGFR-T790M inhibitors that agrees with the proposed rationale.",

keywords = "EGFR TKIs, EGFR-T790M, EGFR-WT, apoptosis markers, pyrazolopyrimidine",

author = "Gaber, \{Ahmed A.\} and Marwa Sharaky and Elmaaty, \{Ayman Abo\} and Hammouda, \{Mohamed M.\} and Mourad, \{Ahmed A.E.\} and Elkhawaga, \{Samy Y.\} and Mokhtar, \{Mahmoud Mohamed\} and Abouzied, \{Amr S.\} and Mourad, \{Mai A.E.\} and Al-Karmalawy, \{Ahmed A.\}",

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doi = "10.4155/fmc-2023-0156",

language = "English",

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T1 - Design and synthesis of novel pyrazolopyrimidine candidates as promising EGFR-T790M inhibitors and apoptosis inducers

AU - Gaber, Ahmed A.

AU - Sharaky, Marwa

AU - Elmaaty, Ayman Abo

AU - Hammouda, Mohamed M.

AU - Mourad, Ahmed A.E.

AU - Elkhawaga, Samy Y.

AU - Mokhtar, Mahmoud Mohamed

AU - Abouzied, Amr S.

AU - Mourad, Mai A.E.

AU - Al-Karmalawy, Ahmed A.

PY - 2023/10/1

Y1 - 2023/10/1

N2 - Aim: Our objective was to design and synthesize a new range of pyrazolopyrimidines while maintaining the key pharmacophoric features of EGFR tyrosine kinase inhibitors. Materials & methods: Percentage inhibition in 14 human cancer cell lines and IC50 values were recorded. Compounds 6c, 7e and 7f were examined against both wild and mutant (T790M) EGFR subtypes. Apoptosis markers, cell cycle arrest, apoptosis assay and molecular docking were performed. Results: Compounds 6c, 7e and 7f demonstrated superior inhibitory potentials against wild and mutant (T790M) EGFR subtypes. A molecular docking study showed that compounds 6c and 7e had the best fit. Conclusion: The designed candidates demonstrated superior inhibitory potential as promising EGFR-T790M inhibitors that agrees with the proposed rationale.

AB - Aim: Our objective was to design and synthesize a new range of pyrazolopyrimidines while maintaining the key pharmacophoric features of EGFR tyrosine kinase inhibitors. Materials & methods: Percentage inhibition in 14 human cancer cell lines and IC50 values were recorded. Compounds 6c, 7e and 7f were examined against both wild and mutant (T790M) EGFR subtypes. Apoptosis markers, cell cycle arrest, apoptosis assay and molecular docking were performed. Results: Compounds 6c, 7e and 7f demonstrated superior inhibitory potentials against wild and mutant (T790M) EGFR subtypes. A molecular docking study showed that compounds 6c and 7e had the best fit. Conclusion: The designed candidates demonstrated superior inhibitory potential as promising EGFR-T790M inhibitors that agrees with the proposed rationale.

KW - EGFR TKIs

KW - EGFR-T790M

KW - EGFR-WT

KW - apoptosis markers

KW - pyrazolopyrimidine

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M3 - Article

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SN - 1756-8919

VL - 15

SP - 1773

EP - 1790

JO - Future Medicinal Chemistry

JF - Future Medicinal Chemistry

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ER -

Design and synthesis of novel pyrazolopyrimidine candidates as promising EGFR-T790M inhibitors and apoptosis inducers

Abstract

UN SDGs

Keywords

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