Design and synthesis of novel pyrazolopyrimidine candidates as promising EGFR-T790M inhibitors and apoptosis inducers-Reference-Cited by-同舟云学术

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

Published:2023-10 Issue:19 Volume:15 Page:1773-1790
ISSN:1756-8919
Container-title:Future Medicinal Chemistry
language:en
Short-container-title:Future Medicinal Chemistry

Author:

Gaber Ahmed A¹,Sharaky Marwa²,Elmaaty Ayman Abo³,Hammouda Mohamed M⁴⁵,Mourad Ahmed AE⁶,Elkhawaga Samy Y⁷,Mokhtar Mahmoud Mohamed⁷,Abouzied Amr S⁸⁹,Mourad Mai AE³,Al-Karmalawy Ahmed A¹⁰¹¹^ORCID

Affiliation:

1. Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo, 11884, Egypt

2. Pharmacology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, Egypt

3. Medicinal Chemistry Department, Faculty of Pharmacy, Port Said University, Port Said, 42511, Egypt

4. Department of Chemistry, College of Science & Humanities in Al-Kharj, Prince Sattam bin Abdulaziz University, Al-Kharj, 11942, Saudi Arabia

5. Department of Chemistry, Faculty of Science, Mansoura University, Mansoura, 35516, Egypt

6. Pharmacology & Toxicology Department, Faculty of Pharmacy, Port Said University, Port Said, 42511, Egypt

7. Biochemistry & Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City, Cairo, 11231, Egypt

8. Department of Pharmaceutical Chemistry, College of Pharmacy, University of Hail, Hail, 81442, Saudi Arabia

9. Department of Pharmaceutical Chemistry, National Organization for Drug Control & Research, Giza, 12553, Egypt

10. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Horus University-Egypt, New Damietta 34518, Egypt.

11. Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ahram Canadian University, 6th of October City, Giza, 12566, Egypt

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.

Funder

Prince Sattam bin Abdulaziz University

Publisher

Future Science Ltd

Subject

Drug Discovery,Pharmacology,Molecular Medicine

Link

https://www.future-science.com/doi/pdf/10.4155/fmc-2023-0156

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