New thiouracil derivatives as histone deacetylase inhibitors and apoptosis inducers: design, synthesis and anticancer evaluation-Reference-Cited by-同舟云学术

New thiouracil derivatives as histone deacetylase inhibitors and apoptosis inducers: design, synthesis and anticancer evaluation

Published:2023-06 Issue:12 Volume:15 Page:1019-1035
ISSN:1756-8919
Container-title:Future Medicinal Chemistry
language:en
Short-container-title:Future Medicinal Chemistry

Author:

Elbatrawy Omnia R¹^ORCID,El Deeb Moshira A¹^ORCID,Hagras Mohamed²^ORCID,Agili Fatimah³^ORCID,Hegazy Maghawry⁴,El-Husseiny Ahmed A⁴⁵,Elkady Mohamed A⁴^ORCID,Eissa Ibrahim H⁶^ORCID,El-Kalyoubi Samar⁷^ORCID

Affiliation:

1. Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, 11754, Egypt

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

3. Chemistry Department, Faculty of Science (Female Section), Jazan University, Jazan, 82621, Saudi Arabia

4. Biochemistry & Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo, 11884, Egypt

5. Department of Biochemistry, Faculty of Pharmacy, Egyptian Russian University, Badr City, 11829, Cairo, Egypt

6. Pharmaceutical Medicinal Chemistry & Drug Design Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo, 11884, Egypt

7. Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Port Said University, 42511, Port Said, Egypt

Abstract

Background: Histone deacetylase (HDAC) inhibitors have good contributions in cancer management. Aim: To introduce new active HDAC inhibitors. Methods: Design and synthesis of 16 thiouracil derivatives with deep biological and computational investigation. Results: Compounds 7a, 7c, 7d, 7e, 8a and 8f showed the highest antiproliferative effects against MCF7, HepG2 and HCT116 cell lines. Compound 7e exhibited the highest activities against HDAC1 and HDAC4. Compound 7e arrested the cell cycle of HCT116 cells at G0–G1 with significant apoptotic effect. In addition, treatment with compound 7e was associated with a significant increase in the levels of caspase-3 and caspase-8. The docking studies gave good insight about the binding patterns of the synthesized compounds against HDAC1. Conclusion: Compound 7e has a promising anticancer activity targeting HDAC.

Publisher

Future Science Ltd

Subject

Drug Discovery,Pharmacology,Molecular Medicine

Link

https://www.future-science.com/doi/pdf/10.4155/fmc-2023-0106

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