Design and synthesis of novel uracil-linked Schiff bases as dual histone deacetylase type II/topoisomerase type I inhibitors with apoptotic potential-Reference-Cited by-同舟云学术

Design and synthesis of novel uracil-linked Schiff bases as dual histone deacetylase type II/topoisomerase type I inhibitors with apoptotic potential

Published:2023-06 Issue:11 Volume:15 Page:937-958
ISSN:1756-8919
Container-title:Future Medicinal Chemistry
language:en
Short-container-title:Future Medicinal Chemistry

Author:

El-Kalyoubi Samar¹^ORCID,Elbaramawi Samar S²^ORCID,Eissa Ahmed G²,Al-Ageeli Essam³^ORCID,Hobani Yahya Hasan⁴,El-Sharkawy Aya Ali⁵,Mohamed Hossam Taha⁵⁶,Al-Karmalawy Ahmed A⁷^ORCID,Abulkhair Hamada S⁸⁹^ORCID

Affiliation:

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

2. Department of Medicinal Chemistry, Faculty of Pharmacy, Zagazig University, Zagazig, 44519, Egypt

3. Department of Clinical Biochemistry (Medical Genetics), Faculty of Medicine, Jazan University, Jazan, 82621, Saudi Arabia

4. Medical Laboratory Technology Department, College of Applied Medical Sciences, Jazan University, Jazan, 82621, Saudi Arabia

5. Zoology Department, Faculty of Science, Cairo University, Cairo, 12613, Egypt

6. Faculty of Biotechnology, October University for Modern Sciences & Arts, Giza, 12451, Egypt

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

8. Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Al-Azhar University, Nasr City, 11884, Cairo, Egypt

9. Pharmaceutical Chemistry Department, Faculty of Pharmacy, Horus University-Egypt, International Coastal Road, New Damietta, 34518, Egypt

Abstract

Aim: The previously reported dual histone deacetylase type II (HDAC II) / topoisomerase type I (Topo I) inhibitors suffer pharmacokinetic limitations because of their huge molecular weights. Materials & methods: We report the design and synthesis of a smarter novel set of uracil-linked Schiff bases (19–30) as dual HDAC II/Topo I inhibitors keeping the essential pharmacophoric features. Cytotoxicity of all compounds was assessed against three cancer cell lines. Studies of their effects on the apoptotic BAX and antiapoptotic BCL2 genes, molecular docking studies, and absorption, distribution, metabolism and excretion studies were conducted. Results: Compounds 22, 25 and 30 exhibited significant activities. The bromophenyl derivative 22 displayed the best selectivity index, with IC50values against HDAC II and Topo I of 1.12 and 13.44 μM, respectively. Conclusion: Compound 22 could be considered a lead HDAC II/Topo I inhibitor.

Publisher

Future Science Ltd

Subject

Drug Discovery,Pharmacology,Molecular Medicine

Link

https://www.future-science.com/doi/pdf/10.4155/fmc-2023-0112

Reference84 articles.

1. American Cancer Society. Cancer facts and figures 2022 (2023). www.cancer.org/research/cancer-facts-statistics/all-cancer-facts-figures/cancer-facts-figures-2022.html#:∼:text=Estimatednumbersofnewcancer,incidence%2Cmortality%2Candsurvivalstatistics

2. A view on drug resistance in cancer

3. New quinoxalin‐2(1 H )‐one‐derived VEGFR‐2 inhibitors: Design, synthesis, in vitro anticancer evaluations, in silico ADMET, and docking studies

4. Ligand-Based Design on the Dog-Bone-Shaped BIBR1532 Pharmacophoric Features and Synthesis of Novel Analogues as Promising Telomerase Inhibitors with In Vitro and In Vivo Evaluations

5. Dual Inhibitors of Human DNA Topoisomerase II and Other Cancer-Related Targets

Cited by 5 articles. 订阅此论文施引文献订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献

1. Understanding Cancer’s Defense against Topoisomerase-Active Drugs: A Comprehensive Review;Cancers;2024-02-06

2. Rational design and eco-friendly one-pot multicomponent synthesis of novel ethylidenehydrazineylthiazol-4(5H)-ones as potential apoptotic inducers targeting wild and mutant EGFR-TK in triple negative breast cancer;Bioorganic Chemistry;2024-01

3. Novel benzochromenes: design, synthesis, cytotoxicity, molecular docking and mechanistic investigations;Future Medicinal Chemistry;2024-01

4. Molecular overlay-guided design of new CDK2 inhibitor thiazepinopurines: Synthesis, anticancer, and mechanistic investigations;Bioorganic Chemistry;2023-11

5. Design and synthesis of novel pyrazolopyrimidine candidates as promising EGFR-T790M inhibitors and apoptosis inducers;Future Medicinal Chemistry;2023-10