Journal article
Thiophene Derivative‐Loaded Nanoparticles Mediate Anticancer Activity Through the Inhibition of Kinases and Microtubule Assembly
Advanced therapeutics, Vol.4(7), pp.2100058-n/a
07/2021
DOI: 10.1002/adtp.202100058
PMCID: PMC8372755
PMID: 34423112
Abstract
Different tetrahydrobenzo[b]thiophene derivatives are explored as new tubulin polymerization destabilizers to arrest tumor cell mitosis. A series of compounds incorporating the tetrahydrobenzo[b]thiophene scaffold are synthesized, and their biological activities are investigated. The cytotoxicity of each of the synthesized compounds is assessed against a range of cell lines. Specifically, the benzyl urea tetrahydrobenzo[b]thiophene derivative, 1-benzyl-3-(3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)urea (BU17), is identified as the most potent compound with broad-spectrum antitumor activity against several cancer cell lines. The potential mechanism(s) of action are investigated where dose-dependent G2/M accumulation and A549 cell cycle arrest are detected. Additionally, A549 cells treated with BU17 express enhanced levels of caspase 3 and 9, indicating the induction of apoptosis. Furthermore, it is found that BU17 inhibits WEE1 kinase and targets tubulin by blocking its polymerization. BU17 is also formulated into PLGA nanoparticles, and it is demonstrated that BU17-loaded nanoparticles can significantly enhance antitumor activity compared to the soluble counterpart.
Details
- Title: Subtitle
- Thiophene Derivative‐Loaded Nanoparticles Mediate Anticancer Activity Through the Inhibition of Kinases and Microtubule Assembly
- Creators
- Somaya A Abdel‐Rahman - Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy University of Iowa Iowa City IA 52242 USA, Department of Medicinal Chemistry, Faculty of Pharmacy Mansoura University Mansoura 35516 EgyptEmad I Wafa - Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy University of Iowa Iowa City IA 52242 USAKareem Ebeid - Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy University of Iowa Iowa City IA 52242 USA, Department of Pharmaceutics, Faculty of Pharmacy Minia University Minia 61519 Egypt, Department of Pharmaceutics, Faculty of Pharmacy Deraya University New Minia City Minia 61519 EgyptSean M Geary - Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy University of Iowa Iowa City IA 52242 USAYoussef W Naguib - Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy University of Iowa Iowa City IA 52242 USA, Department of Pharmaceutics, Faculty of Pharmacy Minia University Minia 61519 Egypt, Department of Pharmaceutics, Faculty of Pharmacy Deraya University New Minia City Minia 61519 EgyptAshraf K El‐Damasy - Department of Medicinal Chemistry, Faculty of Pharmacy Mansoura University Mansoura 35516 EgyptAliasger K Salem - Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy University of Iowa Iowa City IA 52242 USA, Holden Comprehensive Cancer Center University of Iowa Iowa City IA 52242 USA
- Resource Type
- Journal article
- Publication Details
- Advanced therapeutics, Vol.4(7), pp.2100058-n/a
- DOI
- 10.1002/adtp.202100058
- PMID
- 34423112
- PMCID
- PMC8372755
- NLM abbreviation
- Adv Ther (Weinh)
- ISSN
- 2366-3987
- eISSN
- 2366-3987
- Language
- English
- Date published
- 07/2021
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Pharmaceutical Sciences and Experimental Therapeutics; Craniofacial Anomalies Research Center; Dental Research; Chemical and Biochemical Engineering
- Record Identifier
- 9984216585902771
Metrics
8 Record Views