Synthesis of novel coumarin-triazole hybrids and first evaluation of the 4-phenyl substituted hybrid loaded PLGA nanoparticles delivery system to the anticancer activity.

Autor: Arvas B; Department of Chemistry, Faculty of Arts & Science, Yildiz Technical University, Istanbul, Turkey., Ucar B; Department of Biomedical Engineering, Faculty of Engineering and Architecture, Istanbul Arel University, Istanbul, Turkey., Acar T; Department of Bioengineering, Faculty of Chemical and Metallurgical Engineering, Yildiz Technical University, Istanbul, Turkey., Varli HS; Science and Technology Application and Research Center, Yildiz Technical University, Istanbul, Turkey.; Department of Molecular Biology and Genetics, Faculty of Arts & Science, Yildiz Technical University, Istanbul, Turkey., Arvas MB; Department of Chemistry, Faculty of Science, Istanbul University, Istanbul, Turkey., Aydogan F; Department of Chemistry, Faculty of Arts & Science, Yildiz Technical University, Istanbul, Turkey., Yolacan C; Department of Chemistry, Faculty of Arts & Science, Yildiz Technical University, Istanbul, Turkey.
Jazyk: angličtina
Zdroj: Nanotechnology [Nanotechnology] 2024 May 07; Vol. 35 (30). Date of Electronic Publication: 2024 May 07.
DOI: 10.1088/1361-6528/ad403e
Abstrakt: Despite the discovery of many chemotherapeutic drugs that prevent uncontrolled cell division processes in the last century, many studies are still being carried out to develop drugs with higher anticancer efficacy and lower level of side effects. Herein, we designed, synthesized, and characterized six novel coumarin-triazole hybrids, and evaluated for anticancer activity of the one with the highest potential against the breast cancer cell line, MCF-7 and human cervical cancer cell line, human cervical adenocarcinoma (HeLa). Compound 21 which was the coumarin derivative including phenyl substituent with the lowest IC50 value displayed the highest cytotoxicity against the studied cancer cell line. Furthermore, the potential use of poly (lactic-co-glycolic acid) nanoparticles (PLGA NPs) prepared by the emulsifying solvent evaporation method as a platform for a drug delivery system was studied on a selected coumarin derivative 21 . This coumarin derivative - loaded PLGA NPs were produced with an average size of 225.90 ± 2.96 nm, -16.90 ± 0.85 mV zeta potential, and 4.12 ± 0.90% drug loading capacity. The obtained 21 -loaded PLGA nanoparticles were analyzed spectroscopically and microscopically with FT-IR, UV-vis, and scanning electron microscopy as well as thermogravimetric analysis, Raman, and x-ray diffraction. The in vitro release of 21 from the nanoparticles exhibited a controlled release profile just over one month following a burst release in the initial six hours and in addition to this a total release ratio of %50 and %85 were obtained at pH 7.4 and 5.5, respectively. 21 -loaded PLGA nanoparticles displayed remarkably effective anticancer activity than 21 . The IC50 values were determined as IC 50 ( 21 -loaded PLGA nanoparticles): 0.42 ± 0.01 mg ml -1 and IC 50 (free 21 molecule): 5.74 ± 3.82 mg ml -1 against MCF-7 cells, and as IC 50 ( 21 -loaded PLGA nanoparticles): 0.77 ± 0.12 mg ml -1 and IC 50 (free 21 molecule): 1.32 ± 0.31 mg ml -1 against HeLa cells after the incubation period of 24 h. Our findings indicated that triazole-substituted coumarins may be used as an anticancer agent by integrating them into a polymeric drug delivery system providing improved drug loading and effective controlled drug release.
(Creative Commons Attribution license.)
Databáze: MEDLINE
Externí odkaz: