Design and Synthesis of Newly Synthesized Acrylamide Derivatives as Potential Chemotherapeutic Agents against MCF-7 Breast Cancer Cell Line Lodged on PEGylated Bilosomal Nano-Vesicles for Improving Cytotoxic Activity

Islam Zaki; Reham A I Abou-Elkhair; Ali H Abu Almaaty; Ola A Abu Ali; Eman Fayad; Ahmed Gaafar Ahmed Gaafar; Mohamed Y Zakaria

doi:10.3390/ph14101021

Design and Synthesis of Newly Synthesized Acrylamide Derivatives as Potential Chemotherapeutic Agents against MCF-7 Breast Cancer Cell Line Lodged on PEGylated Bilosomal Nano-Vesicles for Improving Cytotoxic Activity

Pharmaceuticals (Basel). 2021 Oct 4;14(10):1021. doi: 10.3390/ph14101021.

Authors

Islam Zaki¹, Reham A I Abou-Elkhair², Ali H Abu Almaaty³, Ola A Abu Ali⁴, Eman Fayad⁵, Ahmed Gaafar Ahmed Gaafar⁶, Mohamed Y Zakaria⁷

Affiliations

¹ Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Port Said University, Port Said 42526, Egypt.
² Applied Nucleic Acids Research Center & Chemistry Department, Faculty of Science, Zagazig University, Zagazig 44523, Egypt.
³ Zoology Department, Faculty of Science, Port Said University, Port Said 42526, Egypt.
⁴ Chemistry Department, College of Science, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.
⁵ Biotechnology Department, Faculty of Sciences, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.
⁶ Pharmacology and Toxicology Department, Faculty of Pharmacy, Port Said University, Port Said 42526, Egypt.
⁷ Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Port Said University, Port Said 42526, Egypt.

Abstract

Cancer is a multifaceted disease. With the development of multi drug resistance, the need for the arousal of novel targets in order to avoid these drawbacks increased. A new series of acrylamide derivatives was synthesized from starting material 4-(furan-2-ylmethylene)-2-(3,4,5-trimethoxyphenyl)oxazol-5(4H)-one (1), and they are evaluated for their inhibitory activity against β-tubulin polymerization. The target molecules 2-5 d were screened for their cytotoxic activity against breast cancer MCF-7 cell line. The results of cytotoxicity screening revealed that compounds 4e and 5d showed good cytotoxic profile against MCF-7 cells. Compounds 4e produced significant reduction in cellular tubulin with excellent β-tubulin polymerization inhibition activity. In addition, compound 4e exhibited cytotoxic activity against MCF-7 cells by cell cycle arrest at pre-G1 and G2/M phases, as shown by DNA flow cytometry assay. Aiming to enhance the limited aqueous solubility and, hence, poor oral bioavailability of the prepared lead acrylamide molecule, 4e-charged PEGylated bilosomes were successfully fabricated via thin film hydration techniques as an attempt to improve these pitfalls. 2³ full factorial designs were manipulated to examine the influence of formulation variables: types of bile salt including either sodium deoxy cholate (SDC) or sodium tauro cholate (STC), amount of bile salt (15 mg or 30 mg) and amount of DSPE-mPEG-2000 amount (25 mg or 50 mg) on the characteristics of the nanosystem. The F7 formula of entrapment efficiency (E.E% = 100 ± 5.6%), particle size (PS = 280.3 ± 15.4 nm) and zeta potential (ZP = -22.5 ± 3.4 mv) was picked as an optimum formula with a desirability value of 0.868. Moreover, prominent enhancement was observed at the compound's cytotoxic activity (IC₅₀ = 0.75 ± 0.03 µM) instead of (IC₅₀ = 2.11 ± 0.19 µM) for the unformulated 4e after being included in the nano-PEGylated bilosomal system.

Keywords: PEGylated bilosomes; acrylamide; annexin; aqueous solubility and optimization; cell cycle analysis; tubulin.

Grants and funding

TURSP-2020/220/Taif University researchers supporting project number (TURSP-2020/220) Taif University, Taif, Saudi Arabia.