Multitargeted molecular modelling of alginic acid modified with 4-aminophenol dopped with silver nanoparticles as a potent cytotoxic agent

Haneen A Mahmoud; Emadeldin M Kamel; Ayman M Mahmoud; Reem S Alruhaimi; Ali M El-Zanaty; Hanafy M Abd El-Salam; Omayma F Abdel-Gawad

doi:10.1016/j.heliyon.2023.e17106

Multitargeted molecular modelling of alginic acid modified with 4-aminophenol dopped with silver nanoparticles as a potent cytotoxic agent

Heliyon. 2023 Jun 14;9(6):e17106. doi: 10.1016/j.heliyon.2023.e17106. eCollection 2023 Jun.

Authors

Haneen A Mahmoud¹, Emadeldin M Kamel¹, Ayman M Mahmoud^{2

3}, Reem S Alruhaimi⁴, Ali M El-Zanaty¹, Hanafy M Abd El-Salam¹, Omayma F Abdel-Gawad¹

Affiliations

¹ Chemistry Department, Faculty of Science, Beni-Suef University, Beni-Suef, 62514, Egypt.
² Physiology Division, Zoology Department, Faculty of Science, Beni-Suef University, Beni-Suef, 62514, Egypt.
³ Department of Life Sciences, Faculty of Science and Engineering, Manchester Metropolitan University, Manchester, M1 5GD, UK.
⁴ Department of Biology, College of Science, Princess Nourah bint Abdulrahman University, Riyadh, 11671, Saudi Arabia.

Abstract

The activity of alginic acid as a cytotoxic agent was improved by structure modification using 4-aminophenol (4-AP) through condensation and polymerization processes. Then, silver nanoparticles were employed through doping to further enhance the cytotoxic activity of the modified polymer. The structure of the prepared materials was characterized by FT-IR, ¹HNMR, UV spectroscopy, X-ray diffraction, and electron microscopy, and the thermal behavior of all synthesized materials was intensively studied. The cytotoxicity of the prepared compounds against cell lines of human hepatocellular (HepG-2) and lung (A-549) carcinomas was investigated. Alginic acid modified with 4-AP (Alg-4-AP₃) showed the highest activity against HepG-2 and A-549 among all tested materials with IC₅₀ values of 3.0 ± 0.19 μg/mL and 3.63 ± 0.23 μg/mL, respectively. Multitargeted molecular docking was employed to explore the binding modes of our compounds with the receptors EGFR, HER2, and VEGFR 2. The results revealed the inhibitory activity of our tested compounds against the proposed protein receptors, findings coincided with the in vitro results. In conclusion, the modification of alginic acid with 4-AP improved its cytotoxic activity against HepG-2 and A-549 cancer cells. In addition, doping the new materials with silver nanoparticles (AgNPs) further enhanced the cytotoxic activity.

Keywords: 4-Aminophenol; Alginic acid; Cytotoxicity; Silver nanoparticles.