In silico Prediction of Malvaviscus arboreus Metabolites and Green Synthesis of Silver Nanoparticles - Opportunities for Safer Anti-Bacterial and Anti-Cancer Precision Medicine

Int J Nanomedicine. 2023 Apr 26:18:2141-2162. doi: 10.2147/IJN.S400195. eCollection 2023.

Abstract

Introduction: Biogenic silver nanoparticles (AgNPs) may be a feasible therapeutic option in the research and development towards selectively targeting specific cancers and microbial infections, lending a role in precision medicine. In-silico methods are a viable strategy to aid in drug discovery by identifying lead plant bioactive molecules for further wet lab and animal experiments.

Methods: Green synthesis of M-AgNPs was performed using the aqueous extract from the Malvaviscus arboreus leaves, characterized using UV spectroscopy, FTIR, TEM, DLS, and EDS. In addition, Ampicillin conjugated M-AgNPs were also synthesized. The cytotoxic potential of the M-AgNPs was evaluated using the MTT assay on MDA-MB 231, MCF10A, and HCT116 cancer cell lines. The antimicrobial effects were determined using the agar well diffusion assay on methicillin-resistant S. aureus (MRSA) and S. mutans, E. coli, and Klebsiella pneumoniae. Additionally, LC-MS was used to identify the phytometabolites, and in silico techniques were applied to determine the pharmacodynamic and pharmacokinetic profiles of the identified metabolites.

Results: Spherical M-AgNPs were successfully biosynthesized with a mean diameter of 21.8 nm and were active on all tested bacteria. Conjugation with ampicillin increased the susceptibility of the bacteria. These antibacterial effects were most predominant in Staphylococcus aureus (p < 0.0001). M-AgNPs had potent cytotoxic activity against the colon cancer cell line (IC50=29.5 μg/mL). In addition, four secondary metabolites were identified, Astragalin, 4-hydroxyphenyl acetic acid, Caffeic acid, and Vernolic acid. In silico studies identified Astragalin as the most active antibacterial and anti-cancer metabolite, binding strongly to the carbonic anhydrase IX enzyme with a comparatively higher number of residual interactions.

Discussion: Synthesis of green AgNPs presents a new opportunity in the field of precision medicine, the concept centered on the biochemical properties and biological effects of the functional groups present in the plant metabolites used for reduction and capping. M-AgNPs may be useful in treating colon carcinoma and MRSA infections. Astragalin appears to be the optimal and safe lead for further anti-cancer and anti-microbial drug development.

Keywords: Astragalin; LC-MS; biogenic AgNPs; biological activity.

MeSH terms

  • Ampicillin
  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Bacteria
  • Colonic Neoplasms*
  • Escherichia coli
  • Metal Nanoparticles*
  • Methicillin-Resistant Staphylococcus aureus*
  • Microbial Sensitivity Tests
  • Plant Extracts / pharmacology
  • Precision Medicine
  • Silver / pharmacology

Substances

  • Silver
  • Ampicillin
  • Anti-Bacterial Agents
  • Plant Extracts

Grants and funding

This work was funded by the Deanship of Scientific Research at Princess Nourah bint Abdulrahman University, through the Research Groups Program Grant no. (RGP-1443-0041).