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

Abstract

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 (IC 50 =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.

The antimicrobial activity of tea tree oil (Melaleuca alternifolia) and its metal nanoparticles in oral bacteria

“…In addition, the phytochemicals attached around the central metal nucleus may have active functional groups that are not exposed outwardly to allow biological interactions to take place, hence limiting the therapeutic activity of the Green-NPs ( Saptarshi, Duschl & Lopata, 2013 ). In support of this, we reported earlier that the functional groups might lend a role in repelling or attracting biological targets, which could be useful in precision medicine ( Mohammed et al, 2023b ), but concurrently, the lack of control over the specific phytochemicals and exposed functional groups around the surface of the NP may contribute to increasingly inactive NPs. Clumped NPs clearly would reduce biological reactivity due to the reduced surface area ratio, reducing the biological interaction interfaces.…”

Design rules applied to silver nanoparticles synthesis: A practical example of machine learning application.

“…It can effectively handle diverse datasets, capture nonlinear relationships, and make predictions [86] , [87] . By utilizing ML algorithms, researchers can consider multiple synthesis parameters and their interactions, enabling accurate predictions of AgNP properties based on given synthesis parameters, helping to guide and prioritize experimental efforts [88] . It becomes possible to explore virtually the effects of different synthesis conditions combinations without conducting numerous time-consuming and costly experiments [89] .…”

Myco-fabricated silver nanoparticle by novel soil fungi from Saudi Arabian desert and antimicrobial mechanism

“…With the emergence of antimicrobial resistance, the need for alternative antimicrobial agents to replace the conventional ones enhanced researchers to develop AgNPs as one of the good options for microbial mitigation. Previous studies have approved the ability of AgNPs as antimicrobial agents with significant effects against some multidrug- resistant bacteria 12 , 17 , 18 . The unique and wide range of AgNPs applications are the factors that led to the development of various fabrication methods for efficient and safe usage 19 – 21 .…”