Camellia sinensis phytochemical profiling, drug-likeness, and antibacterial activity against gram-positive and gram-negative bacteria: in vitro and in silico insights.

Abstract

Background: Camellia sinensis extracts have a rich phytochemical profile and therapeutic properties. The plant contains bioactive compounds, such as catechins, flavonoids, and phenolic acids, which are associated with various health benefits, including antioxidant, anti-inflammatory, and anticancer activities.

Aim: To investigate the bioactive potential of a Camellia sinensis extract, particularly its antibacterial activity against Gram-positive and Gram-negative bacteria and its drug-like properties.

Method: Phenolic compounds in C. sinensis extract were identified and quantified using high-performance liquid chromatography (HPLC). Its antibacterial activity was assessed against both Gram-positive (Staphylococcus aureus) and Gram-negative bacteria (Pseudomonas aeruginosa and Escherichia coli). Drug-likeness, toxicity, and molecular properties of the identified compounds were investigated using computational approaches. Additionally, binding affinities of selected compounds were predicted via molecular docking to elucidate potential antibacterial mechanisms.

Results: HPLC identified caffeic acid (10.32 mg/g), epigallocatechin gallate (EGCG, 8.74 mg/g), syringic acid (6.21 mg/g), and quercetin (15.29 mg/g). Antibacterial activity testing revealed inhibition zones ranging from 10.62 mm for Gram-negative E. coli to 18.65 mm for Gram-positive S. aureus, comparable to gentamicin (19.42 mm). Molecular docking predicted that EGCG (-9.8 kcal/mol) was the most potent compound against Gram-negative P. aeruginosa RNase PH, followed by quercetin (-8.7 kcal/mol). Drug-likeness modeling indicated favorable profiles for most compounds, although EGCG violated Lipinski's rule due to its molecular weight (458.4 g/mol). Density Functional Theory analysis revealed significant variations in electronic properties among the selected compounds, with quercetin exhibiting the smallest HOMO-LUMO gap (2.31 eV), suggesting high reactivity. MD simulations confirmed the stability of the EGCG-protein complex, with RMSD values (∼2.5-3.0 Å), reduced RMSF at key residues, and stable Rg (∼18-20 Å).

Discussion: The results highlight that C. sinensis is a valuable source of bioactive phenolic compounds with promising antibacterial properties against both Gram-positive and Gram-negative bacteria, particularly EGCG. Quercetin, the most abundant compound, showed better chemical stability (higher HOMO-LUMO gap), but its lower binding affinity suggests that EGCG is a more effective therapeutic candidate. Moreover, the antibacterial activity of these compounds positions them as potential alternatives to conventional antibiotics. Future research should focus on in vivo validation, structure-activity optimization, and formulation development to improve bioavailability and clinical applicability.