Phytochemical Characterization, Antimicrobial Activity, Pharmacokinetic, in silico Molecular Docking and Interaction Analysis of Ajwa (Phoenix dactylifera L.) Palm Date Seeds

Background: There is growing evidence that antibiotic resistance is increasing. As a result, the efficacy of these antibiotics is gradually declining. This poses a serious health risk in terms of treatment strategies. Therefore, the scientific community is continuously putting all efforts into looking for novel and green therapeutics to overcome the problem of antibiotic resistance. Objectives: The aim of this study is to investigate the chemical composition of the methanolic extracts obtained from Phoenix dactylifera seeds, known agricultural waste, to identify new bioactive compounds and to examine the antibacterial and antifungal potentials. Materials and Methods: Phytochemical profiling was performed by the gas chromatography-mass spectrometry (GC-MS) technique. For the antibacterial activity of the methanolic extract, 12 microorganisms were selected, including eight bacteria (Escherichia coli ATCC 35218, Pseudomonas aeruginosa ATCC 27853, Enterobacter cloacae, Enterococcus faecium, Staphylococcus hominis, Staphylococcus aureus, Staphylococcus epidermidis, and Klebsiella pneumoniae ATCC 27736) and four Candida species (C. albicans ATCC 10231, C. tropicalis ATCC 1362, C. utilis ATCC 9255, and C. guilliermondii ATCC 6260). The antimicrobial activity of the plant extract was supported by in silico molecular docking analysis. Results: The obtained results from the GC-MS technique revealed the presence of 51 compounds, of which 6-octadecenoic acid (Z) was identified as the major component. The tested extract exhibited the highest zone of inhibition against S. aureus (growth inhibition zone 14.66 +/- 0.57 mm). In addition, minimal inhibitory concentration (MIC) and minimal bactericidal concentration values obtained against S. aureus were 1.4 and 5.6 mg/mL, respectively. Regarding the antifungal assay, C. albicans was the most sensitive one to the extract among all the tested Candida strains (14.33 mm) (MIC: 1.4 mg/mL, minimal fungicidal concentration (MFC): 11.2 mg/mL). The binding free energies and root mean square deviation values obtained from the interaction of phytochemicals with two different target receptors (1JIJ and 2QZW for TyrRS from S. aureus and aspartic proteinase from C. albicans) were also determined. Ergost-5-en-3-ol, (3beta) established hydrogen, electrostatic, alkyl, and pi-alkyl interactions with five different amino acid residues (Asp40, Asp80, Pro53, His50, and Phe54) located at the TyrRS receptor of S. aureus. On the other hand, hexadecanoic acid and methyl ester established hydrogen, electrostatic, pi-sigma, and alkyl interactions with five different amino acid residues (Thr222, Asp86, Asp218, Tyr84, and Ile123) located at the aspartic proteinase receptor of C. albicans. These interactions contributed to the stability of the complex and, hence, to the biological activity of the P. dactylifera compounds. Conclusion: Our results highlighted that methanolic extract from date seeds can be a natural source of chemical compounds with promising antibacterial and antifungal activities, as demonstrated using both in vitro and in silico approaches.