Phytochemical profiling, spectroscopic identification of active compounds, and mechanism of the anticandidal properties of Datura stramonium L. using SwissADMET prediction and molecular docking analysis.

Background: Datura stramonium L., a wild-growing herb, has been traditionally used to treat various ailments, including toothache, asthma, rheumatism, epilepsy, and alopecia. Scientific evidence supports its anticancer, anti-inflammatory, anti-asthmatic, anticholinergic, antifungal, and antibacterial properties.

Aim: This study aimed to isolate, characterize, and identify the most potent anticandidal compounds inhibiting the growth of Candida spp., while also predicting their drug-likeness and toxicity profiles.

Method: The anticandidal activity of D. stramonium leaf extracts was assessed using the Agar well-diffusion method and minimum inhibitory concentration (MIC) was determined by the broth dilution method. The most active extract was selected for column chromatography. Different fractions were collected and screened against pathogenic Candida spp. The most active fraction was subjected to Gas chromatography-Mass spectrometry (GC-MS), Fourier Transform-Infrared Spectroscopy (FT-IR), and Nuclear Magnetic Resonance (NMR) analysis. Additionally, computational tools such as molecular docking and ADMET prediction provided further insights into the molecular interactions between the target enzymes.

Results: In vitro anticandidal activity demonstrated that the ethyl acetate extract exhibited significant activity against human pathogenic Candida spp., with the highest zones of inhibition against Candida guilliermondii (20.33 ± 0.56 mm), Candida tropicalis (16.33 ± 0.58 mm), and Candida albicans (14.66 ± 1.05 mm), with a minimum inhibitory concentration (MIC) value of 25 μg/ml. Additionally, the most potent fraction (F8) obtained from the Column revealed significant anticandidal activity. GC-MS analysis of the F8 fraction indicated the presence of 23 compounds, with the major compounds being Phthalic acid, di (2-propylpentyl) ester (Compound 1), Pentadecane (Compound 2), Octadecane (Compound 3), Benzoic acid, 3-Amino-5-Hydroxy-, Methyl ester (Compound 4), and 1,2-Benzenedicarboxylic acid, bis (2-ethylhexyl) ester (Compound 5). This study reports all 23 compounds from D. stramonium for the first time. Furthermore, NMR studies confirmed the presence of Phthalic acid, di (2-propylpentyl) ester as the most abundant compound, designated as compound 1. Finally, docking analysis revealed that compound 1 showed good binding affinities for the tested enzymes, with the highest binding scores of -7.084 kcal/mol and -7.030 kcal/mol with Lanosterol 14-alpha demethylase (PDB ID: 5JLC, 5TZ1). The results of the in silico pharmacokinetic and drug-likeness properties indicated that compound 1 is a potential anticandidal drug candidate.

Conclusion: This study highlights that 23 compounds were reported from the leaf extract of D. stramonium for the first time. The findings suggest that compound 1 can be considered a new anticandidal drug candidate.