Phytochemical, biological, DFT, and molecular docking evaluation of Euphorbia paralias.

This study aimed to bridge the knowledge gap in the unclear previous studies of the molecular processes that cause the biological activities of Euphorbia paralias by integrating phytochemical analysis with quantum chemical calculations and molecular docking investigations, providing unprecedented insights into the therapeutic potential of its chemical constituents. Seven important flavonoids were isolated and identified using spectroscopic techniques, and 34 and 13 additional compounds were identified via GC/MS analysis of the hexane and chloroform fractions, respectively. The crude methanol extract, some fractions, and isolated compounds were screened for antimicrobial activity against Gram-positive and Gram-negative bacteria. Among the tested constituents, β-sitosterol-3-O-β-D-glucoside 1, kaempferol-3-O-α-D-arabinopyranoside 4, and genistein-8-β-C-glucoside 6, as well as the chloroform and ethyl acetate fractions, demonstrated notable broad-spectrum antibacterial activity. The insecticidal activities of the butanol fraction and a combination of genistein-4'-O-β-D-glucopyranoside 2 and quercetin-3-O-β-D-glucoside 3 significantly inhibited Aphis gossypii and Amrasca biguttula, with LC values of 397.39 ppm and 332.92 ppm, respectively. DFT calculations at the B3LYP/6-31G(d) level revealed that hirsutissimiside B 7 exhibited the lowest HOMO-LUMO gap (1.643 eV), highest dipole moment (7.562 Debye), and lowest chemical hardness (0.821 eV), suggesting enhanced chemical reactivity and bioactivity. Molecular docking simulations revealed the strong binding affinities of the active compounds to key microbial and insecticidal target proteins. The high degree of concordance between computational predictions and experimental bioactivity results reinforces the therapeutic potential of these natural products. These findings highlight the synergistic value of integrating quantum chemical calculations, molecular modeling, and biological assays to advance natural product-based drug discovery and pest control strategies.