The irrational use of antibiotics has favored the emergence of resistant bacteria, posing a serious threat to global health. To counteract antibiotic resistance, this research seeks to identify novel antimicrobials derived from essential oils that operate through several mechanisms. It aims to evaluate the quality and composition of essential oils from Origanum compactum and Origanum elongatum; test their antimicrobial activity against various strains; explore their synergies with commercial antibiotics; predict the efficacy, toxicity, and stability of compounds; and understand their molecular interactions through docking and dynamic simulations. The essential oils were extracted via hydrodistillation from the flowering tops of oregano in the Middle Atlas Mountains in Morocco. Gas chromatography combined with mass spectrometry (GC-MS) was used to examine their composition. Nine common antibiotics were chosen and tested alone or in combination with essential oils to discover synergistic effects against clinically important and resistant bacterial strains. A comprehensive in silico study was conducted, involving molecular docking and molecular dynamics simulations (MD). O. elongatum oil includes borneol (8.58%), p-cymene (42.56%), thymol (28.43%), and carvacrol (30.89%), whereas O. compactum oil is mostly composed of γ-terpinene (22.89%), p-cymene (15.84%), thymol (10.21%), and (E)-caryophyllene (3.63%). With O. compactum proving to be the most potent, these essential oils showed antibacterial action against both Gram-positive and Gram-negative bacteria. Certain antibiotics, including ciprofloxacin, ceftriaxone, amoxicillin, and ampicillin, have been shown to elicit synergistic effects. To fight resistant bacteria, the essential oils of O. compactum and O. elongatum, particularly those high in thymol and (E)-caryophyllene, seem promising when combined with antibiotics. These synergistic effects could result from their ability to target the same bacterial proteins or facilitate access to target sites, as suggested by molecular docking simulations. Molecular dynamics simulations validated the stability of the examined protein–ligand complexes, emphasizing the propensity of substances like thymol and (E)-caryophyllene for particular target proteins, opening the door to potentially effective new therapeutic approaches against pathogens resistant to multiple drugs.

Anethum graveolens is an aromatic plant traditionally used as an antispasmodic and carminative. The objective of this study is to analyze the chemical composition of the essential oils and extracts obtained from seeds gathered in Errachidia, southern Morocco. Additionally, the antioxidant and antimicrobial properties of these oils and extracts will be evaluated. GC-MS analysis of the EO isolated by hydrodistillation revealed that its main compounds were E-anethole (38.13%), estragole (29.32%), fenchone (17.21%), and α-pinene (7.37%). The phenolic components were extracted using the methods of decoction and Soxhlet. The assay of the phenolic compounds showed that A. graveolens seeds contained considerable amounts of polyphenols, flavonoids, and condensed tannins, with variable levels depending on the extract analyzed. HPLC/UV-ESI-MS analyses performed on the decoction revealed a structural diversity of the molecules present in this extract, the most important of which were umbelliferone (12.35%), 3-hydroxyflavone (11.23%), rosmanol (8.95%), biotin (8.36%), emmotin H (4.91%), and coumarin (4.21%). The antioxidant activity, as determined by three techniques (DPPH•, FRAP, and CAT), demonstrated that the essential oils (EOs) and extracts had a potent capacity to counteract detrimental free radicals, control the generation of reactive oxygen species, and mitigate oxidative damages. The antimicrobial activity of the Eos and extracts was carried out in a liquid medium against five strains (E. cloacae, K. pneumoniae, E. coli, S. aureus, and S. epidermidis) and four candidiasis (C. albicans, C. dubliniensis, C. tropicalis, and C. parapsilosis) and Aspergillus niger. The results showed the effectiveness of the EOs compared to the aqueous, ethanolic, and decoction extracts against most of the microorganisms tested. In addition, the ethanolic extract showed antifungal activity that was distinguished from that of the other extracts. The antimicrobial efficacy of the essential oils under study can primarily be attributed to the synergistic interactions among its three principal constituents (E-anethole, estragole, and fenchone). Furthermore, molecular docking and molecular dynamics simulation results reveal significant interactions and stability between the selected bioactive compounds and different target proteins involved in antimicrobial and antioxidant activities. Compounds like 3-hydroxyflavone, emmotin H, trans-caftaric acid, methyl rosmarinate, 1-caffeoyl-beta-D-glucose, and kaempferol exhibited better binding energies with the explored proteins, indicating their potential as antimicrobial and antioxidant agents. Finally, our findings emphasize the significance of A. graveolens seeds as a promising reservoir of advantageous health compounds that can serve as organic substitutes for the presently employed synthetic preservatives.

The severe acute respiratory syndrome coronavirus 2, also known as SARS-CoV-2, is the causative agent of the COVID-19 global pandemic. SARS-CoV-2 has a highly conserved non-structural protein 12 (NSP-12) involved in RNA-dependent RNA polymerase (RdRp) activity. For the identification of potential inhibitors for NSP-12, computational approaches such as the identification of homologous proteins that have been previously targeted by FDA-approved antivirals can be employed. Herein, homologous proteins of NSP-12 were retrieved from Protein DataBank (PDB) and the evolutionary conserved sequence and structure similarity of the active site of the RdRp domain of NSP-12 was characterized. The identified homologous structures of NSP-12 belonged to four viral families: Coronaviridae, Flaviviridae, Picornaviridae, and Caliciviridae, and shared evolutionary conserved relationships. The multiple sequences and structural alignment of homologous structures showed highly conserved amino acid residues that were located at the active site of the RdRp domain of NSP-12. The conserved active site of the RdRp domain of NSP-12 was evaluated for binding affinity with the FDA-approved antivirals, i.e., Sofosbuvir and Dasabuvir in a molecular docking study. The molecular docking of Sofosbuvir and Dasabuvir with the active site that contains conserved motifs (motif A-G) of the RdRp domain of NSP-12 revealed significant binding affinity. Furthermore, MD simulation also inferred the potency of Sofosbuvir and Dasabuvir. In conclusion, targeting the active site of the RdRp domain of NSP-12 with Dasabuvir and Sofosbuvir might reduce viral replication and pathogenicity and could be further studied for the treatment of SARS-CoV-2.

A library of thirty-one quinazoline derivatives was assessed as potential inhibitors of epidermal growth factor receptor kinase (EGFR) using 3D-QSAR methods, namely Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA). Training and test sets were generated by aligning the molecules to the lowest-energy conformer of the most active compound. The optimized models exhibited strong statistical performance, with R² values of 0.981 (CoMFA) and 0.978 (CoMSIA), and cross-validation coefficients (Q²) of 0.645 and 0.729, respectively. External validation confirmed their predictive power, yielding R² values of 0.929 and 0.909. Guided by these models, eighteen new quinazoline candidates were designed and evaluated for drug likeness and ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) properties using in silico approaches. Molecular docking and molecular dynamics simulations highlighted the binding features and stability of these derivatives, with compound Pred65 demonstrating superior affinity and stability compared to Erlotinib. Collectively, the study provides valuable insights for the optimization of quinazoline scaffolds as EGFR inhibitors, supporting the development of promising anticancer leads.