METHODS: The antibacterial activity of leaf extracts of M. cajuputi was assessed using the broth microdilution assay. Scanning electron microscopy (SEM) was used to investigate the effects of MAE on the morphology of bacterial cells. Meanwhile, the chemical composition of the MAE was analyzed using Fourier transform infrared (FTIR) spectroscopy and gas chromatography-mass spectrometry (GC-MS). AutoDock Vina was used for molecular docking analysis to unveil the interactions between the ligands and the active sites of the target bacterial proteins.
RESULTS: The crude extracts were obtained through cold maceration. The methanolic extract demonstrated the most significant antibacterial activity, with minimum inhibitory concentration (MIC) values spanning 0.25 mg/mL to 2 mg/mL. After 12 h of treatment with 1 × MIC of the methanolic extract, the bacteria showed discernible morphological alterations, including disrupted cell wall and membrane integrity. Thirty compounds were identified in the MAE and subsequently subjected to molecular docking studies against target bacterial proteins. Amongst the compounds, methylanthracene, cycloisolongifolene, diphenyl imidazole, benzil monohydrazone, and trimethoxybenzoic acid showed pronounced binding affinities towards Klebsiella pneumoniae membrane protein (PDB ID: 5O79), peptide binding protein (PDB ID: 7RJJ), Streptococcus agalactiae cell wall surface anchor (PDB ID: 2XTL), pilin (PDB ID: 3PHS), Staphylococcus aureus transglycosylase (PDB ID: 3VMQ), and penicillin-binding proteins (PDB ID: 3VSK). The binding energy scores for these interactions varied between - 6.0 kcal/mol and - 7.5 kcal/mol. Molecular dynamics simulations validated the stability of these interactions, reinforcing the in vitro findings of cell wall and membrane disruption.
CONCLUSION: The findings of this study indicated that the methanolic extract of M. cajuputi leaves displayed potent antibacterial activity against Klebsiella pneumoniae, S. agalactiae, and S. aureus. The molecular docking analysis reveals significant binding interactions between the identified compounds and the target bacterial proteins, highlighting the potential of M. cajuputi as a novel source of anti-infectives targeting bacterial infections.
OBJECTIVES: This study aimed to examine two key drug repurposing methodologies in general diseases and specifically in AD, which are artificial intelligent (AI) approach and molecular docking approach. In addition, the hybrid approach that integrates AI with molecular docking techniques will be explored too.
METHODOLOGY: This study systematically compiled a comprehensive collection of relevant academic articles, scientific papers, and research studies which were published up until November 2024 (as of the writing of this review paper). The final selection of papers was filtered to include studies related to Alzheimer's disease and general diseases, and then categorized into three groups: AI articles, molecular docking articles, and hybrid articles.
RESULTS: As a result, 331 papers were identified that employed AI for drug repurposing in general diseases, and 58 papers focused specifically in AD. For molecular docking in drug repurposing, 588 papers addressed general diseases, while 46 papers were dedicated to AD. The hybrid approach combining AI and molecular docking in drug repurposing has 52 papers for general diseases and 9 for AD. A comparative review was done across the methods, results, strengths, and limitations in those studies. Challenges of drug repurposing in AD are explored and future prospects are proposed.
DISCUSSION AND CONCLUSION: Drug repurposing emerges as a compelling and effective strategy within AD research. Both AI and molecular docking methods exhibit significant potential in this domain. AI algorithms yield more precise predictions, thus facilitating the exploration of new therapeutic avenues for existing drugs. Similarly, molecular docking techniques revolutionize drug-target interaction modelling, employing refined algorithms to screen extensive drug databases against specific target proteins. This review offers valuable insights for guiding the utilization of AI, molecular docking, or their hybrid in AD drug repurposing endeavors. The hope is to speed up the timeline of drug discovery which could improve the therapeutic approach to AD.
METHODS: Docking between ligand and FOXO1 receptor was carried out with Autodock4.2. For molecular dynamics simulations, the force fields of DNA.OL15, protein.ff14SB, gaff2, and tip3p were used.
METHODS: Molecular docking studies were performed to predict the binding affinity of Cinnamomum zeylanicum compounds to MMP-8 and MMP-9. Diabetic wound healing was evaluated using in vivo models where wounds were induced and treated with Cinnamomum zeylanicum extract. Various parameters were measured, including wound contraction, hydroxyproline content, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and malondialdehyde (MDA) levels. Biochemical analyses included glucose levels, fasting blood glucose (FBG), oral glucose tolerance test (OGTT), and histomorphological examination of skin tissues.
RESULTS: Molecular docking results indicated a high binding affinity of Cinnamomum zeylanicum's bioactive compounds with MMP-8 and MMP-9, suggesting potential inhibition. Experimental validation showed significant improvement in wound contraction and increased hydroxyproline content, indicating enhanced collagen synthesis. Antioxidant enzyme activities (SOD, GPx, CAT) were significantly elevated, while MDA levels were reduced, reflecting decreased oxidative stress. Biochemical analysis demonstrated improved glucose homeostasis with reduced FBG and enhanced OGTT responses. Histomorphological studies revealed improved tissue architecture and re-epithelialization in treated wounds.
CONCLUSION: Cinnamomum zeylanicum exhibits promising potential in diabetic wound healing by modulating MMP-8 and MMP-9 activities, enhancing antioxidant defenses, and improving glucose regulation. These findings support its therapeutic application for diabetic wounds, providing a foundation for further clinical investigations.