*Corresponding Author: gyanranjan.mahalik@cutm.ac.in 249 DOI: https://doi.org/10.52756/ijerr.2024.v42.022 Int. J. Exp. Res. Rev., Vol. 42: 249-261 (2024) Antibacterial Activity, Toxicity and Drug-Likeness Profiles of Woodfordia fruticosa-Derived Metabolites Using Computational-Aided Drug Design Platform Dileswar Sahu 1 , Ram Babu 2 , Srinivas Acharya 3 , Shasank S. Swain 4 and Gyanranjan Mahalik 1* 1 Department of Botany, School of Applied Sciences, Centurion University of Technology and Management, Bhubaneswar-751050, India; 2 Department of Botany, Kirori Mal College, University of Delhi, Delhi-110007, India; 3 Department of Environmental Science, Government Autonomous College Phulbani, Kandhamal-762001, Odisha, India; 4 Research and Development Division, Salixiras Research Private Limited, Bhubaneswar-751012, Odisha, India E-mail/Orcid Id: DS, dileswarsahu1987@gmail.com, https://orcid.org/0009-0008-2582-8767; RB, rbsjnu@gmail.com, https://orcid.org/0009-0003-8997-3318; SA, srinivasacharya06@gmail.com, https://orcid.org/0000-0001-6095-4840; SSS, salixiras.bbsr@gmail.com, https://orcid.org/0000-0001-5089-8304; GM, gyanranjan.mahalik@cutm.ac.in, https://orcid.org/0000-0003-4953-9982 Introduction Antibiotic resistance in the 21 st century has emerged as a critical global health challenge, posing a threat to the effectiveness of commonly used antibiotics and their ability to combat bacterial infections (GBD 2019; Ranjbar and Alam, 2022; WHO, 2023a). The misuse and overuse of antibiotics in humans, animals and agriculture have accelerated the development of resistant strains, creating a scenario where once-treatable infections become more difficult or even impossible to manage. The consequences of antibiotic resistance include increased morbidity, mortality, prolonged illness and higher healthcare costs (Aslam et al., 2018; GBD 2019; Ranjbar and Alam, 2022; WHO, 2023a). Therefore, the emergence of antibiotic-resistant strains in these diseases underscores the urgent need for global efforts in surveillance, prudent antibiotic use and the development of novel therapeutic strategies to combat this growing public health crisis (Aslam et al., 2018; GBD 2019; Ranjbar and Alam, 2022; WHO, 2023a). Infections Article History: Received: 06 th May, 2024 Accepted: 11 th Aug., 2024 Published: 30 th Aug., 2024 Abstract: This study presents a comprehensive investigation into the phytoconstituents reported from Woodfordia fruticosa (L.) Kurz leaf and flower extracts using gas chromatography-mass spectrometry (GC-MS) analysis, along with some existing phytochemicals, to explore their potential antibacterial properties through molecular docking studies. Followed by bio-assay-guided leave and flower extraction with two solvent systems, i.e., methanol (polar) and petroleum ether (non-polar), was used and further subjected to GC-MS to identify and quantify various secondary metabolites. Based on spectral intensity and volume area, a total of 28 compounds (P1 to P28) have been selected from GC-MS analyses, and an additional 14 compounds (P29 to P42) from previous reports were selected for molecular docking studies against DNA gyrase subunit B (GryB) of Escherichia coli (PDB ID: 7P2M) and Staphylococcus aureus (PDB ID: 5D7R) with novobiocin as the standard. Further, docking score or binding affinity (kcal/mol.) of each ligand were investigated, where the 4,5-dihydro-4,4-undeca methylene-2-phenyl-1,3-oxazin-6-one (P20) with a docking score of -8.4 kcal/mol., from the GC-MS-derived group and the chrysophanol-8-O-β-d-glucopyranoside (P37) with a docking score of -9.7 kcal/mol., from existing phytochemical groups were reported as potential antibacterial. The predicted toxicity and drug-ability profiles also suggested that GC-MS-derived candidates displayed comparatively higher non-toxic profiles but lower drug-likeness profiles than existing groups. This integrative approach explores the phytochemical profiles of W. fruticosa responsible for antibacterial activity of the crude extracts and providing insights into in selection of lead antibacterial agent through cost-effective computer-aided drug design platform to accelerate antibacterial drug discovery with higher chance of experimental success. Keywords: Woodfordia fruticosa (L.) Kurz, Antibacterial activity, Gas Chromatography-Mass Spectrometry, Molecular docking, Toxicity prediction How to cite this Article: Dileswar Sahu, Ram Babu, Srinivas Acharya Shasank S. Swain and Gyanranjan Mahalik (2024). Antibacterial Activity, Toxicity and Drug-Likeness Profiles of Woodfordia fruticosa-Derived Metabolites Using Computational-Aided Drug Design Platform. International Journal of Experimental Research and Review, 42, 249-261. DOI: https://doi.org/10.52756/ijerr.2024.v42.022