Antibacterial compounds Phenol, 2,4-bis(1,1-dimethylethyl) and Lupeol obtained from lichen-associated Streptomyces mobaraensis DRM1 and Nocardiopsis synnemataformans DRM2 respectively. The geometry, electronic properties and binding affinities of antibacterial compound Phenol, 2,4-bis(1,1-dimethylethyl) and Lupeol was determined. The in silico molecular mechanics of bacterial growth inhibition by Phenol, 2,4-bis(1,1-dimethylethyl) and Lupeol was established in Pseudomonas aeroginosa and Salmonella typhi by molecular docking, molecular simulation approach. The bacterial growth is inhibited by inactivating the vital enzyme PqsA and actin in bacterial system of Pseudomonas and Salmonella. The antibacterial compound produced by lichen associated actinobiont are adhere to Lipinski rule 5 and established criteria for drug likeness with the acceptable ADME properties and expand our understanding of their pharmacological approach. Further it also revels the adaptation and survival lichen in adverse climatic condition through the antimicrobials in lichen-associated actinobiont. Keywords: Phenol; 2,4-bis(1,1-dimethylethyl); Lupeol; Lichen; Actinobiont; NBO analysis; Molecular dynamic simulation.