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Some novel 30 derivatives of 1, 3 thiazine have been designed for Computational studies. This derivatives of 1,3 thiazine were subjected to molecular docking studies against E.coli Glucosamine -6 P Synthase in Complex with Fructose -6 P (PDB ID- 4 AMV) and Crystal structure of Peptide deformylase from Staphylococcus Aureus Complex with Actinonin (PDB ID- 1Q1Y) using Molegro Virtual Docker software . Then analysis (by Chem3D Pro 12.0), ADMET prediction (by Molsoft L.L.C. Software), Bioactivity Score Pridiction (by Molinspiration Software) of all 30 derivatives of thiazine were calculated. On the basis of above results 10 derivatives of thiazine were selected and synthesized by the condensation of 2-hydroxy-3- nitro5-chlorochalcones with thiourea and phenylthiourea in ethanol containing aqueous KOH solution.The characterization of all ten synthesized compound were performed and structures were confirmed by 1H NMR and Mass spectroscopy. All synthesized compound have been screened for in-vitro evaluation of antimicrobial activities by agar plate techniques. The results indicated that all the synthesized 1, 3 thiazine derivatives shows considerable antimicrobial activities.