Abstract: In the present study, researchers designed a Pharmacophore Model chalconesemicarbazone which is having hydrogen acceptor site, hydrogen donor site, lipophilic site, etc., using Ligandscout-2.02 software. A series of chalcone semicarbazones was synthesized and evaluated for their anti-fungal activity by Paper Disk Diffusion Method. Based on the results of an anti-fungal study, compound CS-10 was the most active compound. It was observed that methoxy substitution in aldehydic moiety and hydroxyl substitution in the acetophenic moiety significantly increased anti-microbial spectrum against fungi.