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The growing level of antimicrobial resistance has become a severe health problem worldwide so there is a need to design new heterocyclic drug candidates. Therefore, it is now the highest priority for researchers to discover new antimicrobial hybrid molecules having a combination of two heterocyclic rings having different modes of action to solve this serious problem. We have presented an In-silico based design of some novel thiazole incorporating pyrimidine derivatives as potential antimicrobial scaffolds and studying their synergistic effect in this book. The valuable information provided in this book may be found useful for drug design and the development of new bioactive heterocyclic compounds having better therapeutic efficacy and safety. It is our sincere effort to discuss our research findings on combination of two different heterocyclic nucleus thiazole and pyrimidine for their antimicrobial activity having the ability to overcome resistance develop by microbes.