The emergence of multidrug-resistant pathogens have posed a major challenge to the treatment strategies for infectious diseases. In this study, a panel of eight novel pyrano-pyrazole heterocyclic moiety were prepared by multi-component one-pot reactions. In the first step Pyrano-pyrazole moiety prepared by single pot multicomponent condensation of Ethyl 3-oxobutanoate, pyridine-4-carbohydrazide, Propanedinitrile, and substituted benzaldehydes. In the second step above synthesized pyrano- pyrazole derivative react with different substituted phenyl amino-acetyl chloride derivative to give final compound. All the compounds were obtained in reasonable yields bearing their characteristic structure as inferred from the spectral analysis. All the synthesized compounds were screened for antimicrobial activity. Product B-1, B-5 and B-8 is found to have remarkable antibacterial activity. Products B-4 and B-7 are moderately active and compound B-5 and B-6 are found to have remarkable Antifungal activity.