identification of 1chloro2formyl indenes and tetralenes as novel antistaphylococcal agents exhibiting sortase a inhibition tetralene and indene compounds have shown inhibitory activity against human pathogen mycobacterium tuberculosis their potential use as antistaphylococcal agent against drugresistant staphylococcus aureus has not been explored so far we determined in vitro antistaphylococcal activity and mechanism of action of these compounds as sortase a inhibitors through in silico analysis followed by biological assays tetralene and indene series were tested against s aureus strains mtcc96 mrsa and va30 three compounds showed significant reduction in mic in both wildtype and drugresistant s aureus strains in silico absorption distribution metabolism excretion and toxicity analysis of identified leads and cytotoxicity testing with colorimetric method using vero and wrl68 cell lines showed no significant cytotoxic effects molecular docking of these molecules with sortase a pdb 2kid showed hbond interaction with functional site residue arg197 of sortase a sortase a inhibition assay was developed by expressing srtan from s aureus strain mtcc96 tetralene and indene compounds were found to have sortase a inhibitory potential s aureus strain mtcc96 treated with these compounds showed surfacesorting inhibition of fibronectinbinding protein and reduction in adherence to host extracellular matrix protein fibronectin 1chloro 2formyl 6methoxy 1tetralene tet5 15dichloro 2formyl 1indene tet20 and 1chloro 2formyl 56methylenedioxy and 1indene tet21 exhibited antistaphylococcal activity along with sortase a inhibition the results also indicate the possible role of these leads in other reactions essential for cell viability