Synthesis and preliminary biological evaluation of novel steroidal compounds as antibacterial agents

Antimicrobial resistance is currently one of the most serious and alarming threats to human health; therefore, the identification of novel antimicrobial agents is a compelling need. Recently, we identified the heterocyclic steroid PYED-1 as a novel promising antibacterial and antibiofilm agent. In an effort to broaden the repertoire of active compounds and elucidate the structural features responsible for their antibacterial activity, two novel derivatives of PYED-1 have been conceived herein. The target compounds have been readily obtained in few steps and with very good yields. The antibacterial activity has been evaluated against S. aureus and A. baumannii strains, as examples of Gram-positive and -negative bacteria, by the broth microdilution method, while hemolysis assay has been used for the assessment of cytotoxicity. One of the two derivatives was able to inhibit the growth of S. aureus strains with lower MIC values (8 µg/mL) compared with those of PYED-1 (16 µg/mL) without showing hemolytic effect suggesting therefore a favorable safety profile. Overall, this study provides further indications on the functional groups required for the antibacterial activity of these novel steroidal derivatives.