Synthesis, Characterization, Molecular Modeling Studies and Bioactivity of a Novel Bicyclic Compound of δ-lactam with Oxazepine Ring Containing Sulphur Substitute using an Economic Method

Penicillin resistance is a commonly present and controversial matter due to the misuse by people for various reasons. However, few studies have examined the bioactivity of 5- and 6- membered rings. In this study, we aimed to synthesize a new compound containing a 5-membered ring following a short and low-cost method and combined it with oxazepine ring via Schiff bases to produce a bicyclic molecule (Lactozepine). In vitro examinations were conducted to assess the bioactivity of the prepared compound, including anti-bacterial, anti-fungal and antioxidant activities, which showed a wide zone of inhibition of lactozepine against Streptococcus pneumoniae but no inhibition was shown against Klebsiella pneumoniae and Staphylococcus aureus except at a high concentration similar to the result of the anti-fungal assessment. Furthermore, lactozepine showed significant antioxidant activity against free radical formation. The molecular modeling and docking assessment showed the ability of lactozepine to bind to bacterial proteins and inhibit their growth with the lowest free energy for the greatest and strongest binding affinity with the PDB crystal structures 1VQQ, 2WAE, 1PYY and 1IYS ranging from −6.5 and −7.9 kcal/mol. Moreover, the molecular dynamics (MD) simulation showed that RMSF for the assessed protein’s amino acids remained consistent and tightly bound to lactozepine in the dynamic state. The novel compound lactozepine, with [Formula: see text]-lactam rings attached to oxazepine showed bioactivity promising for in vivo studies in the future.