Exploring novel bromo heterocyclic scaffold and theoretical explanation of their biological actions.

• Reactivity of (E)−1-(2‑bromo-4-methylphenyl)−3-(4-bromophenyl)prop‑2-en-1-one with nitrogen nucleophile's and active methylene. • Antimicrobial and antioxidant activities of bromo heterocyclic derivatives'. • Docking simulation of synthesized compounds with different proteins. • Optimization of synthesized compounds utilized DFT/B3LYP-6311(G) basis set and determination of their physical descriptors. In this elucidation, we synthesized different heterocyclic compounds through (E)-1-(2‑bromo-4-methylphenyl)-3-(4-bromophenyl)prop‑2-en-1-one(3) which is synthesized from the aldol condensation between 4-bromobenzaldehyde and 1-(2‑bromo-4-methylphenyl)ethan-1-one in the basic condition in excellent yield. Furthermore, the chalcone 3 showed also varied activity with nitrogen nucleophiles and active methylene and displayed different heterocyclic rings which were confirmed through different spectral analyses such as FT-IR, 1HNMR, 13CNMR, and mass spectrum. Moreover, the synthesized heterocyclic exhibited antimicrobial properties against various microbial strains (Gram-positive, Gram-negative, and fungal strains) through the well diffusion methodology and comparable with Ampicillin and Mycostatin drugs. Furthermore, the synthesized compounds demonstrated various radical scavenger properties and antioxidant activities. These biological analyses demonstrated various binding energies and interactions with proteins and were validated through molecular docking studies using distinct protein pockets interaction. Additionally, the Frontier Molecular Orbitals (FMO), which are physical descriptors of optimal structures that are connected with biological evaluations and demonstrate the activities of these compounds due to presence of two bromine atom which effect on electron deficiency and increase its action which examined via the DFT/B3LYP/6-311G basis set. [Display omitted] [ABSTRACT FROM AUTHOR]