Integrated computational and experimental studies on benzothiazine–chalcone hybrids: Crystal Structures, in silico modeling, and in vitro evaluation of α-glucosidase inhibition and antioxidant activity

The pharmacophore fusion approach is a well-established strategy in drug discovery for designing new pharmacophores from the existing pharmacophores with potential biological applications. The 1,2-benzothiazine based ketone is condensed with halogenated aldehydes to isolate 1,2-benzothiazine hybrid chalcones. These compounds were further characterized by FT-IR, NMR and molecular structures were determined by X-ray crystallography. The presence of C=O and C=C groups at 1616-1602 cm -1 and 1600-1577 cm -1 indicates the formation of chalcone derivatives. The molecular structures based simulation studies were carried out to find out the HOMO-LUMO gap, MEP, NPA, NBO, global reactive descriptors, dipole moments and polarizabilities. Theoretical studies indicated that oxygen atoms are electron rich sites and represented in red color and nitrogen atoms are electron deficit sites and are in blue color. The high electron density resides on σ→σ* followed by π→π*. The 3-fluoro substituted benzothiazine based chalcone (3) has more electrostatic character of 6.674 eV making it a more suitable candidate for biological interactions and is more stable and less polarized. The theoretical NMR and FT-IR studies are in good agreement with the obtained results. In order to examine the antidiabetic potential of these compounds, both wet and dry lab methods were used. The in vitro studies assess their inhibitory potential against α-glucosidase linked to diabetes as well as against DPPH. The inhibitory potential revealed that compound 3 has higher inhibition potential (IC 50 = 476.70 µg/mL) as compared to other molecules. Similarly, compound 3 depicted maximum free radical scavenging activity (IC 50 = 217.30 µg/mL). Molecular docking studies also show close agreement between in vitro and in silico behavior.