De novo unified robust antidiabetic pharmacophores based on biopotent hybrid material: DFT‐assisted design, optimized molecular structure, and understanding mechanism of antidiabetic bioassay

Abstract

De novo unified robust antidiabetic pharmacophores based on hybrid material were rationally designed, generated, and characterized by spectroscopic evidences and DFT (B3LYP method). These hybrid pharmacophores demonstrated robust antidiabetic activity. Semicarbazones were used for the generation of these hybrid pharmacophores. Semicarbazones of heterocyclic β‐diketones were synthesized by conventional heating as well by green approach (microwave heating). The results obtained from both the approaches have been summarized and compared. Incorporation of dimethyltin(IV) moiety into some semicarbazones of heterocyclic β‐diketones resulted in the formation of biopotent dimethyltin(IV) formulations of the type Me2SnLA where LH2 = , R = −CH3, L(1)H2, Complex 1; R = −CH2CH3, L(2)H2, Complex 2; R = −C6H5, L(3)H2, Complex 3; and R = p‐ClC6H4−, L(4)H2, Complex 4. One representative semicarbazone of heterocyclic β‐diketone (L(4)H2) and its corresponding dimethyltin(IV) complex Me2SnL(4) (Complex 4) were also studied using computational method (DFT‐B3LYP). Optimized molecular structure, bond lengths, bond angles, EHOMO, ELUMO, dipole moment, polarizability, and other global reactivity parameters were calculated. Energy gap (ΔE) of the ligand L(4)H2 and its corresponding complex has also been compared. Optimized molecular structure–antidiabetic activity relationship of two representative ligands and the corresponding complexes has also been studied. The unified hybrid pharmacophores exhibited robust antidiabetic activity.