Biological Activity and Molecular Docking Study of Some Bicyclic Structures: Antidiabetic and Anticholinergic Potentials

Bicyclic structures were synthesized by LACASA-DA cycloaddition reaction using (S)-BINOL as a chiral inductor. The N-2 pyridazine position was protected; the hydroxyl group was carbonylated to form the new bicyclic structure. The protective group was removed, the double bond dehydroxylated leading to the target compound. Removing of the protective group was performed using newly found ecofriendly catalyst for N-Boc deprotection. The obtained features from the model against AChE enzyme suggest that a lower the size of the ring, number of -NH-NH- groups, number of secondary aromatic amines, number of aromatic ketone groups may contribute to the inhibitory activity. The features obtained from the model against BChE enzyme suggest that the sum of topological distances between two nitrogen atoms, number of secondary aromatic amides, may be more favorable for inhibition. The features obtained from selectivity-based model suggest that the number of aromatic ethers, unsaturation content related to their molecular size and molecular shape may be more specific for the inhibition of the AChE enzyme in comparison to the BChE enzyme. Similarly, these aromatic structures inhibited the alpha-glucosidase enzyme at the micromolar level due to its structural feature. Inhibition values were found to be statistically significant, especially for cholinesterase enzymes. Molecular docking method was used to compare the biological activities of molecules against enzymes. The enzymes used in this study are alpha-glycosidase, butyrylcholinesterase, acetylcholinesterase, respectively. ADME/T analysis was performed to use some bicyclic molecules as drugs in the future.

Automated summary

Bicyclic structures were synthesized using (S)-BINOL as a chiral inductor via LACASA-DA cycloaddition reaction. The study identified different structural features that affect the inhibition of AChE and BChE enzymes, as well as the inhibitory activity of some bicyclic structures against the alpha-glucosidase enzyme.