Synthesis, in vitro anti-urease, In-silico molecular docking study and ADMET predictions of piperidine and piperazine Morita-Baylis-Hillman Adducts (MBHAs)

Abstract

The current work describes an efficient synthesis of Morita-Baylis-Hillman adducts (MBHAs) derived heterocycles (4, 5, 6, 7, 10, 11, 12, 13, 16 and 17) with the Michael addition of piperidine and piperazine heterocycles. The comparative studies of mono and di-hydrogen bond acceptors heterocycles, meta and para substituted nitro-phenyl rings and the isolated single diastereomer 16 through molecular docking coupled with in vivo bioactivities displayed very important results. The biological significances were observed against urease enzyme (IC₅₀ = 3.95 ± 0.10 µM). Almost all the compounds displayed different ranges of inhibition potential whereas the di-hydrogen bond donor diastereomers 12 and 13 were found to be highly potent against the targeted enzyme while the remaining had shown comparable inhibitory activity. The diastereomers 12 and 13 were the most active having minimum inhibitory concentration (MIC) IC₅₀ = 3.95 ± 0.10 µM. All the synthesized compounds were docked and their best poses were explored for enhanced biological properties. The molecular docking studies revealed better binding interactions of the ligand with the target enzyme. Furthermore, ADMET predictions were also observed which revealed drug like properties for all the novel MBHAs based piperidine and piperazine derivatives.

Keywords: ADMET; Morita-Baylis-Hillman adduct; anti-urease; molecular docking; piperazine.