Novel piperazine based compounds as potential inhibitors for SARS-CoV-2 Protease Enzyme: Synthesis and molecular docking study

Abstract

Structurally diverse piperazine-based compounds hybrid with thiadiazole, isatin or with sulfur/nitrogen, functionalities were synthesized. The structures of the new compounds were established based on their spectral data and elemental analysis. The physicochemical, bioactivity scores and pharmacokinetic behavior of all the prepared ligands were evaluated using in silico computational tools. The new piperazine ligands have been screened for their inhibition activity against SARS-CoV-2 protease enzyme using molecular docking analysis. The docking studies showed that all the ligands have been docked with negative dock energy onto the target protease protein. Moreover, Molecular interaction studies revealed that SARS-CoV-2 protease enzyme had strong hydrogen bonding interactions with piperazine ligands. The present in silico study thus, provided some guidance to facilitate drug design targeting the SARS-CoV-2 main protease.

Methodology-Centered Review of Molecular Modeling, Simulation, and Prediction of SARS-CoV-2

“…Among them, the best one was bisoctrizole . Additionally, some diaminobenzophenone derivatives, prototypical-ketoamide inhibitors, HIV protease inhibitors, leucoefdin, nutraceuticals, and others were also studied. ,,,,− Notably, Mohammad et al optimized some complexes of Mpro with ligands in the protein data bank (PDB) and rescored them by AutoDock Vina, with the best PDB structure being 6M2N.…”

Synthesis and Antimicrobial Activity Screening of Piperazines Bearing N,N′-Bis(1,3,4-thiadiazole) Moiety as Probable Enoyl-ACP Reductase Inhibitors

“…The synthesized 5,5′-(piperazin-1,4-diyl)bis(1,3,4-thiadiazole-2-thiol) 1 [54] was selected as a precursor to give 1,4-bis(5-hydrazinyl-1,3,4-thiadiazol-2-yl)piperazine 2 and 1,4-bis(5-chloro-1,3,4-thiadiazol-2-yl)piperazine 3 by its reaction with 98% hydrazine hydrate [55] and thionyl chloride in benzene [56], respectively; see Scheme 1. Owing to the above facts and in continuation of the research on enoyl ACP reductase inhibitors, an attempt was made in the present research to design and develop new anti-E. coli agents possessing enoyl ACP reductase inhibition.…”

“…The synthesized 5,5 -(piperazin-1,4-diyl)bis(1,3,4-thiadiazole-2-thiol) 1 [54] was selected as a precursor to give 1,4-bis(5-hydrazinyl-1,3,4-thiadiazol-2-yl)piperazine 2 and 1,4-bis(5-chloro-1,3,4-thiadiazol-2-yl)piperazine 3 by its reaction with 98% hydrazine hydrate [55] and thionyl chloride in benzene [56], respectively; see Scheme 1.…”

Mesomorphic, Computational Investigations and Dyeing Applications of Laterally Substituted Dyes

“…Chemical descriptor parameters [35][36][37][38] of the dispersed azo dyes 1-10 were computed using B3LYP/6-311G level to examine their dyeing performance, Table 5. The energy of the highest occupied molecular orbitals E HOMO as well as the energy of the lowest unoccupied E LUMO of any chemical species are related to their ionization potential IP and electron affinity EA values [35][36][37][38][39]. Moreover, the global parameters including energy gap (∆E) [40], electrophilicity index (ω), absolute electronegativity (χ), absolute hardness (η), absolute softness (σ), and chemical potential (µ) were calculated [41].…”