Synthesis, characterization, antimicrobial activity and molecular docking studies of combined pyrazol-barbituric acid pharmacophores

Purpose: To synthesize, and determine the antibacterial activity and binding mode of new pyrazolbarbituric acid derivatives in a search for new antimicrobial agents.Methods: One-pot multi-component reaction of aldehyde derivatives, barbituric acid and 3-methyl-1- phenyl-1H-pyrazol-5(4H)-one in the presence of NHEt2 to afford Michael adduct was carried out. The reaction was carried out in water and afforded new heterocycles in a one-step fashion, with expedient work-up and high yield without extraction and purification steps. The synthesized compounds were evaluated for antimicrobial activity using agar disc diffusion. Molecular docking approach via MOE-Dock program was applied to predict the binding interactions of some of the new pyrazol-barbituric acid derivatives against six different target proteins downloaded from Protein Data Bank.Results: A series of pyrazole-barbituric acid derivatives were successfully synthesized and characterized. The synthesized compounds showed moderate to very good antibacterial activity against S. aureus ATCC 29213 and E. faecalis ATCC29212, as well as also antifungal activity against Candida albicans ATCC 10400Conclusion: A series of pyrazole-barbituric acid derivatives has been synthesized and some of them display antimicrobial activities.Keywords: Pyrazole, Barbituric acid, Pyrazole-barbituric acid derivatives, Antimicrobial activity, Molecular dockin

Synthesis, and characterization of a new series of sulfite and sulfate derivatives of d-Mannitol

In this work, synthesis and characterization of a series of d-Mannitol derivatives with sulfite 2a–d and sulfate 3a–d moieties have been investigated. The method entails a two-step synthesis. The first step involves the Sharpless-type reaction of DIOL 1a–d with SOCl2 in CH2Cl2 in the presence of Et3N to afford the intermediate sulfite derivatives 2a–d in good yield. The second step includes the oxidation reaction of the resulting intermediate in the presence of NaIO4 in a mixture of CCl4/CH3CN/H2O (3/3/2 ratio) in the presence of catalytic amount of RuCl3·H2O to afford the desired sulfate moiety 3a–d in a moderate to high yield (66–96%). The structures of all newly synthesized compounds have been elucidated by 1H, 13C NMR, GCMS, and IR spectrometry