Novel Alanine-based Antimicrobial and Antioxidant Agents: Synthesis and Molecular Docking

Melford C Egbujor

doi:10.17485/ijst/2020/v013i09/146687

Abstract

Objective: To synthesize new alanine-based phenyl sulphonamide derivatives with significant antimicrobial and antioxidant activities. Methods: The reaction of alanine with benzene sulphonyl chloride afforded compound 3a. The ammonolysis of its N-acylated derivative gave the carboxamide which yielded the aryl/heteroaryl derivatives compounds 3d, 3e, and 3f via Buchwald–Hartwig nickel catalyzed amidation reaction. Structures agreed with the spectra data. Their antimicrobial activities, antioxidant activities, and molecular docking interactions were evaluated. Findings: Compounds 3f and 3a was the best antimicrobial agents with minimum inhibitory concentration (MIC) range of 0.5–1.0 µg/ml while compound 3a displayed the highest in vitro antioxidant percentage inhibition of 95.70% and the best 50% inhibitory concentration (IC50) value of 1.072 ± 0.002 µg/ml comparable to ascorbic acid of 96.38% antioxidant percentage inhibition and 0.999 ± 0.001 µg/ml IC50 value. Compounds 3c, 3a, and 3f had the highest in silico antibacterial, antifungal, and antioxidant binding energies of −10.03, −11.79, and −13.13 kcal/mol, respectively. Novelty/improvement: Alanine was found to potentiate the antimicrobial and antioxidant actions of benzenesulphonamide and carboxamide derivatives. Keywords: Alanine, Antimicrobial, Phenylsulphonamide, Molecular Docking, Antioxidant.

Highlights

The world is faced with the enormous challenge of combating microbial and oxidative stress-related diseases; these two disease conditions have brought untold misery to millions of individuals around the world [1,2,3]
Alanine is an excellent target for the design of antimicrobial drugs because of its ability to be metabolized by bacteria and alanine being an α-amino acid is utilized in protein biosynthesis and glucose– alanine cycle [7,8]
The carboxamide molecules are present in numerous drug molecules acting as a bioactive moiety [17] while the coupling partners such as aniline, pyridine, and pyrimidine exhibit numerous pharmacological activities [18,19] are used in the production of paracetamol [20], central nervous system (CNS) stimulants [21,22], and antifolates [23], respectively that amino acid-based sulphonamide and carboxamide derivatives exhibited excellent antimicrobial and antioxidant activities [24,25,26]

Summary

Introduction

The world is faced with the enormous challenge of combating microbial and oxidative stress-related diseases; these two disease conditions have brought untold misery to millions of individuals around the world [1,2,3]. Their relationship is based on the fact that oxidative stress causes a decline in immunity thereby making the body vulnerable to microbial infections [4]. The carboxamide molecules are present in numerous drug molecules acting as a bioactive moiety [17] while the coupling partners such as aniline, pyridine, and pyrimidine exhibit numerous pharmacological activities [18,19] are used in the production of paracetamol [20], CNS stimulants [21,22], and antifolates [23], respectively that amino acid-based sulphonamide and carboxamide derivatives exhibited excellent antimicrobial and antioxidant activities [24,25,26]

Methods

Results

Conclusion