In Silico Evaluation of Bioactive Compounds of Artemisia pallens Targeting the Efflux Protein of Multidrug-Resistant Acinetobacter baumannii (LAC-4 Strain).
Suvaiyarasan SuvaithenamudhanSivapunniyam AnanthVanitha MariappanVictor Violet DhayabaranSubbiah ParthasarathyPitchaipillai Sankar GaneshEsaki Muthu ShankarPublished in: Molecules (Basel, Switzerland) (2022)
Acinetobacter baumannii ( A. baumannii ) is one of the major representative aetiologies of recalcitrant nosocomial infections. Genotypic and phenotypic alterations in A. baumannii have resulted in a significant surge in multidrug resistance (MDR). Of all the factors responsible for the development of antimicrobial resistance (AMR), efflux protein pumps play a paramount role. In pursuit of a safe alternative for the prevention and control of A. baumannii infections, bioactive compounds from the aerial parts of the medicinal plant Artemisia pallens were studied. GC-MS analysis of the ethanol extract of A. pallens detected five major compounds: lilac alcohol A, spathulenol, lilac alcohol C, n-hexadecanoic acid, and vulgarin. In silico examinations were performed using the Schrödinger suite. Homology modelling was performed to predict the structure of the efflux protein of A. baumannii -LAC-4 strain (MDR Ab-EP). The identified bioactive compounds were analysed for their binding efficiency with MDR Ab-EP. High binding efficiency was observed with vulgarin with a glide score of -4.775 kcal/mol and stereoisomers of lilac alcohol A (-3.706 kcal/mol) and lilac alcohol C (-3.706 kcal/mol). Our molecular dynamic simulation studies unveiled the stability of the ligand-efflux protein complex. Vulgarin and lilac alcohol A possessed strong and stable binding efficiency with MDR Ab-EP. Furthermore, validation of the absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of the ligands strongly suggested that these compounds could serve as a lead molecule in the development of an alternate drug from A. pallens .
Keyphrases
- multidrug resistant
- acinetobacter baumannii
- drug resistant
- gram negative
- klebsiella pneumoniae
- antimicrobial resistance
- binding protein
- protein protein
- alcohol consumption
- molecular docking
- pseudomonas aeruginosa
- oxidative stress
- amino acid
- emergency department
- cross sectional
- cancer therapy
- small molecule
- transcription factor
- drug delivery
- escherichia coli
- cystic fibrosis
- drug discovery