Synthesis, Antibacterial, Antioxidant, and Molecular Docking of Tetrahydro-??-Carboline Derivatives

Abstract

1,2,3,4-Tetrahydro-β-carbolines (THβCs) are a large group of natural and synthetic indole alkaloids that possess a common tricyclic pyrido[3,4-b] indole scaffold with wide spectrum of biological activities including antibacterial, antimalarial, antifungal, antioxidant, anticancer, anti-inflammatory and anti-leishmanial activities. In this study, four tetrahydro-β-carboline derivatives were prepared from tryptophan and aromatic or aliphatic aldehydes using Pictet Spengler reaction catalyzed by AcOH and TFA. Structure of these compounds were determined using spectroscopic methods UV-Vis and NMR ( 1H-NMR, 13C-NMR, and DEPT-135-NMR). The antibacterial activity of the synthesized compounds was screened against two Gram-positive bacterias (Staphylococcus pyogenes and Staphylococcus aureus) and two Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa) using Agar disc diffusion. Results showed that all the studied compounds displayed good antibacterial activity compared to ciprofloxacin which was used as a positive control. The best activity was displayed by compound 142c against P. aeruginosa, E. coli, and S. aureus with mean inhibition zone of 15.0 ± 1mm, 14.67 ± 1.5 mm, and 13.3 ± 1.5mm mm at 1.0 mg/mL, respectively whereas compound 142b showed higher activity against E. coli (14.3±2.1mm), P. aeruginosa (14.3±1.53mm), S. aurous (13±2.0mm), and S. pyogenes (14.3±1.53mm). DPPH radical scavenging activity displayed 90%, 92%, 91%, and 95% inhibition for compounds 140, 142a, 142b, 142c, respectively, at 100 μg/mL. In silico molecular docking analysis revealed that compound 142c exhibited better docking efficiency with DNA gyrase displaying binding affinity of -6.9kcal/mol close to ciprofloxacin (−7.2 kcal/mol). Molecular docking study was also examined using human peroxiredoxin 5 enzymes for compound 142c scoring binding affinity of -5.4 kcal/mol compared with standard antioxidant ascorbic acid (-4.9 kcal/mol). The results of in silico molecular docking study of the compounds against E. coli DNA gyrase B and human peroxiredoxin 5 enzymes were also in good agreement with in vitro antibacterial and antioxidant analysis. The in vitro antibacterial activity of compound 142b and antioxidant activity of compound 142c suggest the potential use of these compounds as potential drug lead candidates.