Aminoalkyl and Oxazine of 2-Naphthol Derivatives: Synthesis, In vitro Antimicrobial and In Silico Studies
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Date
2024-02
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Addis Ababa University
Abstract
Despite remarkable advancements in the past decade, infectious diseases continue to pose a
significant threat, affecting millions and burdening global public health systems and economies.
Currently, there is growing interest in 2-naphthol derivatives, particularly 1-aminoalkyl-2-
naphthol derivatives, owing to their biological activities and their potential application in
synthesizing other significant bioactive molecules. Therefore, in this study, two compounds were
synthesized from a 2-naphthol framework. The synthesized compounds were purified through
column chromatography, and their chemical structures were identified using 1H and 13C, DEPT-
90, and DEPT-135 NMR spectral data, as 1-(phenyl(ortho-tolylamino)methyl)naphthalene-2-ol
(37) and 2-benzyl-2,3-dihydro-1H-naphtho[1,2-e][1,3]oxazine (39). The potential antimicrobial
activity of the synthesized compounds was evaluated by the disk diffusion and broth dilution
method. At the same time, molecular docking and ADMET studies were conducted to investigate
their possible mechanism of action and drug-like properties.
From our findings, both synthesized compounds exhibited promising antibacterial activity against
most tested bacterial strains at 200 μg/ml, showing zones of inhibitions (ZOIs) ranging from 6.0
mm to 15.5 mm. The positive standard ciprofloxacin demonstrated ZOIs between 11.5 mm and
20.5 mm. Compound 37 exhibited greater susceptibility against E. coli with a MIC value of 25
μg/ml followed by V. cholera (MIC) at 50 μg/ml.
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In contrast, Gram-positive bacteria such as Bacillus pumilus and B. subtilis demonstrated the
lowest sensitivity to compounds (37) and (39), displaying a ZOI value of 6.0 mm at 200 μg/ml.
Both compounds 37 and 39 also displayed antifungal activity against most tested fungal species.
In molecular docking analysis, compounds (37) and (39) demonstrated significant binding energy
within the binding pocket of E. coli DNA gyrase B, yielding docking scores of -8.092 and -7.754
kcal/mol, respectively. Similarly, with C. albicans lanosterol 4α-demethylase, they displayed
docking scores of -7.792 and -8.995 kcal/mol, respectively. Following the ADMET prediction
analysis, both synthesized compounds exhibit favorable pharmacokinetics and drug-like
characteristics, making them suitable for oral administration. In addition to the in vitro bioassay
activity test, molecular docking results and ADMET predictions collectively convey the promising
antimicrobial properties of both synthesized compounds. These findings imply that conducting
further synthesis and evaluation of 2-naphthol derivatives could be beneficial in the ongoing efforts
to develop antimicrobial drugs for combating infectious diseases and microbial resistance.
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Keywords
Antimicrobial, Antibacterial, Antifungal, Mannich base, 2-naphthol, Oxazine, Aminoalkyl, in silico study, DNA gyrase B, molecular docking, ADMET