Journal of Natural Products
Article
Waals interactions of the ligand with the enzyme were
considered to obtain the final output (Figure 5). The results
revealed that compound 16 (3,4-difluorophenacyl) showed
hydrogen bonding with TYR158 and GLN100 and π−π stacking
with PHE97 and PHE149. Compound 27 (2-acylnaphthalene)
bonded with the protein at TYR158 and MET98 residues via
hydrogen bonding, while displaying π−π stacking with PHE149.
Compound 36 exhibited a hydrogen bond with GLN100 and
π−π stacking with PHE97. It is interesting to note that the usnic
acid occupied the active site of the enzyme in compound 36,
while the triazole functionality was observed to fit in the same
pocket in the case of compounds 16 and 27. This study throws
emphasis on the fact that usnic acid may be a potential
antitubercular molecule with necessary structural iterations. In
addition, it can also be hypothesized that the antitubercular
property of the active compounds may be prominent via
inhibition of InhA enzyme as evident from interactions within
the active pocket residues.
In conclusion, 1,2,3-triazoles with diverse substitutions were
coupled to usnic acid and the products were tested as
antibacterial and antitubercular agents. The study throws light
on some important aspects pertaining to the presence of halogen
atoms and their number wherein two fluorine atoms is optimum
for antitubercular activity, while more or less is unfavorable. On
the other hand, the presence of more fluorine atoms is favorable
for bacterial inhibition, while only one fluorine atom caused a
decrease in the antibacterial activity. Among the tested
compounds, compound 36 was found to exert maximum
antitubercular activity but failed to show any antibacterial
activity on B. subtilis. The display of highly selective antibacterial
activity toward B. subtilis by the synthesized triazoles is
noteworthy and may be considered for further studies. In
conclusion, compound 36 displayed maximum antitubercular
activity, while compounds 18 and 29 exerted good antibacterial
activity. Compounds 16 (3,4-difluorophenacyl), 17 (perfluor-
ophenacyl), 27 (naphthalene-2-yl), and 42 [4-(2-
methoxyphenyl)piperazinyl] showed both antitubercular and
antibacterial activities. Compounds 16 and 27 look promising
for future drug discovery and development.
002946). P.K.B. is thankful to the Department of Science and
Technology, INSPIRE research fellowship, CSIR-IICT com-
munication number: IICT/Pubs./2019/168. We thank Dr. A.
Manjula (FAC division, CSIR-IICT) for proofreading and
correcting the manuscript.
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ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
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S
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Copies H and 13C NMR spectra of all the final triazole
molecules along with complete experimental procedures
X-ray crystal data and the corresponding details (CIF)
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AUTHOR INFORMATION
Corresponding Author
*Tel: +91-4027191438. Fax: +91-4027198933. E-mail:
ORCID
Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS
The authors thank SERB, Department of Science and
Technology, India, for financial assistance (EMR/2017/
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