TY - JOUR
T1 - Synthesis, antimicrobial activity, and molecular docking study of fluorine-substituted indole-based imidazolines
AU - Mendoza-Figueroa, Humberto L.
AU - Serrano-Alva, Maria Trinidad
AU - Aparicio-Ozores, Gerardo
AU - Martínez-Gudiño, Gelacio
AU - Suárez-Castillo, Oscar R.
AU - Pérez-Rojas, Nadia A.
AU - Morales-Ríos, Martha S.
N1 - Publisher Copyright:
© 2018, Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2018/6/1
Y1 - 2018/6/1
N2 - A series of 2- or 3-(4,5-dihydro-1H-imidazol-2-yl)-1H-indole derivatives were synthesized, characterized, and evaluated for their in vitro antibacterial and antifungal activities. Additionally, the synthesized compounds were docked into the II DNA gyrase B active site, and their predicted binding modes were inspected. Inhibitory activity were tested against two species of Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa), two species of Gram-positive bacteria (Staphylococcus aureus, Listeria monocytogenes) and two fungi (Candida albicans, Aspergillus niger) using the broth microdilution method. The fluorine-substituted 2-(2-imidazolyl)indole 2b was found to be the most potent antibacterial compound against E. coli and S. aureus strains (MIC value 80 μg/mL). Compounds showed better activity against Gram-positive bacteria compared to Gram-negative bacteria. The docking results predicted that the imidazoline-indole hybrid moiety bind to the active site protein ATP-binding pocket from E. coli and S. aureus with good interaction energy scores. The significant loss of antibacterial activity for some imidazoline-indole analogs could be attributed to several nonoptimal enzyme interactions, including poor hydrogen bonds provided by Asp73 (E. coli gyrase numbering) or Asp81 (S. aureus gyrase numbering) and an associated water molecule.
AB - A series of 2- or 3-(4,5-dihydro-1H-imidazol-2-yl)-1H-indole derivatives were synthesized, characterized, and evaluated for their in vitro antibacterial and antifungal activities. Additionally, the synthesized compounds were docked into the II DNA gyrase B active site, and their predicted binding modes were inspected. Inhibitory activity were tested against two species of Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa), two species of Gram-positive bacteria (Staphylococcus aureus, Listeria monocytogenes) and two fungi (Candida albicans, Aspergillus niger) using the broth microdilution method. The fluorine-substituted 2-(2-imidazolyl)indole 2b was found to be the most potent antibacterial compound against E. coli and S. aureus strains (MIC value 80 μg/mL). Compounds showed better activity against Gram-positive bacteria compared to Gram-negative bacteria. The docking results predicted that the imidazoline-indole hybrid moiety bind to the active site protein ATP-binding pocket from E. coli and S. aureus with good interaction energy scores. The significant loss of antibacterial activity for some imidazoline-indole analogs could be attributed to several nonoptimal enzyme interactions, including poor hydrogen bonds provided by Asp73 (E. coli gyrase numbering) or Asp81 (S. aureus gyrase numbering) and an associated water molecule.
KW - Antibacterial activity
KW - Docking studies
KW - Gyrase B
KW - Imidazole
KW - Indole
KW - Tautomers
UR - http://www.scopus.com/inward/record.url?scp=85045025489&partnerID=8YFLogxK
U2 - 10.1007/s00044-018-2177-x
DO - 10.1007/s00044-018-2177-x
M3 - Artículo
AN - SCOPUS:85045025489
SN - 1054-2523
VL - 27
SP - 1624
EP - 1633
JO - Medicinal Chemistry Research
JF - Medicinal Chemistry Research
IS - 6
ER -