الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
from the generated pharmacophore model, it was concluded that the structural features essential for antibacterial activity against gram negative bacteria are the presence of one H-bond acceptor (F1) and three hydrophobic (F2, F3 and F4) moieties. Also , it was found that the two hydrophobic (F2 and F3) moieties should reside at certain distance about 5.14 and 4.27 Aᵒ, respectively, from the hydrophobic region F4. In addition, the three hydrophobic regions (F2, F3 and F4) should be separated from the H-bond acceptor moiety by a distance of 5.44, 5.18 and 2.90 Aᵒ, respectively.
Since the pharmacophore model obtained from the most active compounds was validated using the non-classical DHFR inhibitors PTX and TMQ, it appeared logic to further investigate these active compounds as DHFR inhibitors. These compounds were docked into the active site of EcDHFR in order to identify the ligand-protein binding patterns.
Molecular docking studies revealed that all docked compounds (4a, 4b, 5a, 5b, 8, 9, 14a, 16b, 17a, 17b, 17c, 22 and 37b) showed good fitting into EcDHFR active sites. They displayed hydrogen bonding interactions with the residue(s) Arg52 and/or Arg57 and hydrophobic interactions with the same residues involved in binding interactions in the EcDHFR-MTX crystal structure. They also assumed a relatively similar binding pattern as that found in the crystal structure MTX with EcDHFR. This might be attributed to their activity as antimicrobial DHFR inhibitors.