Synthesis and characterization of novel imidazoquinoline based 2-azetidinones as potent antimicrobial and anticancer agents

AbstractA new series of N-substituted azetidinones (9a–h) synthesized by condensation of 4-arylidene hydrazino 1-isobutyl-1H-imidazo[4,5-c]quinolines (8a–h) with chloroacetyl chloride afforded 4-arylazetidin-2-ones (9a–h). The synthesized compounds were characterized by 1H NMR, 13C NMR, mass spectral and elemental analyses. All synthesized compounds were screened for their in vitro antimicrobial and anticancer activities. The hydrazone derivatives (8a–h) showed good antibacterial activity. Compounds 9a and 9b exhibited good anticancer activity. In a molecular docking study compounds 9a and 9b showed minimum binding energy and good affinity towards the active pocket. Thus, are believed to be good inhibitors of β-tubulin

1-Isobutyl-N,N-dimethyl-1H-imidazo[4,5-c]quinolin-4-amine

In the title compound, C16H20N4, the 1H-imidazo[4,5-c]quinoline ring system is approximately planar, with a maximum deviation of 0.0719 (15) Å. An intra­molecular C—H⋯N hydrogen bond contributes to the stabilization of the mol­ecule, forming an S(6) ring motif. In the crystal, the mol­ecules are stacked along the b axis through weak aromatic π–π inter­actions between benzene and imidazole and benzene and pyridine rings [centroid–centroid distances = 3.6055 (10) and 3.5342 (10) Å, respectively]

4-Hydrazinyl-1-isobutyl-1H-imidazo[4,5-c]quinoline

In the title compound, C14H17N5, the 1H-imidazo[4,5-c]quinoline ring system is essentially planar, with a maximum deviation of 0.0325 (7) Å. In the crystal, a pair of inter­molecular N—H⋯N hydrogen bonds link neighbouring mol­ecules, forming an inversion dimer and generate an R 2 2(10) ring motif. These dimers are further connected into a chain along the b axis via inter­molecular C—H⋯N hydrogen bonds, resulting in an R 2 2(14) ring motif

4-Chloro­benzaldehyde (1-isobutyl-1H-imidazo[4,5-c]quinolin-4-yl)hydrazone monohydrate

In the title compound, C21H20ClN5·H2O, the 1H-imidazo[4,5-c]quinoline ring is approximately planar, with a maximum deviation of 0.0795 (7) Å, and it forms a dihedral angle of 7.65 (3)° with the chloro­phenyl ring. In the crystal, the components are linked into chains along the a axis via inter­molecular N—H⋯O, O—H⋯N and C—H⋯O hydrogen bonds. One of the H atoms of the water mol­ecule is disordered over two positions with a site-occupancy ratio of 0.80 (4):0.20 (4)

1-Isobutyl-4-meth­oxy-1H-imidazo[4,5-c]quinoline

In the title compound, C15H17N3O, the 1H-imidazo[4,5-c]quinoline ring system is approximately planar, with a maximum deviation of 0.036 (1) Å. The C—N—C—C torsion angles formed between this ring system and the isobutyl unit are −99.77 (16) and 79.71 (17)°. In the crystal, inter­molecular C—H⋯O hydrogen bonds link the mol­ecules into chains along the c axis

(E)-4-Phenyl­butan-2-one oxime

In the title compound, C10H13NO, the C—C—C—C torsion angle formed between the benzene ring and the butan-2-one oxime unit is 73.7 (2)°, with the latter lying above the plane through the benzene ring. In the crystal, inter­molecular O—H⋯N hydrogen bonds link pairs of mol­ecules into dimers, forming R 2 2(6) ring motifs which are stacked along the a axis

2-Azido-1-(3,6-dichloro-9H-fluoren-1-yl)ethanone

In the title compound, C15H9Cl2N3O, an intra­molecular C—H⋯O inter­action generates an S(7) ring motif. The cyclo­penta-1,3-diene ring forms dihedral angles of 1.93 (6) and 2.78 (6)° with its attached benzene rings. In the crystal, mol­ecules are linked by C—H⋯N and C—H⋯O hydrogen bonds, thereby forming layers lying parallel to the ac plane. The crystal also features a π–π inter­action with a centroid–centroid distance of 3.5612 (6) Å

3-[(1-Isobutyl-1H-imidazo[4,5-c]quinolin-4-yl)amino]benzoic acid

In the title compound, C21H20N4O2, the statistically planar 1H-limidazole ring [maximum deviation = 0.003 (1) Å] makes dihedral angles of 1.33 (9) and 8.23 (7)°, respectively, with the essentially planar fused pyridine ring [maximum devation = 0.018 (1) Å] and the pendant benzene ring, which is attached to the pyridine ring by an —NH— group. An intramolecular C—H...N interaction, which generates an S(6) ring, helps to estalish the molecular conformation. In the crystal, the molecules are linked by N—H...O, C—H...O and O—H—N hydrogen bonds, which generate bifurcated R12(6) and R22(9) ring motifs, resulting in supramolecular [001] chains. The crystal structure also features weak π–π stacking [centroid–centroid distance = 3.5943 (9) Å] and C—H...π interactions