Reshma Kayarmar

Design, synthesis and characterization of new 1,2,3-triazolyl pyrazole derivatives as potential antimicrobial agents via a Vilsmeier–Haack reaction approach

The synthesis of a new series of 3-{5-methyl-1-[2-methyl-3-(trifluoromethyl) phenyl/substituted phenyl]-1H-1,2,3-triazol-4-yl}-1-(aryl)-1H-pyrazole-4-carbaldehyde compounds (5a–n) was carried out via a Vilsmeier–Haack formylation of 4-{(1E)-1-[2-(aryl) hydrazinylidene]ethyl}-5-methyl-1-[2-methyl-3-(trifluoromethyl)phenyl/substituted phenyl]-1H-1,2,3-triazole (4a–n) with a phosphorous oxychloride and DMF mixture. The newly synthesized compounds were characterized using IR, 1H NMR, 13C NMR, mass spectral data and elemental analysis. The newly synthesized compounds were screened for their in vitro anti-bacterial, anti-fungal and anti-oxidant activities. Some of the synthesized compounds displayed a broad spectrum of antimicrobial activities and moderate to good anti-oxidant activities. The anti-bacterial results were further supported by in silico molecular docking studies of these compounds for the inhibition of E. coli MurB enzyme (PDB code: 2MBR) and showed a minimum binding energy and good affinity towards the active pocket comparable with the standard drug Ciproflaxin. Thus, they may be considered as good inhibitors of the E. coli MurB enzyme (PDB code: 2MBR).

Synthesis of azabicyclo[4.2.0]octa-1,3,5-trien-8-one analogues of 1H-imidazo[4,5-c]quinoline and evaluation of their antimicrobial and anticancer activities

In search of new and efficient antimicrobial and anticancer agents based on the imidazoquinoline structural framework, a series of novel 7-(1-isobutyl-1H-imidazo[4,5-c]quinolin-4-yl)-7-azabicyclo[4.2.0]octa-1,3,5-trien-8-ones (8a–f) were synthesized from the corresponding 2,4-dihydroxoquinoline derivative through multistep reactions. The structures of these compounds were established by IR, 1H NMR, 13C NMR and mass spectral studies. The 7-(1-isobutyl-1H-imidazo[4,5-c]quinolin-4-yl)-7-azabicyclo[4.2.0]octa-1,3,5-trien-8-one (8a–f) analogues were evaluated for their in vitro antimicrobial activity by serial dilution method minimum inhibitory concentration (MIC). The derivatives 8c, 8e and 8f exhibited excellent antibacterial activity comparable to the parent drug ampicillin with MIC value. Compounds 7a–f and 8a–f were also assessed for their cytotoxic activity (IC50) against HeLa cells using the Trypan blue exclusion assay method. The compounds 7c and 8b displayed potential anticancer activity. In a molecular docking study, these compounds showed minimum binding energy and good affinity towards the active pocket. They are believed to be good inhibitors of β-tubulin. The results of these studies provided evidence that 7-(1-isobutyl-1H-imidazo[4,5-c]quinolin-4-yl)-7-azabicyclo[4.2.0]octa-1,3,5-trien-8-one (8a–f) derivatives are a promising class of antibacterial and anticancer agents.

4-Chloro-benzaldehyde (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).

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.

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

In the title compound, C(16)H(20)N(4), the 1H-imidazo[4,5-c]quinoline ring system is approximately planar, with a maximum deviation of 0.0719 (15) Å. An intra-molecular C-H⋯N hydrogen bond contributes to the stabilization of the mol-ecule, forming an S(6) ring motif. In the crystal, the mol-ecules are stacked along the b axis through weak aromatic π-π inter-actions between benzene and imidazole and benzene and pyridine rings [centroid-centroid distances = 3.6055 (10) and 3.5342 (10) Å, respectively].

Synthesis, characterization and pharmacological evaluation of some new 1,3,4-oxadiazole derivatives bearing 3-chloro-2-fluoro phenyl moiety

A new series of 2-(3-chloro-2-fluorophenyl)-5-aryl-1,3,4-oxadiazole (3a–j) and 2-(aryl sulfanyl)-5-(3-chloro-2-fluorophenyl)-1,3,4-oxadiazole (5a–e) were synthesized via a multistep reaction from 3-chloro-2-fluoro benzoic acid. The newly synthesized compounds were characterized by IR, 1H NMR, 13C NMR, mass spectral data and elemental analysis. They were also screened for their in vivo anti-convulsant and anti-inflammatory activities. Some of them exhibited significant biological activities and were well supported by in silico molecular docking studies for the inhibition of cyclooxygenase-2 (PDB ID: 1CX2) and voltage-gated sodium channels (PDB ID: 4F4L) comparable with the standard drugs. Thus, they were believed to be good inhibitors of cyclooxygenase-2 (PDB ID: 1CX2) and voltage-gated sodium channels (PDB ID: 4F4L).

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 R 1 2(6) and R 2 2(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.

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.

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.