Synthesis of novel trans-2,3-dihydrofuran-pyrazole conjugates through molecular hybridization: molecular docking insights and evaluation of anti-inflammatory and anti-malarial activities.

A series of some new trans 2,3-dihydrofuran-linked pyrazole hybrids were synthesized from a convenient one-pot methodology. This procedure employs a sequential one-pot, two-step tandem reaction starting from pyridine, formylpyrazole, dimedone, and phenacyl bromide, with triethylamine serving as the base and proceeds efficiently in acetonitrile. The recently synthesized compounds were characterized through (1)H and (13)C NMR, Mass and IR spectroscopy and evaluated for their anti-inflammatory and anti-malarial potentials. Among the evaluated compounds, the derivative 4l, featuring a bromo group on the acetylphenyl and a methoxy group on the formylpyrazole phenyl ring, demonstrated potent anti-inflammatory activity with an IC(50) value of 7.12 ± 0.03 μM. This potency was comparable to that of the standard drug diclofenac sodium (IC(50) = 6.44 ± 0.02 μM). Additionally, 4l exhibited moderate anti-malarial properties with an IC(50) value of 1.66 ± 0.04 μM, with respect to the reference drug quinine (IC(50) = 0.26 ± 0.03 μM). Molecular docking studies were also performed to observe molecular interaction between the synthesized molecules and Enoyl-acyl-carrier-protein reductase (PDB ID: 1NHG) and Cyclooxygenase-2 inhibitors (3LN1). These studies provided valuable insights into the binding modes and affinities of the synthesized compounds, which may inform the design of future therapeutic agents.