Dihydrostilbenes and diarylpropanes: Synthesis and in vitro pharmacological evaluation as potent nitric oxide production inhibition agents.

An efficient synthesis of dihydrostilbenes (1-5) and diarylpropanes (6-10) is achieved from the commercially available starting materials and Wittig-Horner reaction, Claisen-Schmidt condensation and hydrogenation as key steps. Later, their nitric oxide (NO) production inhibition effects were evaluated in lipopolysaccharide (LPS)-induced RAW-264.7 macrophages as an indicator of anti-inflammatory activity. All the tested compounds significantly decreased NO production in a concentration-dependent manner except compounds 2, 6 and 8 and did not show notable cytotoxicity except compound 1. Two compounds i.e., compound 9 (hindsiipropane B) (100%; IC=1.84μM) possessed the most potent NO inhibitory activity which was even stronger than the positive control, L-NMMA (90.1%; IC=2.73μM) followed by compound 4 (75.5%; IC=2.98μM) at 10μM concentration and this finding was also further correlated by suppressed expression of LPS stimulated inducible NO synthase. Our study revealed that compound 9, a 1,3-diarylpropane scaffold with 3″,4″-dimethoxyphenyl and 3',4'-dihydroxy-2'-methoxyphenyl motifs could be considered as potential compound or lead compound for further development of NO production-targeted anti-inflammatory agents.