Novel Caffeic Acid Phenethyl Ester (CAPE) Analogues as Immunoregulatory Agents: Synthesis and SAR Study

Two novel caffeic acid phenethyl ester (CAPE) analogues, (E)-4-hydroxyphenethyl 3-(3,4-dihydroxyphenyl)acrylate (HPDHPA) and (E)-4-nitrophenethyl 3-(3,4-dihydroxyphenyl) acrylate (NPDH-PA) were synthesized according to the relationship between the antitumor activity and ClogP values of the known CAPE derivatives calculated by CambridgeSoft Corporation Chemoffice 8.0. The effects of the two synthesized CAPE analogues on increasing the white blood cell (WBC) count, spleen index, thymus index and the level of nitric oxide against the immunosuppressed mice were studied. The results indicated that the immunoregulatory activity increased at the low dose of HPDHPA and NPDHPA (HPDHPA group > NPDHPA group > CAPE group) (3 mg/kg), and the activity increased with the decrease of ClogP. In addition, the immunoregulatory activity was affected by other chemical parameters like total energy at high dose of the novel CAPE analogues.