Synthesis, Antiproliferative Evaluation, and Molecular Docking Study of Novel Longifolene‐Derived Tetraline Fused Thiazole‐Amide Derivatives

Abstract

AbstractTwenty novel longifolene‐derived tetraline fused thiazole‐amide compounds were synthesized from longifolene, a renewable natural resource. Their structures were characterized by FT‐IR, NMR, ESI‐MS, and elemental analysis. The in vitro antiproliferative activity of these compounds against SK‐OV‐3 ovarian cancer cell lines, MCF‐7 human breast cancer cell lines, HepG2 human liver cancer cell lines, A549 human lung adenocarcinoma cell lines, and T‐24 human bladder cancer cell lines was tested by MTT assay. Compounds 6a–6c displayed significant and broad‐spectrum antiproliferative activity against almost the tested cancer cell lines with IC50 in the range of 7.84 to 55.88 μM, of which compound 6c exhibited excellent antiproliferative activities with 7.84 μM IC50 against SKOV‐3, 13.68 μM IC50 against HepG2, 15.69 μM IC50 against A549, 19.13 μM IC50 against MCF‐7, and 22.05 μM IC50 against T‐24, showing better and broad‐spectrum antiproliferative effect than that of the positive control 5‐FU. Furthermore, the action model was analyzed by the molecular docking study. Some intriguing structure‐activity relationships were found and discussed herein by DFT theoretical calculation.