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

Twenty 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.

Synthesis of (E)/(Z)-Verbenone Oxime Ethers and Photoresponsive Behavior to Herbicidal Activity.

The accumulation of residual active herbicides in the environment can cause a series of problems. It is thus meaningful to explore a photoresponsive herbicide, whose activity can be weakened under the action of light to reduce the negative effect. To this purpose, a series of (E)/(Z)-verbenone oxime ethers were designed, synthesized, and characterized. Oxime ether groups were adopted as the trigger switches. The preliminary screening for herbicidal activity showed that some of them exhibited better or comparable effects than that of the commercial herbicide flumioxazin against Brassica campestris and Echinochloa crusgalli. Meanwhile, five pairs of the target compounds with significantly different herbicidal effects between E- and Z-forms were further investigated for their reversible isomerization reaction and the accompanying variation of herbicidal activity. As a result, the maximum conversion rates were around 50%, and the herbicidal effect of the resulting mixture of E- and Z-isomers decreased outstandingly. The phototransformation mechanism of a pair of isomers (E)-4a and (Z)-4a was preliminarily explored. Besides, a reasonable and effective 3D-quantitative structure-activity relationship model (r2 = 0.984 and q2 = 0.571) was established and the binding mode was also investigated by molecular docking.