Synthesis Of The Analogues Of Higher Fatty Acids And Their Anti-Tumor Activities

Objective: To synthesize the analogues of higher fatty acids by structural modification;To screen anti-tumor active compounds through the anti-tumor testing in vitro; To optimizate the synthetic conditions. To study the anti-tumor effect and dose-effect relationship of the screened compound in vivo.Methods: 1. Behenic acid, erucic acid, arachidic acid, arachidonic acid were used as material to synthesized eight analogues of higher fatty acids and their structures were identified by 1H-NMR, 13C-NMR. 2. Anti-tumor activities in vitro selection: the inhibitions of BEL-7404 cells of the new compounds were observed, some active compounds were screened. The toxicity of the resistant cell line of TCA8113 was detected through MTT. The reversal effect on the resistant cell line of TCA8113 of compound UFA301was detected through MTT. 3. The synthetic conditions of the compound UFA301 were optimizated to increase yield. 4. The acute toxicological studies of the active compound was carried on to determine the scope of its security administration. 5. Anti-tumor effect in vivo: The S180 ascites tumor model in Kunming mice was established, The life extension rate and weight change of the treated group were studied . The anti-tumor effect of drug was studied in vivo.Results: 1. Eight designed compounds were synthesized and structural identified. 2. The tumor inhibition rate of compounds UFA301 and UFA306, above the concentration of 400μg/mL were obvious in vitro. The compound UFA301 had no significant toxicity on the resistant cell line of TCA8113, but had significant reversal effect on the resistant cell line of TCA8113. Compound UFA301 reversed TCA/ADM cells that resisted 0.1μg/ml ADM, the reverse fold (RF) was 3.67, the relative reversal effect was 73.12%, and in positive group the reverse fold (RF) was 4.47, the relative reversal effect was 78.04%. 3. The synthetic way of compound UFA301 optimized yield of 85% or more, could meet the needs for the post-test. 4. The compound UFA301 was proved by the acute toxic test that over 100mg/kg the toxicity to Kunming mice was not obvious. 5. The survival time of S180 ascites-tumour bearing mice was extended by compound UFA301, but had no statistical difference compared to the control group in vivo.Conclusions: Eight designed compounds are synthesized. The compounds UFA301 , UFA306 have a certain prosect above the concentration of 400μg/mL in the anti-tumor expriment in vitro, the compound UFA301 has significant reversal effect on the resistant cell line of TCA8113. And the experiments in vivo show that, the compound of UFA301 has a low toxicity. And the survival time of S180 ascites tumour bearing mice is extended by compound UFA301 with a trend.