Anticancer Activity of 3,5-Bis(dodecyloxy)benzoate-PAMAM Conjugates with Indomethacin or Mefenamic acid



The aim of the present investigation was the synthesis of 3,5-bis(dodecyloxy)benzoate -PAMAM conjugates with indomethacin an mefenamic acid to examine their anticancer activity.



The synthesis of conjugates with nonsteroidal anti-inflammatory drugs could be improve their activity with less toxicity and these compounds could be used for the treatment of cancer.



The synthesis of 3,5-bis(dodecyloxy)benzoate -PAMAM conjugates with indomethacin or mefenamic acid to examine their anticancer activity.



The anticancer activity was studied of the conjugates against six human cancer cells U-251 (human glioblastoma), PC-3 (human prostatic adenocarcinoma), K-562 (human chronic myelogenous leukemia cells), HCT-15 (human colorectal adenocarcinoma), MCF-7 (human mammary adenocarcinoma), SKLU-1 (human lung adenocarcinoma) and the COS-7 African green monkey (as a control) cell lines. The conjugates with indomethacin and mefenamic acid were characterized by 1H, 13C NMR one- and two-dimension spectroscopy.



All the conjugates synthetized with indomethacin or mefenamic acid showed anticancer activity against all the human cancer cell lines. The first generation of indomethacin conjugates showed better activity against PC-3 cell line than the second generation. But the second generation with indomethacin showed better activity against PC-3 (human prostatic adenocarcinoma) than the first generation. The second generation conjugate with mefenamic acid had strong selectivity to PC-3 (human prostatic adenocarcinoma) cells with IC50 value of 10.23±1.2 M in vitro.



In the paper, we report the synthesis and spectroscopic analyses of new indomethacin or mefenamic acid conjugates. The overall results showed that the conjugate of second generation with mefenamic acid could be a potential nanocarrier for human prostatic adenocarcinoma cancer treatment.



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