Synthesis of carbohydrate-linked pentadienone derivative with antitumor properties

INTRODUCTION: Alternatives are constantly investigated in the field of oncology. In this regard, natural compounds, like curcumin, are promising because of their excellent biological activities and low toxicity1. The work aims to improve the activity and selectivity of a curcumin derivative, binding to carbohydrate. The effect of carbohydrate-bound compounds is due to the specific interactions between carbohydrates and lectins in the cancer cell wall. The receptors for carbohydrate binding have been described on the tumor cells2. RESULTS AND DISCUSSION: From L-Ramnose the total acetylation of the free OH groups was carried out. In the next step, the acetylated anomeric carbon was replaced with bromine by treatment with hydrogen bromide. Using the Helferich glycosylation, it was possible to obtain the following allylic derivative. Cleavage of the acetyl groups was performed under Zemplen deacetylation conditions, followed by the benzylation reaction, to protect the free OH groups. Deprotection of the allyl group in the presence of PdCl2 was performed successfully. From this point the respective trichloroacetoimidate derivate 8 was synthesized, with TMSOTf as Lewis acid. The association of the sugar 8 to the chalcone 1,5-bis(4-hydroxy-3-methoxyphenyl)penta-1,4-dien-3-one gave the new analogue, 9. The MTT biological assay was performed and showed IC50 of 2.66 μM, 14.94 μM, and 1.023 μM, 6.492 μM, for the 4T1, MCF7, SCC9 and SCC25 lineages respectively. CONCLUSIONS: Considering the IC50 value in μM of traditional drugs for the treatment of cancer, like doxorubicin and paclitaxel, the derivative 9 showed promise. It presented a lower value of IC50 and it is nontoxic to the normal cell lines like HUVEC and MACRF.