Abstract

CHEMICAL AND BIOLOGICAL STUDIES OF SOME NATURALLY OCCURRING FUROCOUMARINS

*Sally S. El-Nakkady, Hanaa F.Roaiah, Weam S.El-Serwy, Fatma Bassyouni, A.M.Soliman.

Abstract

Furocoumarins and their related compounds are a plentiful source for drugs that are candidates in relation to their safety and efficiency. The present investigation is concerned with the synthesis, chemical study and characterization of new furocoumarin derivatives with the objective of discovering novel and potent anticancer agents. This challenging goal prompted us to diversify the reactions in order to obtain end products with different functional groups. Friedel-Craft,s acetylation of I,II,III,IV,V and VI namely Xanthotoxin, 4-methoxy-5- hydroxyl psoralen, 4,5-dimethoxy psoralen, 4,9-dimethoxy-5-hydroxy psoralen, 4,5,9-trimethoxy psoralen, and imperatorin yielded the acetyl compounds (VII, VIII, IX, X, XI,XII, XIII and XIV) respectively. Aldol condensation of (VII) with aromatic and/ or hetero aldehydes formed chalcones (XV) and (XVI). Bromination of xanthotoxin I in acetic acid yielded the bromo derivative (XVII), which reacted with alkaline dimethyl sulfate, aluminum chloride, acetic anhydride, hydrazine hydrate, malononitrile, ethyl cyanoacetate and sodium ethoxide to give (XVIII, XIX, XX, XXI, XXII, XXIII and XXIV) respectively. The bromo acrylic acid benzofuran (XXIV) reacted with malononitrile and or ethyl cyanoacetateto to give (XXII) and (XXIII) respectively. The Structures of the synthesized compounds were established on the basis of elemental analysis, IR, 1H NMR, Mass and spectral data. The anticancer activity of some of the synthesized compounds was evaluated against liver cancer cell lines HEPG2 that induced a moderate growth inhibition in a dose-dependent manner against HEPG2 when compared to 5-FU and DOX chemotherapy. It can be deduced from the results that compound (XVII) was the highest compound in activity when compared to the reference anticancer drug (5-FU and DOX).

Keywords: Acetylation, Bromination, Cytotoxicity, Furocoumarins, Liver cancer cell line.