Isolation, Identification Of Sinensetin From Orthosiphonis Spiralis (Lour.) Merr., And Investigation Of Its Anti-Cancer Activity Using Molecular Docking And Pharmacophore

Abstract

Isolation and identification of sinensetin from powder extract of Orthosiphonis spiralis (Lour.) Merr., and the interaction between drug candidates presented in O.spiralis and three receptors such as 17beta-HSD1, ErbB2, and PKB/Akt-2 via molecular docking and pharmacophore were investigated. The extraction of sinensetin was performed through various stages including liquid-liquid extraction with dichloromethane solvent, classic column chromatography (CC) with gradient elution, and preparative high-performance liquid chromatography (prep-HPLC) with acetonitrile-water (41:59). The presence of sinensetin was examined by dichloromethane-methanol (95:5) as a developing solvent of thin-layer chromatography (TLC) method under UV 365 nm with a blue fluorescent band, UV 254 nm with a quenching band and 10% sulfuric acid in ethanol with a yellow band. Alternatively, sinensetin can be detected by high-performance liquid chromatography (HPLC) with mobile phase acetonitrile-water (50:50) at the retention time around 14 minutes. The structure elucidation was shown in MS, NMR spectroscopy and UV-Vis spectra, which absorbs at maximum wavelength of 215 nm. Regarding anti-breast cancer activity, totally 24 drug candidates showed the best docking score towards three proteins, which was lower than -8.0 kcal/mol. For pharmacophore features, all the ligands well-contacted to binding pocket of receptors comprising Ser 142, Tyr 155, Phe 192, Val 225, Phe 259, Leu 149, Met 279, Val 196, Phe 226, Met 193 in 17beta-HSD1; Ser 442, Asn 281, Thr 6, Thr 2, Tyr 282, Leu 292, Leu 415 in ErbB2; and Lys 277, Arg 6, Thr 162, Ser 9, Thr 292, Val 166, Met 282, Met 229 in PKB/Akt-2. These results revealed that anti-breast cancer property might possibly result from the presence of flavonoid and triterpenes family including sinensetin in O.spiralis. Keywords: Orthosiphonis spiralis (Lour.) Merr Sinensetin Polymethoxyflavones Breast cancer Molecular docking