Thesis (Ph.D.)--Chulalongkorn University, 2009

To search for bioactive compound isolated from Thai medicinal plants using ∆zdsl yeast-based assay, a unique positive-drug screening system. In the preliminary screening, four crude extracts of 50 medicinal herbs (Andrographis paniculata, B. pandurata, K. parviflora and Syzygium cinereum) exhibited strong positive results on calcium signaling inhibition in the assay. Two potent positive plants of Zingiberaceae family, B. pandurata and K. parviflora, were chosen for further fractionation followed by activity guided yeast-based assay. The CH2Cl2 extracts of these plants were isolated by chromatographic techniques and seven known flavonoid compounds were obtained. Structures of the compounds were elucidated by spectroscopic techniques. Pinostrobin (A), alpinetin (B) and pinostrobin chalcone (C) were isolated from B. pandurata and 5-hydroxy-3,7-dimethoxyflavone (D), 5-hydroxy-7-methoxyflavone (E), 5-hydroxy-3,7,4'-trimethoxyflavone (F) and 5,7-dimethoxy-flavone (G) were found in K. parviflora. Compound A and D exhibited strong positive and non-toxic to the yeast cells so they were chosen for further biological studies. For the study of A and D on finding the target molecules in the calcium signaling pathway, the target molecules of these two compounds were Swe1 (ortholog of mammalian Wee1) and MCK1 (homolog of mammalian GSK3), respectively. The two compounds exhibited moderate anti-inflammatory activity on carrageenin-induced paw edema in rat with % inhibition values of 43.71 and 42.2, respectively. Moreover, Compound A also exhibited the cytotoxicity with MTT assay on Jukat, A375 and Kato III human cancer cell lines with IC50 value of 56, 67 and 86 µM, respectively. Compound D moderately inhibited 6 strains of Helicobacter pylori with the MIC value of 0.84-6.71 µM