Studies On The Natural Products From Seven Medicinal Plants

Seven medicinal plants, Melia toosendan, Melia azedarach, Notopterygium incisum, Sonneratia caseolaris, Sonneratia ovate, Ailanthus altissima and Brucea javanica have been chemically investigated. A total of 106 different compounds were obtained and characterized as thirty triterpenoids, eleven limonoids, twelve-one steroids, nineteen coumarins, ten sesquiterpenoids, three flavonoids, six phenylpropanoids, four polyacetylenes and two diphenyls. Among them,37 compounds were new. Their structures were extensively identified on the basis of spectroscopic methods, chemical transformations, single-crystal X-ray diffraction analysis and molecular modeling studies. Biological activities tests showed that some compounds were klotho (an aging-suppressor gene) promoter activators, while other compounds exhibited significant anti-proliferative effects. For isolated anti-proliferative linear furocoumarins, their structure-activity relationship (SAR) was briefly discussed and the primary mechanism was carried out using flow cytometry (FCM).1. Thirty-five compounds, including sixteen tetracyclic triterpenoids, eleven limonoids and eight steroids were isolated from Melia toosendan (Meliaceae). Among them, seventeen were new:twelve new tetracyclic triterpenoids (1-12), four new limonoids (25-35) and one new steroid (13). The relative configuration of meliasenins I (1) was determined by its single-crystal X-ray diffraction analysis. The biosynthetic pathway of the isolated peroxylated compounds was briefly discussed. Most compounds were tested for their insecticidal and cytotoxic effects, and compounds 1-10,13-17 and 22 were found to show significantly cytotoxic against U20S human osteosarcoma and MCF-7 human breast cancer cells.2. The barks and the leaves of the Melia azedarach have been investigated. Two new triterpenoids (36,37), two new steroids (38,39), one new naturally occurring steroid (40) along with eleven related known compounds (14,15,18-21,23,41-44) were isolated from the barks. Among them, compound 36 was a novel triterpenoid bearing a rare 21,24-cyclopentane ring in the side chain, and its relative configuration was determined by density functional theory (DET) calculations together with the NMR analysis. In addition, the NMR data of the steroid 40 was reported for the first time and its relative configuration was confirmed by single-crystal X-ray diffraction analysis. Compounds 14,15,23,37-39,41,43,45,46 and 48 showed significantly cytotoxic effects against A549, H460 and HGC27 cell lines. At the same time, three new (45-47) and several known (48-50) steroids were isolated from the leaves of M. azedarach. Some of the isolates showed moderate cytotoxic effects against A549, H460 and U251 cell lines.3. The chloroform extract of Notopterygium incisum (Qiang-Huo) was preliminarily found to activate the klotho gene promoter. Bioassay-guided isolation and purification led to the identification of thirty-four compounds, including eventeen coumarins, ten sesquiterpenoids and seven other compounds from the dried rhizomes of N. incisum. Among them, compounds 51 and 52 were new linear furocoumarins, while compounds 53 and 54 were new guaiane-type sesquiterpenoids. This is the first time that sesquiterpenoids were isolated and characterized from N. incisum. Compound 77 was found to be a potential klotho gene promoter activator.Recently, klotho gene was also reported to be a cancer inhibitor gene and has the ability to regulate the IGF-1 and FGF signal pathways of human breast cancer cells. Thus, all isolates from N. incisum were evaluated for their anti-proliterative effect and some compounds showed cytotoxicities against HepG2, MCF-7 and C6 cell lines. The SAR was briefly discussed and revealed that linear furocoumarins bearing a monoterpenyloxyl side chain with a free hydroxyl group were cytotoxic. Notopol (64) and notopterol (66) were selected to study their anti-proliferative mechanism using flow cytometry and found that after treated with these two compounds, MCF-7 cells accumulated in the G2/M phase, and were mostly apoptotic in this phase.4. Nine known compounds were obtained and determined from Sonneratia caseolaris and seven known compounds were isolated from S. ovate. The structures included diphenyls, triterpenoids, nor-lignans, phenylpropanoids and flavonoids. Compounds 85,86 and 89 were found to show moderate cytotoxic activity against C6 cells. The nor-lignans (85,86) and 6H-benzo[b,d]pyran-6-one derivatives (87,88) may tentatively be considered as taxonomic markers for Sonneratia genus and the biosynthesis of the isolates were discussed herein.5. Ailanthus altissima and Brucea javanica are two species belonging to Simarubaceae. In this study, twelve compounds were isolated and determined from A. altissima. Among them, compounds 95 and 96 were two new coumarins.97,98 and 99 were three new tetracyclic triterpenoids. Meanwhile, five known compounds, including four steroids and a lignanoids have been so far obtained and determined from B. javanica.