Bioactive 6S‑Styryllactone Constituents of Polyalthia parvif lora Jing-Ru Liou, † Tung-Ying Wu, † Tran Dinh Thang, ‡ Tsong-Long Hwang, § Chin-Chun Wu, † Yuan-Bin Cheng, † Michael Y. Chiang, ⊥ Yu-Hsuan Lan, ∥ Mohamed El-Shazly, † Shwu-Li Wu, ⊗ Ludger Beerhues, □ Shyng-Shiou Yuan, # Ming-Feng Hou, # Shu-Li Chen, † Fang-Rong Chang,* ,†,# and Yang-Chang Wu* ,†,∥,$,Δ † Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan ‡ Department of Chemistry, Vinh University, Vinh City 182, Vietnam § Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan ⊥ Department of Chemistry, National Sun Yat-sen University, Kaohsiung 804, Taiwan ∥ School of Pharmacy, College of Pharmacy, China Medical University, Taichung 404, Taiwan ⊗ Center of General Studies, National Kaohsiung Marine University, Kaohsiung 811, Taiwan □ Institute of Pharmaceutical Biology, Technische Universitä t Braunschweig, 38106 Braunschweig, Germany # Translational Research Center and Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan $ Chinese Medicine Research and Development Center, China Medical University Hospital, Taichung 404, Taiwan Δ Center for Molecular Medicine, China Medical University Hospital, Taichung 404, Taiwan * S Supporting Information ABSTRACT: Parvistones A−E(1−5), five new styryllactones possessing a rare α,β-lactone moiety and a 6S configuration, were isolated from a methanolic extract of Polyalthia parvif lora leaves. The structures and the absolute configuration of the isolates were elucidated using NMR spectroscopy, specific rotation, circular dichroism, and X-ray single-crystal analysis. Compounds 8, 9, 11, and 12 were isolated for the first time. The results were supported by comparing the data measured to those of 6R-styryllactones. Moreover, a plausible biogenetic pathway of the isolated compounds was proposed. The structure−activity relationship of the com- pounds in an in vitro anti-inflammatory assay revealed the 6S-styryllactones to be more potent than the 6R derivatives. However, the effect was opposite regarding their cytotoxic activity. In addition, 6S-styrylpyrones isolated showed more potent anti-inflammatory and cytotoxic activity when compared to the 1S-phenylpyranopyrones obtained. S everal classes of secondary metabolites have been isolated from the genus Polyalthia (Annonaceae) including acetogenins, 1 ter- penoids, 2 alkaloids, 3 benzopyrans, 4 2-substituted furans, 5 and styr- yllactones. 6 Some of these compounds were found to possess potent cytotoxic and anti-inflammatory activities. 2,7 In general, Polyalthia spp. contain a diverse group of secondary metabolites; however, not all species belonging to this genus have been thoroughly inves- tigated. Among the little-studied species is Polyalthia parvif lora Ridl. This plant is a shrubby tree that can be found in different Asian countries including Thailand, Malaysia, and Cambodia. It is considered a preferred food for domesticated and wild herbivores. 8 Traditional healers in Asia use a water decoction of P. parvif lora to treat bodily discomfort. 9 Only one study has investigated the phytochemical constituents of P. parvif lora, reporting the isolation of p-coumarate, p-hydroxyphenylethyl ferulate, dehydrodiscret- amine, and (−)-discretamine. 9 Due to the scarcity of reports on P. parvif lora, an extensive phytochemical and biological investigation on the secondary metabolite content of this species was initiated. The chromatographic purification of the methanolic extract of P. parvif lora leaves led to the isolation of 13 6S-styryllactones (1−13), which can be subdivided into 6S-styrylpyrones (1−3 and 7−13) and 1S-phenylpyranopyrones (4−6). Details on the isolation, structure elucidation, a plausible biogenetic route, and biological activities of these two classes of secondary metabolites are presented herein. Moreover, the preliminary structure− activity relationships of 1−13, in terms of their anti-inflammatory and cytotoxic activities, are discussed. ■ RESULTS AND DISCUSSION The 1 H NMR spectroscopic data of the 6S-styrylpyrones, 1−3, were closely comparable to one another except for certain distinguishing features (Table 1). The HRESIMS data of 1 Received: June 6, 2014 Article pubs.acs.org/jnp © XXXX American Chemical Society and American Society of Pharmacognosy A dx.doi.org/10.1021/np5004577 | J. Nat. Prod. XXXX, XXX, XXX−XXX