Work

Bioactivity-Guided Isolation of Totarane-Derived Diterpenes from Podocarpus neriifolius and Structure Revision of 3-Deoxy-2α-hydroxynagilactone E

Year: 2019

Type: article

Abstract: Podocarpus neriifolius D. Don (Podocarpaceae) is a tree growing in south Asian countries, such as Nepal and Vietnam, in Eastern China, and in the Pacific Islands [ 1 ]. While the wood of this plant is used as timber for furniture and in paper-making, its edible fruits are consumed raw or cooked, and decoctions from its leaves are used in folk medicine to relieve rheumatism and painful joints [ 2 ]. Plants of the genus Podocarpus have been reported to exhibit a variety of biological activities ranging from plant-growth regulation [ 3 , 4 ] to antibacterial [ 5 ] and antiproliferative [ 6 , 7 , 8 , 9 ] effects. These activities have been attributed mainly to their chemotaxonomic markers, the nor- and bisnorditerpene dilactones, referred to as the podolactones or nagilactones [ 10 , 11 ]. The podolactones exist in three main classes (types A-C) depending on the conjugated system between the B and C rings. As such, type A possesses a [8(14), 9(11)-dienolide] moiety, while types B and C are characterized by the presence of [7 α ,8 α -epoxy-9(11)-enolide] and [7(8), 9(11)-dienolide] groups, respectively (Fig. 1 ) [ 7 , 10 , 12 ]. P. neriifolius produces several podolactones including the cytotoxic nagilactone C [ 13 ], the sulfur containing derivatives, podolactones C and D [ 14 , 15 , 16 ], and more recently a new cyclopeptide, neriitide A and the lignan, neriilignan, were reported from the leaves of this plant [ 17 ] (Fig. 1 ). In a continuing effort to discover potential lead anticancer agents from natural sources as part of a multidisciplinary program project grant [ 18 ], a root sample of P. neriifolius was investigated, resulting in the purification of one new ( 2 ) and three known ( 1 , 3 and 4 ) B-type podolactones, as well as three known totarane-type diterpenes ( 5–7 ). The isolation and structure determination of the obtained isolates, along with their antiproliferative properties against a panel of four human cancer cell lines (ovarian, breast, colon, and melanoma) are reported herein. Moreover, for the first time, in vivo evaluation of the major isolate, inumakilactone A ( 3 ), in a murine hollow fiber assay was conducted and described in the present study.

Source: Natural Products and Bioprospecting

DOI: 10.1007/s13659-019-0198-x