Antiprolif-erative Constituents of Roots of Podocarpus falcatus (Thunb.) R.Br. ex Mirb

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Addis Ababa University


Once thought of as the disease of the developed, cancer nowadays is becoming the prob-lem of every nation across the globe claiming millions of lives every year. Incidence, and thus prevalence, is increasing every year due to adoption of lifestyle factors that are known to be major cancer risk factors. Making things worse is the development of MDR to the known effective anticancer drugs. Moreover, the currently available drugs are cost-ly and are associated with severe side effects. Thus, discovering new anticancer drugs with new and safe modes of action is urgently needed. Natural products derived from medicinal plants are well-known contributors of clinically useful anticancer drugs; suffice to mention taxol, the Vinca alkaloids, podophyllotoxin and camptothecin and their de-rivatives. Relying on traditional medicines for most of their health needs, Ethiopians use various plants for prevention and treatment of cancer. For example, the roots of Podocar-pus falcatus are used as “anticancer” remedies in some parts of Ethiopia, which formed the basis of the present study to isolate the “responsible” “bioactive” compounds. Bioassay guided fractionation using the human colorectal adenocarcinoma (HT-29) cell line of the methanol extract of dried roots of P. falcatus (Podocarpaceae) led to the isola-tion of two new type C nagilactones, 16-hydroxy nagilactone F (PF-1) and 2β,16-dihydroxy nagilactone F (PF-3) and a new totarane-type bisditerpenoid 7β-hydroxy mac-rophyllic acid (PF-2), along with the seven known compounds: inumakinol D (28), mac- rophyllic acid (37), nagilactone D (41), ponasterone A (94), 2β-hydroxy nagilactone F (108), nagilactone I (109), and 15-hydroxy-nagilactone D (110). The structures of the new compounds were determined by 1D and 2D-NMR, HRESIMS and by comparison with the reported spectroscopic data of their congeners. The orientation of the hydroxyl group at C-2 of 108 and 109 was revised to be β based on evidence from detailed analysis of 1D and 2D-NMR data and single crystal X-ray diffraction studies. Among the isolated compounds the nagilactones, including the new dilactones 16-hydroxy nagilactone F (PF-1) and 2β,16-dihydroxy nagilactone F (PF-3), were the most active (ED50 0.3–5.13 μM range) against the HT-29 cell line, whereas the bisditerpenoids (PF-2 and 37) and the other known compounds 28 and 94 were inactive. The presence of bioactive nagilactones in P. falcatus supports its traditional use.



Antiproliferative;Podocarpus falcatus (Thunb.) R.Br. ex Mirb