title: Antiproliferative Constituents of the Roots of Ethiopian Podocarpus falcatus and Structure Revision of 2α-Hydroxynagilactone F and Nagilactone I.
abstract: Bioassay-guided fractionation using the human colorectal adenocarcinoma (HT-29) cell line of the methanol extract of dried roots of Podocarpus falcatus led to the isolation of two new type C nagilactones, 16-hydroxynagilactone F (1) and 2β,16-dihydroxynagilactone F (2), and the new totarane-type bisditerpenoid 7β-hydroxymacrophyllic acid (4), along with the seven known compounds 2β-hydroxynagilactone F (3), macrophyllic acid (5), nagilactone D (6), 15-hydroxynagilactone D (7), nagilactone I (8), inumakiol D (9), and ponasterone A (10). The structures of the new compounds were determined by 1D and 2D NMR, HRESIMS, UV, and IR and by comparison with the reported spectroscopic data of their congeners. The orientation of the C-2 hydroxy group of 3 and 8 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-hydroxynagilactone F (1) and 2β,16-dihydroxynagilactone F (2), were the most active (IC50 0.3-5.1 μM range) against the HT-29 cell line, whereas the bisditerpenoids (4 and 5) and the other known compounds 9 and 10 were inactive. The presence of the bioactive nagilactones in P. falcatus supports its traditional use.
authors: †Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, Ohio 43210, United States.|‡Department of Pharmaceutical Chemistry and Pharmcognosy, School of Pharmacy, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia.
authors: Ermias Mekuria
authors: EM
authors: Addo
authors: †Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, Ohio 43210, United States.
authors: Hee-Byung
authors: HB
authors: Chai
authors: ‡Department of Pharmaceutical Chemistry and Pharmcognosy, School of Pharmacy, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia.
authors: Ariaya
authors: A
authors: Hymete
authors: ‡Department of Pharmaceutical Chemistry and Pharmcognosy, School of Pharmacy, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia.
authors: Mariamawit Yonathan
authors: MY
authors: Yeshak
authors: §Department of Chemistry and Virginia Tech Center for Drug Discovery, M/C 0212, Virginia Tech, Blacksburg, Virginia 24061, United States.
authors: Carla
authors: C
authors: Slebodnick
authors: §Department of Chemistry and Virginia Tech Center for Drug Discovery, M/C 0212, Virginia Tech, Blacksburg, Virginia 24061, United States.
authors: David G I
authors: DG
authors: Kingston
authors: †Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, Ohio 43210, United States.
authors: L Harinantenaina
authors: LH
authors: Rakotondraibe
mesh_terms: D045784:Abietanes; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D004224:Diterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D005002:Ethiopia; D019073:HT29 Cells; D006801:Humans; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D028201:Pinaceae / Q000737:chemistry*; D018517:Plant Roots / Q000737:chemistry
chemical_list: C552237:12,13-dihydroxy-8,11,13-totaratriene-6-one; C000600876:16-hydroxynagilactone F; C000600877:2beta,16-dihydroxynagilactone F; D045784:Abietanes; D000972:Antineoplastic Agents, Phytogenic; D004224:Diterpenes; C004552:nagilactone C