title: Antileishmanial and Cytotoxic Activity of Some Highly Oxidized Abietane Diterpenoids from the Bald Cypress, Taxodium distichum.
abstract: Two new compounds, namely, a para-benzoquinone ring-containing abietane (1) and a para-benzoquinone ring-containing 7,8-seco-abietane (2), and 14 other known highly oxidized abietane diterpenoids (3-16) were isolated from an extract prepared from the cones of Taxodium distichum, collected in central Ohio. The active subfraction from which all compounds isolated in this study were purified was tested in vivo using Leishmania donovani-infected mice and was found to dose-dependently reduce the parasite burden in the murine livers after iv administration of this crude mixture at 5.6 and 11.1 mg/kg. The structures of 1 and 2 were established by detailed 1D- and 2D-NMR experiments, HRESIMS data, and electronic circular dichroism studies. Compounds 3 and 4 were each fully characterized spectroscopically and also isolated from a natural source for the first time. Compounds 2-16 were tested in vitro against L. donovani promastigotes and L. amazonensis intracellular amastigotes. Compound 2 was the most active against L. amazonensis amastigotes (IC50 = 1.4 μM), and 10 was the most potent against L. donovani promastigotes (IC50 = 1.6 μM). These compounds may be suggested for further studies such as in vivo experimentation either alone or in combination with other Taxodium isolates.
authors.affiliation: Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University , 500 West 12th Avenue, Columbus, Ohio 43210, United States.
authors.forename: C Benjamin
authors.initials: CB
authors.lastname: Naman
authors.affiliation: Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University , 500 West 12th Avenue, Columbus, Ohio 43210, United States.
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Gromovsky
authors.affiliation: Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University , 500 West 12th Avenue, Columbus, Ohio 43210, United States.
authors.forename: Cory M
authors.initials: CM
authors.lastname: Vela
authors.affiliation: Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University , 500 West 12th Avenue, Columbus, Ohio 43210, United States.
authors.forename: Joshua N
authors.initials: JN
authors.lastname: Fletcher
authors.affiliation: Department of Pathology, College of Medicine, The Ohio State University , 320 West 10th Avenue, Columbus, Ohio 43210, United States.
authors.forename: Gaurav
authors.initials: G
authors.lastname: Gupta
authors.affiliation: Department of Pathology, College of Medicine, The Ohio State University , 320 West 10th Avenue, Columbus, Ohio 43210, United States.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Varikuti
authors.affiliation: Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University , 500 West 12th Avenue, Columbus, Ohio 43210, United States.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University , 500 West 12th Avenue, Columbus, Ohio 43210, United States.
authors.forename: Emilia M
authors.initials: EM
authors.lastname: Zywot
authors.affiliation: Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University , 500 West 12th Avenue, Columbus, Ohio 43210, United States.
authors.forename: Heebyung
authors.initials: H
authors.lastname: Chai
authors.affiliation: Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University , 500 West 12th Avenue, Columbus, Ohio 43210, United States.
authors.forename: Karl A
authors.initials: KA
authors.lastname: Werbovetz
authors.affiliation: Department of Pathology, College of Medicine, The Ohio State University , 320 West 10th Avenue, Columbus, Ohio 43210, United States.
authors.forename: Abhay R
authors.initials: AR
authors.lastname: Satoskar
authors.affiliation: Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University , 500 West 12th Avenue, Columbus, Ohio 43210, United States.
authors.forename: A Douglas
authors.initials: AD
authors.lastname: Kinghorn
mesh_terms: D045784:Abietanes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D000818:Animals; D016227:Benzoquinones / Q000737:chemistry; D020128:Inhibitory Concentration 50; D007893:Leishmania donovani / Q000187:drug effects*; D051379:Mice; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D009820:Ohio; D010084:Oxidation-Reduction; D032489:Taxodium / Q000737:chemistry*
chemical_list: C000610218:7-O-methyltaxoquinone; D045784:Abietanes; D016227:Benzoquinones; C000610219:taxotrione; C004532:quinone