Abstract
Antitubercular bioassay-guided fractionation of the n -hexane- and CH2 Cl2 -soluble extracts of the above-ground biomass and roots of Valeriana laxiflora led to the isolation of a new iridolactone, (4R ,5R ,7S ,8S ,9S )-7-hydroxy-8-hydroxymethyl-4-methyl-perhydrocyclopenta[c ]pyran-1-one (1 ), and a new lignan, (+)-1-hydroxy-2,6-bis-epi -pinoresinol (2 ), along with eleven known compounds, betulin (3 ), betulinic acid (4 ), 5,7-dihydroxy-3,6,4′-trimethoxyflavone (5 ), 23-hydroxyursolic acid (6 ), oleanolic acid (7 ), tricin (8 ), ursolic acid (9 ), ferulic acid, (+)-1-hydroxypinoresinol, prinsepiol, and 5,7,3′-trihydroxy-4′-methoxyflavone.
The structures of compounds 1 and 2 were elucidated on the basis of spectroscopic evidence. The absolute stereochemistry
of 1 was determined by chemical transformations and Mosher ester procedures. In a microplate
alamar blue assay against Mycobacterium tuberculosis , compounds 2 - 9 exhibited minimum inhibitory concentrations (MIC) of 15.5 - 127 μg/mL, while the
other isolates were regarded as inactive (MIC > 128 μg/mL). In addition, all the isolates
were tested for cytotoxicity against African green monkey Vero cells in order to evaluate
their selectivity potential.
Key words
Valeriana laxiflora
- Valerianaceae - iridolactone - lignan - triterpene - antimycobacterial activity
- cytotoxicity
References
1 Hoffmann A, Liberona F, Muñoz M, Watson J. Plantas Altoandinas en la Flora Silvestre
de Chile. Santiago, Chile; Ediciones Fundación Claudio Gay 1998: p. 178
2
Timmermann B N, Wächter G, Valcic S, Hutchinson B, Casler C, Henzel J. et al .
The Latin American ICBG: the first five years.
Pharm Biol.
1999;
37 (suppl.)
35-54
3
Collins L, Franzblau S G.
Microplate alamar blue assay versus BACTEC 460 system for high-throughput screening
of compounds against Mycobacterium tuberculosis and Mycobacterium avium
.
Antimicrob Agents Chemother.
1997;
41
1004-9
4
Ohtani I, Kusumi T, Kashman Y, Kakisawa H.
High-field FT NMR application of Mosher’s method. The absolute configurations of marine
terpenoids.
J Am Chem Soc.
1991;
113
4092-6
5
Su B N, Park E J, Mbwambo Z H, Santarsiero B D, Mesecar A D, Fong H HS. et al .
New chemical constituents of Euphorbia quinquecostata and absolute configuration assignment by a convenient Mosher ester procedure carried
out in NMR tubes.
J Nat Prod.
2002;
65
1278-82
6
Poehland B L, Carte B K, Francis T A, Hyland L J, Allaudeen H S, Troupe N.
In vitro antiviral activity of dammar resin triterpenoids.
J Nat Prod.
1987;
50
706-13
7
Cowan S, Stewart M, Abbiw D K, Latif Z, Sarker S D, Nash R J.
Lignans from Strophanthus gratus
.
Fitoterapia.
2001;
72
80-2
8
Tsukamoto H, Hisada S, Nishibe S.
Lignans from bark of the Olea plants. I.
Chem Pharm Bull.
1984;
32
2730-5
9
Fujita M, Nagai M, Inoue T.
Carbon-13 nuclear magnetic resonance spectral study. Effect of O -methylation of ortho -substituted phenols on the aryl carbon shielding and its application to interpretation
of the spectra of some flavonoids.
Chem Pharm Bull.
1982;
30
1151-6
10
Inada A, Yamada M, Murata H, Kobayashi M, Toya H, Kato Y. et al .
Phytochemical studies of seeds of medicinal plants. I. Two sulfated triterpenoid glycosides,
sulfapatrinosides I and II, from seeds of Patrinia scabiosaefolia Fischer.
Chem Pharm Bull.
1988;
36
4269-74
11
Bhattacharyya J, Stagg D, Mody N V, Miles D H.
Constituents of Spartina cynosuroides : isolation and 13 C-NMR analysis of tricin.
J Pharm Sci.
1978;
67
1325-6
12
Kelley C J, Harruff R C, Carmack M.
Polyphenolic acids of Lithospermum ruderale . II. Carbon-13 nuclear magnetic resonance of lithospermic and rosmarinic acids.
J Org Chem.
1976;
41
449-55
13
Kilidhar S B, Parthasarathy M R, Sharma P.
Prinsepiol, a lignan from stems of Prinsepia utilis
.
Phytochemistry.
1982;
21
796-7
14
Siddiqui S, Hafeez F, Begum S, Siddiqui B S.
Oleanderol, a new pentacyclic triterpene from the leaves of Nerium oleander
.
J Nat Prod.
1988;
51
229-33
15
Wagner H, Maurer I, Farkas L, Strelisky J.
Synthesis of polyhydroxyflavonol methyl ethers with potential cyclotoxic activity.
I. Synthesis of quercetagetin and gossypetin dimethyl ethers for the structure determination
of new flavonols from Parthenium , Chrysosplenium , Larrea , and Spinacia species.
Tetrahedron.
1977;
33
1405-9
16 Tori K, Seo S, Shimaoka A, Tomita Y. Carbon-13 NMR spectra of olean-12-enes. Full
signal assignments including quaternary carbon signals assigned by use of indirect
13 C-1 H spin couplings. Tetrahedron Lett 1974: 4227-30
17
Cantrell C L, Lu T, Fronczek F R, Fischer N H, Adams L B, Franzblau S G.
Antimycobacterial cycloartanes from Borrichia frutescens
.
J Nat Prod.
1996;
59
1131-6
18
Uesato S, Shan X, Inouye H, Shingu T, Inoue M, Doi M.
Absolute structure of gibboside, an iridoid glucoside from Patrinia gibbosa
.
Phytochemistry.
1987;
26
561-4
19 Silverstein R M, Webster F X. Spectrometric Identification of Organic Compounds. 6th
Edition New York; John Wiley & Sons, Inc. 1998: p 186
20 Cheung K K, Overton K H, Sim G A. On the conformation of δ-lactones. J Chem Soc
Chem Commun 1965: 634-5
21
Takahashi K, Nakagawa T.
Studies on constituents of medicinal plants. VIII. The stereochemistry of paulownin
and isopaulownin.
Chem Pharm Bull.
1966;
14
641-7
22
Cantrell C L, Franzblau S G, Fischer N H.
Antimycobacterial plant terpenoids.
Planta Med.
2001;
67
685-94
Prof. Barbara N. Timmermann
Department of Pharmacology and Toxicology
College of Pharmacy
University of Arizona
P.O. Box 210207
1703 E. Mabel Street
Tucson
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USA
Phone: +1-520-626-2481
Fax: +1-520-626-2515
Email: btimmer@pharmacy.arizona.edu