Antifeedant and Cytotoxic Activity of Longipinane Derivatives

Abstract

The polyoxygenated longipinane derivatives 1–8 were tested as antifeedant compounds against the herbivorous insects Spodoptera littoralis, Rhopalosiphum padi, and Myzus persicae. Compounds 1–3 and 8 exhibited significant antifeedant activity against S. littoralis and M. persicae. The antifeedant activity against S. littoralis increased moderately after the C-8 hydroxy group in 3 was removed to afford 1 and increased strongly after the remaining two hydroxy groups were acetylated to afford 2. Compound 1 was active on M. persicae. Compounds 1, 3, and 4, with an unsaturated six-membered ring, exhibited an increase in post-ingestive effects on S. littoralis ranging from antifeedant in the case of 1 to toxic for compounds 3 and 4. These compounds did not have any phytotoxic effect on Lactuca sativa. When tested on a panel of tumoral cells, compounds 2 and 6 exhibited moderate selective cytotoxic effects on the p53 null lung carcinoma cells H1299, which were not affected by the drug paclitaxel. In addition, vibrational circular dichroism (VCD) was applied to the representative longipinene derivative 2 to verify its absolute configuration, and the sensitivity of the VCD methodology was evaluated by comparing spectra of the three diastereoisomers (4R,5S,7R,9R,10R,11R)-7,9-diacetyloxylongipin-2-en-1-one (2), (4R,5S,7S,9R,10R,11R)-7,9-diacetyloxylongipin-2-en-1-one, and (4R,5S,7R,9S,10R,11R)-7,9-diacetyloxylongipin-2-en-1-one.

Key words

Stevia - Asteraceae - longipinane derivatives - antifeedant - cytotoxic - vibrational circular dichroism

References

• 1 Mosetting E, Nes W R. Stevioside. II. The structure of the aglucon.  J Org Chem. 1955;  20 884-889
• 2 Wood H B, Allerton R, Diehl H W, Fletcher H G. Stevioside. I. The structure of the glucose moieties.  J Org Chem. 1955;  20 875-883
• 3 Hernández L R, Catalán C A N, Joseph-Nathan P. The chemistry of the genus Stevia Asteraceae.  Rev Acad Colomb Cienc. 1998;  22 229-279
• 4 Cerda-García-Rojas C M, Pereda R. The phytochemistry of Stevia: a general survey. Kinghorn LD Stevia: The genus Stevia; Medicinal and aromatic plants industrial profiles, Vol. 19, Chapter 5. London; Taylor & Francis 2002: 86-118
• 5 Montiel E, Torres-Valencia J M, Alvarez-García R, Román-Marín L U, Hernández J D, Cerda-García-Rojas C M, Joseph-Nathan P. Structure and conformation of a new longipinene diester from Stevia nepetifolia.  Nat Prod Comm. 2007;  2 525-530
• 6 Joseph-Nathan P, Cerda-García-Rojas C M, Castrejón S, Román L U, Hernández J D. High performance liquid chromatography and nuclear magnetic resonance analysis of longipinene derivatives from Stevia subpubescens var. intermedia.  Phytochem Anal. 1991;  2 77-79
• 7 Román L U, del Río R E, Hernández J D, Joseph-Nathan P, Zabel V, Watson W H. Structure, chemistry, and stereochemistry of rastevione, a sesquiterpenoid from the genus Stevia.  Tetrahedron. 1981;  37 2769-2778
• 8 Román L U, del Río R E, Hernández J D, Cerda-García-Rojas C M, Castañeda R, Joseph-Nathan P. Structural and stereochemistry studies of naturally occurring longipinene derivatives.  J Org Chem. 1985;  50 3965-3972
• 9 Joseph-Nathan P, Cerda-García-Rojas C M, del Río R E, Román-Marín L U, Hernández J D. Conformation and absolute configuration of naturally occurring longipinene derivatives.  J Nat Prod. 1986;  49 1053-1060
• 10 Nafie L A. Vibrational circular dichroism: a new tool for the solution-state determination of the structure and absolute configuration of chiral natural product molecules.  Nat Prod Commun. 2008;  3 451-466
• 11 Burgueño-Tapia E, Joseph-Nathan P. Absolute configuration of eremophilanoids by vibrational circular dichroism.  Phytochemistry. 2008;  69 2251-2256
• 12 Cerda-García-Rojas C M, Catalán C A N, Muro A C, Joseph-Nathan P. Vibrational circular dichroism of africanane and lippifoliane sesquiterpenes from Lippia integrifolia.  J Nat Prod. 2008;  71 967-971
• 13 Rojas-Pérez R E, Cedillo-Portugal E, Joseph-Nathan P, Burgueño-Tapia E. A new longipinene diester from Stevia monardifolia Kunth.  Nat Prod Commun. 2009;  4 757-762
• 14 Burgueño-Tapia E, Castillo L, González-Coloma A, Joseph-Nathan P. Antifeedant and phytotoxic activity of the sesquiterpene p-benzoquinone perezone and some of its derivatives.  J Chem Ecol. 2008;  34 766-771
• 15 Burgueño-Tapia E, González-Coloma A, Castillo L, Joseph-Nathan P. Antifeedant and phytotoxic activity of hydroxyperezone and related molecules.  Z Naturforsch. 2008;  63c 221-225
• 16 Burgueño-Tapia E, González-Coloma A, Martín-Benito D, Joseph-Nathan P. Antifeedant and phytotoxic activity of cacalolides and eremophilanolides.  Z Naturforsch. 2007;  62c 362-366
• 17 Wesarg E, Hoffarth S, Wiewrodt R, Kroll M, Biesterfeld S, Huber C, Schuler M. Targeting BCL-2 family proteins to overcome drug resistance in non-small cell lung cancer.  Int J Cancer. 2007;  121 2387-2394
• 18 Nguyen D M, Chen A, Mixon A, Schrump D S, Roth J A. Sequence-dependent enhancement of paclitaxel toxicity in non-small cell lung cancer by 17-allylamino17-demethoxygeldanamycin.  J Thorac Cardiovasc Surg. 1999;  118 908-915
• 19 Read A P, Strachan T. Cancer genetics. Kingston F Human molecular genetics 2, Chapter 18. New York; Wiley 1999
• 20 Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, Thun M J. Cancer statistics, 2008.  CA Cancer J Clin. 2008;  58 71-96
• 21 Chang G, Guida W C, Still W C. An internal-coordinate Monte Carlo method for searching conformational space.  J Am Chem Soc. 1989;  111 4379-4386
• 22 Perdew J P. Density-functional approximation for the correlation energy of the inhomogeneous electron gas.  Phys Rev B. 1986;  33 8822-8824
• 23 Román L U, Hernández J D, del Río R E, Bucio M A, Cerda-García-Rojas C M, Joseph-Nathan P. Wagner-Meerwein rearrangement of longipinane derivatives.  J Org Chem. 1991;  56 1938-1940
• 24 Poitout S, Bues R. Elevage de plusiereurs espèces de lépidoptères noctuidae sur milieu artificiel riche et sur milieu artificiel simplifié.  Ann Zool Ecol Anim. 1974;  2 79-91
• 25 González-Coloma A, Gutierrez C, Huebner H, Achenbach H, Terrero D, Fraga B M. Selective insect antifeedant and toxic action of ryanoid diterpenes.  J Agric Food Chem. 1999;  47 4419-4424
• 26 Moreno-Osorio L, Cortes M, Armstrong V, Bailén M, González-Coloma A. Antifeedant activity of some polygodial derivatives.  Z Naturforsch. 2008;  63c 215-220
• 27 González-Coloma A, Guadaño A, de Inés C, Martínez-Díaz R, Cortés D. Selective action of acetogenin mitochondrial complex I inhibitors.  Z Naturforsch. 2002;  57c 1028-1034
• 28 Reina M, González-Coloma A, Gutiérrez C, Cabrera R, Rodríguez M L, Fajardo V, Villarroel L. Defensive chemistry of Senecio miser.  J Nat Prod. 2001;  64 6-11
• 29 Moiteiro C, Marcelo-Curto M J, Mohamed N, Bailén M, Martínez-Díaz R, González-Coloma A. Biovalorization of friedelane triterpenes derived from the cork processing industry byproducts.  J Agric Food Chem. 2006;  54 3566-3571