Microbial Transformation of Podocarpic Acid and Evaluation of Transformation Products for Antioxidant Activity

Abstract

Podocarpic acid was metabolized by Mucor ramannianus ATCC 9628, and Beauveria bassiana ATCC 7159 to afford two new metabolites, 2α-hydroxy podocarpic acid and 11-hydroxy podocarpic acid, along with the known metabolite 13-hydroxy podocarbic acid. The identity of these metabolites was verified using different spectral methods. The antioxidant activity of the metabolites was tested, and comparable results to those observed for ascorbic acid were obtained.

podocarpic acid - Mucor ramannianus ATCC 9628 - Beauveria bassiana ATCC 7159 - antioxidant

References

• 1 Sherwood R, Short W F. Podocarpic acid I.  J Chem Soc. 1938;  1006-1013
• 2 Brandt C W, Thomas B R. Chemical differentiation of the genera Podocarpus and Dacrydium.  Nature. 1952;  170 1018-1019
• 3 Cambie R C, Cox R E, Sidwell D. Chemistry of the Podocarpaceae. Part LXVII. Phenolic diterpenoids of Podocarpus ferrugineus and other podocarps.  Phytochemistry. 1984;  23 333-336
• 4 Welch S C, Hagan C P. Stereoselective total synthesis of podocarpic acid.  Synth Commun. 1973;  3 29-32
• 5 Kanjilal P R, Alam S K, Ghatak U R. An improved total synthesis of podocarpic acid by a cycloalkylation route.  Synth Commun. 1981;  11 795-802
• 6 Manabu N, Jiang H X, Hideko N, Kaoru F. General entry to the synthesis of optically active diterpenoids of C-20β series.  Tetrahedron Lett. 1989;  30 4141-4144
• 7 Banerjee A K, Acevedo J C, Canudas-Gonzalez N. The utility of podocarpic acid in the synthesis of naturally occurring terpenes.  Bull Soc Chim Belg. 1990;  99 9-28
• 8 Davis B R, Watkins W B. Chemistry of podocarpacea-XV: elaboration of podocarpic acid.  Tetrahedron. 1968;  24 2165
• 9 He W, Gavai A, Huang F C, Regan J, Hanney B, Poli G, Bruno J, Chan W K, Djuric S W, Yu K T, Zilberstein A. Novel cytokine release inhibitors. Part IV: analogs of podocarpic acid.  Bioorg Med Chem Lett. 1999;  9 469-474
• 10 Lam T, Ling T, Chowdhury C, Chao T, Bahjat F R, Lloyd G K, Moldawer L L, Palladino M A, Theodorakis E A. Synthesis of a novel family of diterpenes and their evaluation as anti-inflammatory agents.  Bioorg Med Chem Lett. 2003;  13 3217-3221
• 11 Jayasuriya H, Herath K B, Ondeyka J G, Guan Z, Borris R P, Tiwari S, De Jong W, Chavez F, Moss J, Stevenson D W, Beck H T, Slattery M, Zamora N, Schulman M, Ali A, Sharma N, MacNaul K, Hayes N, Menke J G, Singh S B. Diterpenoid, steroid, and triterpenoid agonists of liver X receptors from diversified terrestrial plants and marine sources.  J Nat Prod. 2005;  68 1247-1252
• 12 Liu W, Chen S, Dropinski J, Colwell L, Robins M, Szymonifka M, Hayes N, Sharma N, MacNaul K, Hernandez M, Burton C, Sparrow C P, Menke J G, Singh S B. Design, synthesis, and structure-activity relationship of podocarpic acid amides as liver X receptor agonists for potential treatment of atherosclerosis.  Bioorg Med Chem Lett. 2005;  15 4574-4578
• 13 Singh S B, Ondeyka J G, Liu W, Chen S, Chen T S, Li X, Bouffard A, Dropinski J, Jones A B, McCormick S, Hayes N, Wang J, Sharma N, MacNaul K, Hernandez M, Chao Y, Baffic J, Lam M, Burton C, Sparrow C P, Menke J G. Discovery and development of dimeric podocarpic acid leads as potent agonists of liver X receptor with HDL cholesterol raising activity in mice and hamsters.  Bioorg Med Chem Lett. 2005;  15 2824-2828
• 14 Bennett D J, Carswell E L, Cooke A J, Edwards A S, Nimz O. Design, structure activity relationships and X-ray co-crystallography of non-steroidal LXR agonists.  Curr Med Chem. 2008;  15 195-209
• 15 Staschke K A, Hatch S D, Tang J C, Hornback W J, Munroe J E, Colacino J M, Muesing M A. Inhibition of influenza virus hemagglutinin-mediated membrane fusion by a compound related to podocarpic acid.  Virology. 1998;  248 264-274
• 16 Parish E J, Miles D H. Investigation of the antitumor activity of podocarpic acid derivatives.  J Pharm Sci. 1984;  73 694-696
• 17 Bauch J, Schmidt O, Hillis W E, Yazaki Y. Deposits in the heartshakes of Dacrydium species and their toxicity against fungi and bacteria.  Holzforschung. 1977;  31 1-7
• 18 Parish E J, Bradford S, Geisler V J, Hanners P K, Heupel R C, Le P H, Nes W D. Synthesis and fungistatic activity of podocarpic acid derivatives.  ACS Symp Ser. 1987;  325 140-149
• 19 Zamora J M, Mora E C, Parish E J. A comparison of the cytotoxicity of nordihydroguaiaretic acid and its derivatives.  J Tenn Acad Sci. 1992;  67 77-80
• 20 Soederberg T A, Johansson A, Gref R. Toxic effects of some conifer resin acids and tea tree oil on human epithelial and fibroblast cells.  Toxicology. 1996;  107 99-109
• 21 Hill J A, Johnson A W, King T J. Synthesis of podocarpane-6,7-diol, a degradation product of maytenone.  J Chem Soc. 1961;  4430-4433
• 22 El Sayed K A, Hamann M T, Waddling C A, Jensen C, Lee S K, Dunstan C A, Pezzuto J M. Structurally novel bioconversion products of the marine natural product sarcophine effectively inhibit JB6 cell transformation.  J Org Chem. 1998;  63 7449-7455
• 23 Re R, Pellegrini N, Proteggente A, Pannala A, Yang M, Rice-Evans C. Antioxidant activity applying an improved ABTS radical cation decolorization assay.  Free Radic Biol Med. 1999;  26 1231-1237