MICROBIAL METABOLISM OF AN ANTI-HIV AND ANTI-MALARIAL NATURAL PRODUCT ANDROGRAPHOLIDE
Keywords:
Microbial transformation, Andrographolide, Anti-HIV, Andrographis paniculataAbstract
Objective: Andrographolide (1), the main crystalline bitter principle of Andrographis paniculata nees. (also known as rice bitter in the West Indies) was first isolated by Gorter, and characterized as trihydroxy lactone. It was also isolated from Holmskilodia sanguinea in very good yield. It possesses a wide range of biological activities, which is also important in the therapeutic fields including anti-inflammatory, anti-malarial, anti-viral, immuno-stimulant, anti-HIV, and cardiovascular properties. In the present study, we first time studied the microbial metabolism of andrographolide (1) with Cunninghamella elegans (TSY 0865) and Cephalosporium aphidicola (IMI-68689).
Methods: Microbial cultures of the C. elegans and C. aphidicola were grown on Potato dextrose agar (PDA) at 25°C and stored at 4°C. Medium for C. aphidicola was prepared by mixing Glucose (50.0 g), KH2PO4 (1.0 g), MgSO4.7H2O (2.0 g), Glycin (2.0 g), KCl (1.0 g) and Gibberella trace element solution (2.0 mL) into distilled water (1 L) and maintained pH at 5.6. While C. elegans medium was prepared by adding Glucose (10.0 g), peptone (5.0 g), KH2PO4 (5.0 g), yeast extract (5.0 g), NaCl (5.0 g) and glycerol (10 mL) into distilled water (1 L) and maintained pH at 5.6.
Results: Two compounds were obtained as transformed products. Based on physical and spectroscopic data, these have been identified as andropanolide (2) and 14-deoxy-11,12-didehydro andrographolide (3). Both compounds were previously obtained by the phytochemical investigation of A. paniculata and biotransformed product as well.
Conclusion: It could be concluded that C. elegans and C. aphidicola were able to produce oxidative derivatives of 1 in a regio- and stereoselective manner. Present investigation has been conducted for the first time with C. elegans and C. aphidicola. Incubation of 1 for 9 days with fungal strains yielded isomerized and oxidative products 2 and 3. Structures of all metabolites were elucidated by using spectroscopic techniques.
Downloads
References
Uttekar MM, Das T, Pawar RS, Bhandari B, Menon V, Nutan Bhat SV. Anti-HIV activity of semisynthetic derivatives of andrographolide and computational study of HIV-1 gp120 protein binding. Eur J Med Chem 2012;56:368–74.
Wang B, Li J, Huang WL, Zhang HB, Qian H, Zheng YT. Synthesis and biological evaluation of andrographolide derivatives as potent anti-HIV agents. Chinese Chem Lett 2011;22:781–4.
Arifullah M, Namsa ND, Mandal M, Chiruvella KK, Vikrama P, Gopal GR, et al. Evaluation of anti-bacterial and anti-oxidant potential of andrographolide and echiodinin isolated from callus culture of Andrographis paniculata Nees. Asian Pac J Trop Biomed 2013;3(8):604–10.
Aromdee C, Sriubolmas N, Wiyakrutta S, Suebsasna S, Khunkitti W. Effect of the derivatives of andrographolide on the morphology of Bacillus subtilis. Arch Pharmcal Res 2011;34(1):71–7.
Murugan K, Selvanayaki K, Al-Sohaibani S. Antibiofilm activity of Andrographis paniculata against cystic fibrosis clinical isolate Pseudomonas aeruginosa. World J Microb Biot 2010;27(7):1661–68.
Sharifuddin Y, Parry EM, Parry JM. The genotoxicity and cytotoxicity assessments of andrographolide in vitro. Food Chem Toxicol 2012;50(5):1393–8.
Sirion U, Kasemsook S, Suksen K, Piyachaturawat P, Suksamrarn A, Saeeng R. New substituted C-19-andrographolide analogues with potent cytotoxic activities. Bioorg Med Chem Lett 2012;22(1):49–52.
Singha PK, Roy S, Dey S. Protective activity of andrographolide and arabinogalactan proteins from Andrographis paniculata Nees. against ethanol-induced toxicity in mice. J Ethnopharmacol 2007;111(1):13–21.
Chang KT, Lii CK, Tsai CW, Yang AJ, Chen HW. Modulation of the expression of the pi class of glutathione S-transferase by Andrographis paniculata extracts and andrographolide. Food Chem Toxicol 2008;46(3):1079–88.
Hidalgo MA, Hancke JL, Bertoglio JC, Burgos RA. Andrographolide a new potential drug for the long term treatment of rheumatoid arthritis disease. Innovative Rheumatol 2013;1:246-70.
Deng S, Zhang BJ, Wang CY, Tian Y, Yao JH, An L, et al. Microbial transformation of deoxyandrographolide and their inhibitory activity on LPS-induced NO production in RAW 264.7 macrophages. Bioorg Med Chem Lett 2012;22(4):1615–8.
Sultan S, Zaimi M, Anouar EH, Shah SAA, Salim F, Rahim R, et al. Absolute configuration of 20β-hydroxyprednisolone, a biotransformed product of an Anti-Inflammatory drug predinisolone by marine endophytic fungus Penicilium lapidosum. Mol 2014;19(9):13775-87.
Choudhary MI, Atif M, Shah SAA, Sultan S, Erum S, Khan SN, et al. Biotransformation of dehydroabietic acid with microbial cell cultures and α-glucosidase inhibitory activity of resulting metabolites. Int J Pharm Pharm Sci 2014;6:375-8.
Sultan S, Choudhary MI, Khan SN, Fatima U, Atif M, et al. Fungal transformation of cedryl acetate and α-glucosidase inhibition assay, quantum mechanical calculations and molecular docking studies of its metabolites. Eur J Med Chem 2013;62:764–70.
Choudhary MI, Sultan S, Jalil S, Anjum S, Rahman AA, Fun HK. Microbial transformation of mesterolone. Chem Biodivers 2005;2:392-400.
Choudhary MI, Sultan S, Khan MTH, Atta-ur-Rahman. Microbial transformation of 17α-ethynyl-and 17α-ethylsteroids, and tyrosinase inhibitory activity of transformed products. Steroids 2005;70(12):798-802.
Choudhary MI, Sultan S, Yaqoob M, Musharraf SG, Yasin A, Shaheen F, et al. Microbial transformation of cortisol and prolyl endopeptidase inhibitory activity of its transformed products. Nat Prod Res 2003;17:389-95.
Choudhary MI, Sultan S, Hassan Khan MT, Yasin A, Shaheen F, Atta-ur-Rahman. Biotransformation of (+)-androst-4-ene-3, 17-dione. Nat Prod Res 2004;18(6):529-35.
Musharraf SG, Atta-ur-Rahman, Choudhary MI, Sultan S. Microbial transformation of (+)-adrenosterone. Nat Prod Lett 2002;16(5):345-9.
Sultan S, Ghani NA, Shah SAA, Ismail NH, Noor MZ, Naz H. Microbial transformation of anthraquinones-A Review. Biosci Biotechnol Res Asia 2013;10(2):577-82.
Shah SAA, Sultan S, Zaimi M. Biotransformation of tissue-specific hormone tibolone with fungal culture Trichothecium roseum. J Mol Struct 2013;1042:118-22.
Shah SAA, Sultan S, Adnan HS. A whole-cell biocatalysis application of steroidal drugs. Orient J Chem 2013;29(2):389-403.
Shah SAA, Sultan S, Adnan HS. Solid phase microbial transformation of cortexolone and prolyl endopeptidase inhibitory activity of the transformed products. Int J Pharm Pharm Sci 2011;3 Suppl 1: 1-6.
Casañola-MartÃn GM, Marrero-Ponce Y, Khan MTH, Ather A, Sultan S, Torrens F, et al. TOMOCOMD-CARDD descriptors-based virtual screening of tyrosinase inhibitors: evaluation of different classification model combinations using bond-based linear indices. Bioorg Med Chem 2007;15(3):1483-503.
Shah SAA, Tan HL, Sultan S, Faridz MABM, Shah MABM, Nurfazilah S, et al. Microbial-catalyzed biotransformation of multifunctional triterpenoids derived from phytonutrients. Int J Mol Sci 2014;15(7):12027-60.
Shah SAA, Sultan S, Hassan NB, Muhammad FKB, Faridz MABM, HussainFBM, et al. Biotransformation of 17α-ethynyl substituted steroidal drugs with microbial and plant cell cultures: a review. Steroids 2013;78(14):1312-24.
Azam SS, Reaz Uddin, Shah SAA, Zaheer-ul-Haq. Molecular docking studies of potent inhibitors of tyrosinase and ï¡-glucosidase. Med Chem Res 2012;21(8):1677-83.
Choudhary MI, Shah SAA, Atta-ur-Rahman, Khan SN, Khan MTH. Alpha-glucosidase and tyrosinase inhibitors from fungal hydroxylation of tibolone. Steroids 2010;75(12):956-66.
Choudhary MI Shah SAA, Atta-ur-Rahman. Microbial transformation of anabolic steroids. Nat Prod Res 2008;22(15):1289–96.
Choudhary MI, Batool I, Shah SAA, Khan SN, Atta-ur-Rahman. Microbial transformation of oleanolic acid by Fusarium lini and ï¡-glucosidase inhibitory activity of its transformed products. Nat Prod Res 2008;22(6):489-94.
Atta-ur-Rahman, Choudhary MI, Basha FZ, Abbas G, Khan SN, Shah SAA. Science at the interface of chemistry and biology: Discoveries of α-glucosidase inhibitors and antiglycation agents. Pure Appl Chem 2007;79(12):2263-8.
Choudhary MI, Yousuf S, Samreen, Shah SAA, Ahmed S, Atta-ur-Rahman. Biotransformation of physalin h and antileishmanial activity of transformed product. Chem Pharm Bull 2006;54(7):927-30.
Choudhary MI, Shah SAA, Sami A, Ajaz A, Shaheen F, Atta-ur-Rahman. Fungal metabolites of E-Guggulsterone and their antibacterial and antioxidant activities. Chem Biodivers 2005;2:516-24.
Choudhary MI, Batool I, Shah SAA, Nawaz SA, Atta-ur-Rahman. Microbial hydroxylation of pregnenolone derivative and cholinesterase inhibitory activity. Chem Pharma Bull 2005;53;1455-9.
Choudhary MI, Shah SAA, Musharraf SG, Shaheen F, Atta-ur-Rahman. Microbial trabsformation of dehydroepiandrosterone. Nat Prod Res 2003;17(3):215-20.
He X, Wang Y, Hu H, Wu Y, Zeng X. Novel bioconversion products of andrographolide by Aspergillus ochraceus and their cytotoxic activities against human tumor cell lines. J Mol Catal B Enzym 2011;68(1):89–93.
He X, Zeng X, Hu H, Wu Y. Cytotoxic biotransformed products from andrographolide by Rhizopus stolonifer ATCC 12939. J Mol Catal B Enzym 2010;62(3-4):242–7.
Matsuda T, Kuroyanagi M, Sugiyama S, Umehara K, Ueno A, Nishi K. Cell differentiation-inducing diterpenoids from Andrographis paniculata Nees. Chem Pharm Bull 1994;42(6):1216-25.
Pramanick S, Banerjee S, Achari B, Das B, Sibabrata AKS, Mukhopadhayay S, Neuman A, et al. Andropanolide and Isoandrographolide, Minor Diterpenoids from Andrographis paniculata: Structure and X-ray Crytallography Analysis. J Nat Prod 2006;69(3):403-5.