MICROBIAL METABOLISM OF AN ANTI-HIV AND ANTI-MALARIAL NATURAL PRODUCT ANDROGRAPHOLIDE

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), KH 2 PO 4 (1.0 g), MgSO 4 .7H 2 O (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), KH 2 PO 4 (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.