Urease and Carbonic Anhydrase Inhibitory Effect of Xanthones from Aspergillus nidulans , an Endophytic Fungus of Nyctanthes arbor-tristis

Abstract Urease plays a major role in the pathogenesis of peptic and gastric ulcer and also causes acute pyelonephritis and development of infection-induced reactive arthritis. Carbonic anhydrases (CA) cause pathological disorders such as epilepsy (CA I), glaucoma, gastritis, renal, pancreatic carcinomas, and malignant brain tumors (CA II). Although various synthetic urease and carbonic anhydrase inhibitors are known, these have many side effects. Hence, present studies were undertaken on ethyl acetate extract of Aspergillus nidulans , an endophytic fungus separated from the leaves of Nyctanthes arbor-tristis Linn. and led to the isolation of five furanoxanthones, sterigmatin ( 1 ), sterigmatocystin ( 3 ), dihydrosterigmatocystin ( 4 ), oxisterigmatocystin C ( 5 ), acyl-hemiacetal sterigmatocystin ( 6 ), and a pyranoxanthone ( 2 ). Acetylation of 3 gave compound O -acetyl sterigmatocystin ( 7 ). Their chemical structures were elucidated by 1 H and 13 C NMR and MS. The inhibitory effect of isolated compounds was evaluated on urease and carbonic anhydrase ( b CA II) enzymes in vitro. Compounds 3 and 6 showed significant urease inhibition (IC 50 19 and 21 µM), while other compounds exhibited varying degrees of urease inhibition (IC 50 33 – 51 µM). Compounds 4, 6 and 7 exhibited significant inhibition of b CA II (IC 50 values 21, 25 and 18 µM respectively), compounds 1 – 3 displayed moderate inhibition (IC 50 61, 76 and 31 µM respectively) while 5 showed no inhibition. A mechanistic study of the most active urease inhibitors was also performed using enzyme kinetics and molecular docking. All compounds were found non-toxic on the NIH-3T3 cell line.