In this paper the cytotoxicity of mycelium and broth constituents of endophytic fungus Aspergillus nidulans from Nyctanthes arbor-tristis is reported for the first time. The study shows that fungus Aspergillus nidulans from Nyctanthes arbor-tristis is capable of producing biologically active natural compounds and provides a scientific rationale for further chemical investigations into endophyte-producing natural products.

Endophytic fungi are a substantial source of bioactive secondary metabolites. Present studies on Aspergillus nidulans―an endophytic fungus from Nyctanthes arbor-tristis Linn. afforded one new 1, 5-dihydroxy-3-methylxanthone-6-carboxylic acid methyl ester (1) and one known 5, 10-dihydro-phenazine-1-carboxylic acid (2) compound. The structures were elucidated by spectral techniques (Mass, 1D and 2D NMR), and their urease, carbonic anhydrase and prolyl endopeptidase inhibitory activities were evaluated. Compound 1 showed notable prolyl endopeptidase inhibition (IC50 = 3.13 ± 0.09 µM) and compound 2 showed significant carbonic anhydrase (IC50 =14.3 ± 1.05 µM) and urease (IC50 = 24.3 ± 1.15 µM) inhibition.

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 1H and 13C NMR and MS. The inhibitory effect of isolated compounds was evaluated on urease and carbonic anhydrase (bCA II) enzymes in vitro. Compounds 3 and 6 showed significant urease inhibition (IC50 19 and 21 µM), while other compounds exhibited varying degrees of urease inhibition (IC50 33 – 51 µM). Compounds 4, 6 and 7 exhibited significant inhibition of bCA II (IC50 values 21, 25 and 18 µM respectively), compounds 1–3 displayed moderate inhibition (IC50 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.

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