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Planta Med 2023; 89(04): 377-384
DOI: 10.1055/a-1908-0935
Biological and Pharmacological Activity
Original Papers

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

Talea Sana
1   H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan
,
Majid Khan
1   H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan
,
Almas Jabeen
2   Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan
,
Sidrah Shams
2   Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan
,
Taibi Ben Hadda
3   Laboratoire de Chimie des Matériaux, Faculté des Sciences, Université Mohammed Premier, Oujda, Morocco
,
Sabira Begum
1   H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan
,
Bina Shaheen Siddiqui
1   H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan
› Author AffiliationsSupported by: Pakistan Academy of Sciences 5-9/PAS/52
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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 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.

Key words

Nyctanthes arbor-tristis - Oleaceae - Aspergillus nidulans - urease - carbonic anhydrase - inhibitory effect

Supporting Information

    1H- and 13C-NMR data of compounds 1–7, and 1H-NMR spectra of compounds 1–7 are provided as Supporting Information.

  • Supporting Information


Publication History

Received: 01 April 2022

Accepted after revision: 12 July 2022

Article published online:
10 January 2023

© 2022. Thieme. All rights reserved.

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