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
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.
4
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