Identification of a New Uncompetitive Inhibitor of Adenosine Deaminase from Endophyte Aspergillus niger sp.

Abstract

Adenosine deaminase (ADA) is an enzyme widely distributed from bacteria to humans. ADA is known as a potential therapeutic target for the treatment of lymphoproliferative disorders and cancer. Endophytes are endosymbionts, often bacteria or fungi, which live within plant tissues and internal organs or intercellular space. Endophytes have a broad variety of bioactive metabolites that are used for the identification of novel natural compounds. Here, 54 morphologically distinct endophyte strains were isolated from six plants such as Peganum harmala Linn., Rheum officinale Baill., Gentiana macrophylla Pall., Radix stephaniae tetrandrae, Myrrha, and Equisetum hyemale Linn. The isolated strains were used for the search of ADA inhibitors that resulted in the identification of the strain with the highest inhibition activity, Aspergillus niger sp. Four compounds were isolated from this strain using three-step chromatography procedure, and compound 2 was determined as the compound with the highest inhibition activity of ADA. Based on the results of H andC NMR spectroscopies, compound 2 was identified as 3-(4-nitrophenyl)-5-phenyl isoxazole. We showed that compound 2 was a new uncompetitive inhibitor of ADA with high cytotoxic effect on HepG2 and SMCC-7721 cells (the IC values were 0.347 and 0.380 mM, respectively). These results suggest that endophyte strains serve as promising sources for the identification of ADA inhibitors, and compound 2 could be an effective drug in the cancer treatment.

Putative Anticancer Compounds from Plant-Derived Endophytic Fungi: A Review

“…Fusarithioamide B, a new type benzamide, isolated form Fusarium c ., showed potent activity against several cell lines [ 160 ]. 3-(4-nitrophenyl)-5-phenyl isoxazole was reported to have a potent effect against HepG2 and SMCC-7721 cells [ 161 ], while spiciferone F was reported to have a strong effect against MCF7 [ 162 ]. Liu et al isolated two metabolies, namely xylariphthalide A and cis -4-hydroxy-6-deoxytalone, and Sharma V. et al isolated Xylarolide A from Diaporthe spp.…”

Therapeutic Perspectives of Adenosine Deaminase Inhibition in Cardiovascular Diseases

“…In contrast, neutral sapo(ge)nins and phytosterols did not affect ADA activity [ 74 , 96 ]. Recently, Zhang et al isolated endophytes from six plants, which are widely used in Chinese herbal medicine for the screening of ADA inhibitors [ 75 ]. They identified a strong uncompetitive inhibitor of ADA activity, 3-(4-nitrophenyl)-5-phenylisoxazole, which demonstrated an IC 50 value equal to 0.380 mM.…”

Equisetum extracts are anti-inflammatory and antibacterial, an oral potential therapeutic agent

“…Equisteum can also be toxic, depending on the dose, due to its alkaloid content [34][35] . It has compounds that can affect the action of Adenosine deaminase [36] . In conjunction with silver nanoparticles it presents strong toxic effect against HepG2 cell lines [26] .…”