Depsitinuside: a new depside galactoside from an endophytic fungus isolated from<i>Viburnum tinus</i>

Nazir, Mamona; Sultan, Misbah; Riaz, Naheed; Hafeez, Maria; Hussain, Hidayat; Ahmed, Ishtiaq; Schulz, Barbara; Draeger, Siegfried; Jabbar, Abdul; Krohn, Karsten; Ashraf, Muhammad; Saleem, Muhammad

doi:10.1080/10286020.2011.606811

Cited by 3 publications

(2 citation statements)

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“…Depsides are most often found in lichens, 23,24) but have also been isolated from high plants 25,26) and marine or endophytic fungi. 27,28) Nordivaricatic acid (1), divarinyl divarate (2), and trivaric acid (3) were all originally isolated from lichens. [17][18][19] In the present study, the three depsides, for the first time, are isolated from a soil derived fungal strain.…”

Section: Resultsmentioning

confidence: 99%

Trivaric Acid, a Potent Depside Human Leukocyte Elastase Inhibitor

Zheng¹,

Zhang

Lu³

et al. 2012

Biological & Pharmaceutical Bulletin

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Human leukocyte elastase (HLE) is a serine protease implicated in several inflammatory diseases, and represents a major target for anti-inflammatory drug development. In the present study, nordivaricatic acid (1), divarinyl divarate (2), and trivaric acid (3), three depsides isolated from the culture of a soil derived fungal strain were identified as inhibitors of HLE. Two didepsides 1 and 2 showed low inhibitory activity. In contrast, trivaric acid, a para-tridepside, exhibited highly potent inhibitory activity with an IC 50 value of 1.8 µM and a K i of 0.6 µM. Kinetic investigations with trivaric acid showed that this inhibition is reversible, competitive pattern. Further studies on the selectivity of three depsides toward serine proteases showed that they did not inhibit chymotrypsin, trypsin and thrombin even at 150 µM.Key words human leukocyte elastase; depside; trivaric acid; fungus Human leukocyte elastase (HLE, EC 3.4.21.37), also known as human neutrophil elastase (HNE) and human granulocyte elastase, is a member of the chymotrypsin superfamily of serine proteases, and highly expressed in the azurophilic granules of polymorphonuclear leukocytes (PMNLs). HLE can very efficiently degrade tissue matrix proteins such as elastin, collagen, fibronectin, laminin and proteoglycan by activating procollagenase, prostromelysin, and progelatinase, and is potentially one of the most destructive enzymes in the body. 1)Under physiological conditions, HLE is released from PMNLs because of inflammatory stimuli and mediators, and is inactivated by a number of endogenous proteinase inhibitors such as α 2 -antiplasmin, α 1 -antichymotrypsin, antithrombin, and tissue inhibitor of metalloproteinases.2,3) The imbalance between HLE and its endogenous inhibitors leads to abnormal tissue destruction which is associated with a number of inflammatory diseases including pulmonary emphysema, 4) adult respiratory distress syndrome (ARDS), 5) chronic bronchitis, 6) chronic obstructive pulmonary disease (COPD), 7,8) rheumatoid arthritis (RA), 9) and acute lung injury (ALI). 10) In addition, HLE plays an important role in invasion and metastasis of human breast and lung cancer.11) Hence, HLE has been an important therapeutic target.Research and development of potent small molecular HLE inhibitors has been conducted for over three decades worldwide, and a number of synthetic and natural inhibitors have been discovered and evaluated biologically both in vitro and in vivo.12,13) The most advanced synthetic inhibitor is ONO-5046 (sivelestat) which has been launched in Japan (2002) as an injectable formulation for the treatment of acute lung injury associated with systemic inflammatory response syndrome, ARDS and ALI.14,15) MR-889 (midesteine), an irreversible HNE inhibitor, is also in pre-registration for the treatment of COPD in Italy. 16) In our searching for novel HLE inhbitors from natural or synthetic compounds, three depsides from the culture of a soil derived fungal strain were identified as inhibitors of HLE. Fungal Strain and Ferme...

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Section: Resultsmentioning

confidence: 99%

Trivaric Acid, a Potent Depside Human Leukocyte Elastase Inhibitor

Zheng¹,

Zhang

Lu³

et al. 2012

Biological & Pharmaceutical Bulletin

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show abstract

“…The final conference lecture was given by Prof. Karsten Krohn (University of Paderborn), who summarized the history for many of his discoveries of new bioactive fungal metabolites that demonstrated the structure and activity diversity and drug potential of this source for finding new bioactive natural products. 15,16 The evenings during the conference were pleasantly filled by a walking tour and dinner in Potsdam and a boat tour and on-board dinner on the Spree River.…”

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confidence: 99%