A New Dimeric Dihydrochalcone and a New Prenylated Flavone from the Bud Covers of Artocarpus altilis:  Potent Inhibitors of Cathepsin K

Patil, Ashok D.; Freyer, Alan J.; Killmer, Lewis B.; Offen, Priscilla; Taylor, Paul B.; Votta, Bartholomew J.; Johnson, Randall K.

doi:10.1021/np0105634

Cited by 61 publications

(48 citation statements)

References 10 publications

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“…Several natural products isolated from the bud covers of Artocarpus altilis from Micronesia showed activity in a cathepsin K inhibition assay [190]. Three of the structures are shown in Fig.…”

Section: Cathepsin K Inhibitorsmentioning

confidence: 99%

Thiol Proteases: Inhibitors and Potential Therapeutic Targets

Leung-Toung

Zhao²,

Li³

et al. 2006

CMC

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A better understanding of the biological roles and the pathological consequences of thiol-dependent enzymes has emerged in recent years, and hence considerable progress has been made in identifying and delineating cysteine proteases that can be considered promising drug targets from those involved in housekeeping functions. Cysteine proteases have been implicated in a wide variety of disease processes ranging from cardiovascular, inflammatory, viral and immunological disorders to cancer. The first milestone in drug development of cysteine protease inhibitors has probably been reached, as IDN-6556 (a broad spectrum caspase inhibitor) has recently received Orphan Drug label by the U.S. Food and Drug Administration for use in the treatment of the patients undergoing liver transplantation and other solid organ transplantation. IDN-6556, which blocks apoptosis, is in Phase II human clinical trial in patients undergoing liver transplantation. In addition, more than ten cysteine protease inhibitors are presently at various phases of clinical development/trials for diverse diseases. This review emphasises on the new development from the literature reports since the year 2000 in the exploration of potential cysteine proteases as prospective drug targets, and the investigation of promising inhibitors that can potentially be developed for the treatment of human diseases. Transglutaminases, another class of thiol-dependent enzymes, are not discussed here.

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Section: Cathepsin K Inhibitorsmentioning

confidence: 99%

Thiol Proteases: Inhibitors and Potential Therapeutic Targets

Leung-Toung

Zhao²,

Li³

et al. 2006

CMC

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“…As a result, the structure of sakenin H (8) was concluded as 1-(2,4-dihydroxyphenyl)-3-(7-hydroxy-2-methoxy-2,3-dihydrobenzofuran-4-yl)propan-1-one. The known compounds were identified by analysis of their spectroscopic data and comparison with literature data to be 1- (10) [20], 2-geranyl-2′,3,4,4′-tetrahydroxydihydrochalcone (11) [21], and cycloaltilisin (12) [22]. The isolated compounds were tested for their cytotoxic activity against a PANC-1 human pancreatic cancer cell line in normal DMEM and nutrient-deprived medium (NDM), utilizing an antiausterity strategy.…”

Section: Resultsmentioning

confidence: 99%

Geranyl Dihydrochalcones from Artocarpus altilis and Their Antiausteric Activity

Nguyen

et al. 2014

Planta Med

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Human pancreatic cancer cell lines have remarkable tolerance to nutrition starvation, which enables them to survive under a tumor microenvironment. The search for agents that preferentially inhibit the survival of cancer cells under low nutrient conditions is a novel antiausterity strategy in anticancer drug discovery. In this study, the methanolic extract of the leaves of Artocarpus altilis showed 100 % preferential cytotoxicity against PANC-1 human pancreatic cancer cells under nutrient-deprived conditions at a concentration of 50 µg/mL. Further investigation of this extract led to the isolation of eight new geranylated dihydrochalcones named sakenins A-H (1-8) together with four known compounds (9-12). Among them, sakenins F (6) and H (8) were identified as potent preferentially cytotoxic candidates with PC50 values of 8.0 µM and 11.1 µM, respectively.

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“…Over 130 compounds are identified in various organs of the tree of A. altilis, more than 70 of which derived from the phenylpropanoid pathway, including a number of prenylated dihydrochalcones [16][17][18][19][20][21][22][23][24][25], prenylated flavonoids [21][22][23][25][26][27][28][29][30][31][32], and prenylated aurones [25,33] together with some triterpenoids and phenolic compounds [34][35][36][37] ( Fig. 1-4).…”

Section: Chemical Constituents Of a Altilismentioning

confidence: 99%