Synthesis and in vitro antitumor activity of asperphenamate derivatives as autophagy inducer

Chemical diversity from the Tibetan Plateau fungi Penicillium kongii and P. brasilianum

“…After the semi-preparative reversed-phase HPLC separation step, we isolated 20 compounds ( 1 – 20 ) including 2 new compounds which were named kongiilines A and B ( 1, 7 ) and 2 new natural compounds which were named asperphenamates B and C ( 5, 6 ) (Figures 1 and 2). The two compounds of asperphenamates B and C ( 5, 6 ), as asperphenamate derivatives, were synthesised in 2012 (Yuan et al 2012), but they were isolated from fungi as the natural compounds for the first time.

10.1080/21501203.2017.1331937-F0001Figure 1.The chemical structures of compounds 1–11 from P. kongii.

10.1080/21501203.2017.1331937-F0002Figure 2.The chemical structures of compounds 12–20 from P. brasilianum.

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“…For example, asperphenamate derivatives 1a and 1c , as a pair of isomers, showed activities against T47D, MDA-MB231, and HL60 cell lines, and 1c exhibited the most potent activities against breast cancer cell lines T47D and MDA-MB231 (IC 50  = 8.2 and 11.9 μM, respectively) (Yuan et al 2010). Asperphenamate derivative IM23b, benzyl modified at C15 of asperphenamate, showed the greatest potency in human breast cancer MCF-7 cells (Yuan et al 2012). This compound was also found in P. brevicompactum .…”

Asperphenamate biosynthesis reveals a novel two-module NRPS system to synthesize amino acid esters in fungi

“… 4 1 is a rare linear amino acid ester derived from fungal nonribosomal peptide that exhibits antitumor activity towards a number of cell lines. 5 , 6 It was first isolated from Aspergillus flavipes in 1977 7 and then identified from a wide range of Aspergillus 8 and Penicillium species. 9 , 10 The structure of 1 contains two subunits, N -benzoylphenylalanine ( 2 ) and N -benzoylphenylalaninol ( 3 ), which are connected by an inter-molecular ester bond.…”

Two newPenicilliumspeciesPenicillium buchwaldiiandPenicillium spathulatum, producing the anticancer compound asperphenamate

“…However, asperphenamate has also been found in a series of unrelated plant species: Anaphalis subumbellata (Compositae), Artemisia anomala (Asteraceae), Begonia nantoensis (Begoniaceae), Cantharanthus pusillus (Apocunaceae), Croton hieronymi (Euphorbiaceae), Desmos longiflorus (Annonaceae), Dorstenia dinklagei (Moraceae), Ficus mucoso (Moraceae), Grangea maderaspatana (Compositae), Leucas aspera (Lamiaceae), Medicago polymorpha (Fabaceae), Melastroma malabathricum (Lamiaceae), Miliusa velutina (Annonaceae), Piper aurantiacum (Piperaceae), Piptadenia gonoacantha (Leguminosae), Saurauia napaulensis (Actinidiaceae), Uvaria ufa (Annonaceae), Wikstroemia indica (Thymelaceae) and Zeyhera digitalis (Bignoniaceae) (Battersby & Kapil, 1965;Banerji & Ray, 1981;Wu et al, 2004;Talapatra et al, 1983;Poi & Anityachoudhury, 1986;Jakupovic et al, 1987;Singh & Jain, 1990;Catal an et al, 2003;Bankeu et al, 2010;Geng et al, 2006;Pomini et al, 2006;Sandhu et al, 2006;Vouffo et al, 2008;Xiao et al, 2007;Carvalho et al, 2010;Macabeo et al, 2010;Sirat et al, 2010) leading to the suggestion that asperphenamate may be produced by endophytic fungi rather than plants (Macabeo et al, 2010). Asperphenamate has recently attracted much interest because of its antitumor (Wu et al, 2004;Yuan et al, 2010Yuan et al, , 2012Li et al, 2012) and antimicrobial activity. Furthermore, filamentous fungi are more sustainable and efficient industrial producers of secondary metabolites than the plants, so there is interest in finding further, perhaps more efficient producers of asperphenamate among the fungi.…”