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Tridepsides from the endophytic fungus colletotrichum gloeosporioides associated with a toxic medicinal plant tylophora ovata
doi: 10.2478/fzm-2021-0006
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Abstract:
Introduction Bioactive secondary metabolites from the microbes living in frigid, toxic or other extreme environments are emerging as a new medicinal resource. Here, we report the discovery of new antidiabetic and anti-inflammatory compounds with novel structures from endophytic fungi hosted toxic medicinal plant. Methods The endophytic fungus isolated from toxic plants was fermented and extracted. The obtained extracts were purified with preparative HPLC to yield pure compounds. The purified compounds were examined by PTP1b inhibition and NO inhibition assays to evaluate their bioactivities. Results One new tridepsides (Compound 1), one new benzeneacetic acid derivative (Compound 3) and five known compounds (Compounds 2 and 4-7) were isolated from the ethyl acetate extract of Colletotrichum gloeosporioides, an endophytic fungus obtained from a toxic medicinal plant Tylophora ovata. Their structures were determined by spectroscopic data (1D and 2D NMR, HRESIMS) analyses. Compound 2 showed significant inhibitory activity against PTP1b with an IC50 value of 0.84 μM. Compounds 2 and 3 exhibited moderate inhibitory activities against the NO (nitric oxide) release in LPS-induced RAW 264.7 cells at 10 μM with percent inhibition of 39% and 33%, respectively. Conclusion The Compound 2 has potent PTP1b inhibitory effect indicating its antidiabetic potential and thus might be considered a lead compound for antidiabetic drug development. -
Key words:
- endophytic fungus /
- toxic medicinal plants /
- tridepsides /
- antidiabetic /
- anti-inflammation
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Table 1. NMR data (600 MHz, methanol-d4) on Compound 1
Position δH (J in Hz) δC δH (J in Hz) δC 1 104.5, C 7' 167.2, C 2 165.0, C 8' 2.13 s 13.1, CH3 3 6.26 d (1.94) 102.0, CH 9' 2.15 s 10.3, CH3 4 164.9, C 10' 2.36 s 16.8, CH3 5 6.35 d (1.94) 113.2, CH 1" 113.2, C 6 145.0, C 2" 165.0, C 7 167.6, C 3" 6.70 d (2.30) 109.0, CH 8 2.65 s 24.8, CH3 4" 155.6, C 1' 134.0, C 5" 6.66 d (2.30) 116.8, CH 2' 127.1, C 6" 144.8, C 3' 150.9, C 7" 170.7, C 4' 123.3, C 8" 2.61 s 23.7, CH3 5' 155.2, C -OCH3 3.86 s 62.8, CH3 6' 127.8, C 
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Table 2. NMR data (600 MHz) of Compound 3 in methanol-d4
Position δHa(J in Hz) δCb 1 173.8, C 2 3.53 s 41.2, CH2 3 126.2, C 4/8 7.08 d, (8.0) 131.3 CH2 5/7 6.74 d, (8.0) 116.3, 6 CH2 157.6, C 1' 169.8, C 2' 156.9, C 3' 5.69 q (1.3) 119.0, 4' 2.14 d (1.3) CH 1" 2.49 ddd (6.4, 6.4, 1.1) 18.6, CH3 2" 40.6, CH2 4.27 t (6.4) 63.2, CH2
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Table 3. The anti-inflammatory activity of Compounds 2 and 3
Compound Anti-inflammatory activity (10 μM) Inhibition rate of NO production (%) Inhibition rate of Cell proliferation (%) 2 39.34% -10.84% 3 33.04% 35.92% DEX (dexamethasone) 99.99% 2.89%
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