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[Display omitted] • Four types of novel heterocyclic derivatives (a total of 31 compounds) as glycogen phosphorylase (GP) inhibitors were designed, synthesized and evaluated. • The structure–activity relationship (SAR) of synthesized compounds was demonstrated. • Compound IIIh showed strong inhibitory activity against both RMGP (IC 50 = 0.21 ± 0.03 µM) and HBGP (IC 50 = 0.09 ± 0.002 µM). • Compound IIIh as a potential glycogen phosphorylase inhibitor has beneficial effect on cardioprotective. The purpose of this study was to evaluate the effect of GP inhibitor as a potential pharmaceutical target on MI/R injury. Four different structural types of novel compounds (I, II, III, and IV) were designed and synthesized, obtaining 31 novel GP inhibitors. SAR studies revealed that the conjugates of 5-chloroindole with benzo six-membered heterocyclic were found to elevate the activity. In particular, compound IIIh (IC 50 = 0.21 ± 0.03 µM) emerged as a potent derivative against RMGPa, being approximately 2-fold less potent than that of PSN-357. In order to screen out a compound for in vivo activity test, we further conducted an experiment of inhibition against three different subtypes of GPa (HLGPa, HMGPa and HBGPa) and the corresponding affinity experiment. As a result, compound IIIh showed strong inhibitory activity against the above three subtypes of GP, especially on HBGPa (IC 50 = 0.09 ± 0.002 µM), which was relatively close to that of positive control ingliforib (IC 50 = 0.16 ± 0.02 µM). The affinity of compound IIIh to HBGPa was 4.3 times higher than that of HLGPa, and 1.1 times higher than that of HMGPa. This fact further proved that compound IIIh has a higher inhibitory effect on HMGPa than the other two subtypes. Besides, in vivo activity evaluation demonstrated that compound IIIh exhibited obviously cardioprotective effect on MI/R injury mice. The discovery of compound IIIh provides a new strategy for developing novel GP inhibitors with myocardial ischemia protection. [ABSTRACT FROM AUTHOR]

[Display omitted] • Ten new polypropionate derivatives, decempyrones A–J (1 – 10) were isolated from Fusarium graminearum. • Absolute configurations were fixed by JBCA, chemical degradation, geminal proton rule, and modified Mosher's method. • Decempyrones C and J exhibited potent anti-inflammatory activity. • Decempyrones C and J also displayed MptpA kinase inhibitory activity. Under guidance of 1H NMR, ten new polypropionate derivatives, decempyrones A–J (1 – 10) along with two known analogues (11 and 12), were isolated from the marine-derived fungus Fusarium decemcellulare SYSU-MS6716. The planar structures were elucidated on the basis of extensive spectroscopic analyses (1D and 2D NMR, and HR-ESIMS). The absolute configuration of the chiral centers in the side chain is a major obstacle for the structure identification of natural polypropionate derivatives. Herein, the J -based configurational analysis (JBCA), chemical degradation, geminal proton rule, and the modified Mosher's method were adopted to fix their absolute configurations in the side chain. Compounds 3 and 10 exhibited potent anti-inflammatory activity by inhibiting the production of NO in RAW264.7 cells activated by lipopolysaccharide with IC 50 values 22.4 ± 1.8 and 21.7 ± 1.1 μM. In addition, compounds 3 and 10 displayed MptpA inhibitory activity with an IC 50 value of 19.2 ± 0.9 and 33.1 ± 2.9 µM. Structure-activity relationships of the polypropionate derivatives were discussed. [ABSTRACT FROM AUTHOR]

• Four new polyketides were isolated from a coral-derived fungus Penicillium sclerotiorin. • Five isolated compounds exhibited significant anti-inflammatory activities by inhibiting NO production. • The possible anti-inflammatory mechanism was downregulating the expression of iNOS and COX-2 at mRNA level. • Binding interactions with iNOS were predicted. Four new polyketides, including an unusual naphthoquinone derivative (1), two azaphilone analogous (2 , 7) and an α -pyrone (12), were isolated from the gorgonian-derived fungus Penicillium sclerotiorum CHNSCLM-0013 together with nine known compounds. Their structures were identified based on the 1D, 2D NMR, HRESIMS, single crystal X-ray diffraction and the absolute configurations were determined by comparing the 1H NMR chemical shift and optical rotations with those reported in literature. In the bioassay, compounds 2 , 6 , 7 , 10 and 12 exhibited significant inhibitory activities against the nitric oxide (NO) production in the LPS-induced macrophage RAW 264.7 with the IC 50 values in the range of 2.5–18.0 μM. Compounds 2 , 6 and 7 exhibited the possible mechanism of downregulating the expression of iNOS and COX-2 in mRNA level. The primary structure-activity relationship was also discussed based on the molecular-modeling. This study will make a contribution to the chemical diversities of polyketides especially the azaphilone derivatives and the discovery of potential anti-inflammatory agent from marine fungi. [ABSTRACT FROM AUTHOR]