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[Display omitted] • D-π-A fluorescent probes were reasonably designed and developed through systematic changes in electron-donor and-acceptor groups. • Probes M−H−SO 3 with a hydrophilic sulfonate group displayed sufficient selectivity for discrimination of HSA from BSA. • Probe M−H−SO 3 can bind to the IB site of HSA, yielding a substantial fluorescent enhancement. • The probe M−H−SO 3 can be used for detecting human serum albumin in urine samples. HSA (human serum albumin), a most abundant protein in blood serum, plays a key role in maintaining human health. Abnormal HSA level is correlated with many diseases, and thus has been used as an essential biomarker for therapeutic monitoring and biomedical diagnosis. Development of small-molecule fluorescent probes allowing the selective and sensitive recognition of HSA in in vitro and in vivo is of fundamental importance in basic biological research as well as medical diagnosis. Herein, we reported a series of new synthesized fluorescent dyes containing D-π-A constitution, which exhibited different optical properties in solution and solid state. Among them, dye M−H−SO 3 with a hydrophilic sulfonate group at electron-acceptor part displayed selectivity for discrimination of HSA from BSA and other enzymes. Upon binding of dye M−H−SO 3 with HSA, a significant fluorescence enhancement with a turn-on ratio about 96-fold was triggered. The detection limit was estimated to be ∼ 40 nM. Studies on the interaction mechanism revealed that dye M−H−SO 3 could bind to site III of HSA with a 1:1 binding stoichiometry. Furthermore, dye M−H−SO 3 has been applied to determine HSA in real urine samples with good recoveries, which provided a useful method for HSA analysis in biological fluids. [ABSTRACT FROM AUTHOR]

[Display omitted] • Apigenin analogs (L1–L27) were designed and synthesized. • The synthetic molecules were screened for α-glucosidase inhibitory activities. • Compound L22 was found to be the most active compound. • L22 presented in vivo hypoglycemic activity in STZ-induced diabetic mice. This study investigated the inhibitory potential of a series of synthesized compounds (L1-L27) on α-glucosidase. Among them, compound L22 showed significant inhibitory effect. Through enzymatic kinetics studies, we demonstrated that L22 acts via a non-competitive inhibition mode with a K i value of 2.61 μM, highlighting its high affinity for the enzyme. Molecular docking studies revealed the formation of hydrogen bonds between L22 and α-glucosidase and diverse interactions with neighboring amino acid residues. Furthermore, molecular dynamics simulations confirmed the stability of the L22-α-glucosidase complex. In a mouse model of type 2 diabetes, treatment with L22 significantly lowered fasting blood glucose levels, and reduced insulin resistance, suggesting its potential as a therapeutic agent for type 2 diabetes. Furthermore, L22 showed a protective effect against oxidative stress in the liver and alleviated liver and pancreatic abnormalities. These results provide valuable insights into the mechanism of action of L22 and its potential applications to treat type 2 diabetes, and improve liver health. [ABSTRACT FROM AUTHOR]

[Display omitted] • Two enantiomeric pairs of acylphloroglucinols were isolated from Syzygium szemaoense. • They possess a macrocyclic system with an unprecedented carbon skeleton. • A new biogenetically related long-chain acylphloroglucinol was also obtained. • Some of the isolates showed inhibitory effects on ACLY and DRAK2. Two enantiomeric pairs of macrocyclic acylphloroglucinols (1a / 1b and 2a / 2b) with an unprecedented carbon skeleton featuring a bicyclo[12.3.1]octadecane core, together with an undescribed biogenetically related long-chain acylphloroglucinol (3), were isolated from Syzygium szemaoense. Their structures were fully established by spectroscopic method, X-ray crystallographic analysis, and ECD calculation. Compounds 1b and 2a / 2b exhibited inhibition against death-associated protein kinase-related apoptosis inducing protein kinase 2 (DRAK2) and ATP citrate lyase (ACLY), respectively. [ABSTRACT FROM AUTHOR]

[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] • Four undescribed seco -polyprenylated acylphloroglucinols from H. elodeoides. • A possible biosynthetic pathway of 1 – 4 from normal PAPs was proposed. • Compound 1 induced MCF-7 cell apoptosis. • Compound 1 arrested cell cycle at S phase via inducing oxidative DNA damage. Four undescribed seco -polyprenylated acylphloroglucinols (seco -PAPs), elodeoidesones A-D (1 – 4), were characterized from Hypericum elodeoides. Compound 1 represents the 1,6- seco -PAPs with fascinating 5/5 fused ring, while 2 – 4 possess a 1,2- seco -PAPs skeleton with a five-membered lactone core. Their structures including absolute configurations were established by spectroscopic analyses and quantum chemical computations. A possible biosynthetic pathway of 1 – 4 from normal PAPs was proposed. All the isolates were investigated for their cytotoxicity against tumor cells. Notably, 1 inhibited the proliferation of MCF-7 cells with the IC 50 value of 7.34 μM. Mechanism investigation indicated that 1 induced MCF-7 cells apoptosis by blocking cell cycle at S phase via inducing oxidative DNA damage. [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]