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C16H12O3, monoclinic, P21/c (no. 14), a = 10.9636(14) Å, b = 12.1767(12) Å, c = 10.1557(13) Å, β = 116.588(16)°, V = 1212.4(3) Å3, Z = 4, Rgt (F) = 0.0366, wR ref(F 2) = 0.1019, T = 250.00(10) K.

C23H34O5, orthorhombic, P212121 (no. 19), a = 11.1838(3) Å, b = 11.7824(3) Å, c = 16.3160(5) Å, V = 2149.99(10) Å3, Z = 4, Rgt ${R}_{\mathrm{g}\mathrm{t}}$ (F) = 0.0399, wRref $w{R}_{\mathrm{r}\mathrm{e}\mathrm{f}}$ (F 2) = 0.1097, T = 293 K.

C11H12BrNO2, monoclinic, P21/n (no. 14), a = 7.5143(12) Å, b = 11.8968(15) Å, c = 12.9852(13) Å, β = 105.575(14)°, V = 1118.2(3) Å3, Z = 4, R gt(F) = 0.0607, wR ref(F 2) = 0.1615, T = 293.00(10) K.

Two series of 1,4-naphthoquinone-chromone hybrids 4a (4aa–4ao) and 4b (4ba–4bq) were designed, synthesized and evaluated as antitumor agents. Most of the compounds exhibited moderate to excellent cytotoxicity to tumor cells (K562 and A549), especially the 4a series compounds that showed equal or stronger antiproliferative activity compared to positive control cisplatin on two different types of cells (except for 4al and 4an). Among them, compound 4ac showed significant inhibitory activity on A549 cells with an IC50 value of 2.93 μM, and was 5.2 times more active than cisplatin (IC50 = 15.32 ± 2.64 μM). Meanwhile, AO/EB staining, flow cytometry, cell morphology, and ultrastructural analysis revealed that compound 4ac could induce A549 cell apoptosis and arrest at the G1 phase. Further mechanism studies speculated that compound 4ac may regulate the p53-MDM2 pathway, alter the Bax/Bcl-2 ratio to release Cyt c, activate the mitochondrial apoptosis pathway to induce cell apoptosis, and inhibit A549 cell proliferation through cycle arrest. Collectively, compound 4ac could be used as a potential candidate compound for anti-lung cancer drugs. [ABSTRACT FROM AUTHOR]

This study focuses on the synthesis of novel vinpocetine derivatives (2–25) and their biological evaluation. The chemical structures of the synthesized compounds were fully characterized using techniques such as 1H NMR, 13C NMR, and HRMS. The inhibitory activity of the synthesized compounds on PDE1A was evaluated, and the results revealed that compounds 3, 4, 5, 12, 14, 21, and 25 exhibited superior inhibitory activity compared to vinpocetine. Compound 4, with a para-methylphenyl substitution, showed a 5-fold improvement in inhibitory activity with an IC50 value of 3.53 ± 0.25 μM. Additionally, compound 25, with 3-chlorothiazole substitution, displayed an 8-fold increase in inhibitory activity compared to vinpocetine (IC50 = 2.08 ± 0.16 μM). Molecular docking studies were conducted to understand the binding models of compounds 4 and 25 within the active site of PDE1A. The molecular docking study revealed additional binding interactions, such as π–π stacking and hydrogen bonding, contributing to the enhanced inhibitory activity and stability of the ligand–protein complexes. Overall, the synthesized vinpocetine derivatives demonstrated promising inhibitory activity on PDE1A, and the molecular docking studies provided insights into their binding modes, supporting further development of these compounds as potential candidates for drug research and development. [ABSTRACT FROM AUTHOR]

Potentilla kleiniana Wight et Arn（PK, 'Wu Pi Feng' in Chinese） was recorded as Miao ethnic medicine for treatment of fever, cough, ulcer, and erysipelas for thousands years. This study aimed to evaluate the antiviral activity of four PK extracts and seven compounds by using HIV-1 protease (HIV-1 PR). In addition, Ultra-High Performance Liquid Chromatography and High Resolution Mass Spectrometry (UPLC-HRMS) was employed to identify the bioactive components. The toxicity assessment of the extracts was done before antiviral screening using a highly specific human aspartyl protease, renin protease by fluorimetric method. As a result, seven compounds and four extracts of PK inhibited HIV-1 PR with IC50 range from 0.009 to 0.36 mg/mL, and did not appreciably inhibit the general human protease renin. This study first demonstrated that four PK extracts, ellagic acid and ursolic acid potent inhibit HIV-1 protease, could be used as an efficacious drug candidate to treat SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

A series of novel derivatives of 18β-glycyrrhetinic acid (GA) were synthesized by introducing aromatic or heterocyclic structures to extend the side chain, thereby enhancing their interaction with amino acid residues in the active pocket of the target protein. These compounds were structurally characterized using 1H NMR, 13C NMR, and HRMS. The compounds were subsequently evaluated for their inhibitory effects on HIV-1 protease and cell viability in the human cancer cell lines K562 and HeLa and the mouse cancer cell line CT26. Towards HIV-1 protease, compounds 28 and 32, which featured the introduction of heterocyclic moieties at the C3 position of GA, exhibited the highest inhibition, with inhibition rates of 76% and 70.5%, respectively, at 1 mg/mL concentration. Further molecular docking suggests that a 3-substituted polar moiety would be likely to enhance the inhibitory activity against HIV-1 protease. As for the anti-proliferative activities of the GA derivatives, incorporation of a thiazole heterocycle at the C3- position in compound 29 significantly enhanced the effect against K562 cells with an IC50 value of 8.86 ± 0.93 µM. The introduction of electron-withdrawing substituents on the C3-substituted phenyl ring augmented the anti-proliferative activity against Hela and CT26 cells. Compound 13 exhibited the highest inhibitory activity against Hela cells with an IC50 value of 9.89 ± 0.86 µM, whereas compound 7 exerted the strongest inhibition against CT26 cells with an IC50 value of 4.54 ± 0.37 µM. These findings suggest that further modification of GA is a promising path for developing potent novel anti-HIV and anticancer therapeutics. [ABSTRACT FROM AUTHOR]

Scutellaria barbata D. Don (SB, Chinese: Ban Zhi Lian), a well-known medicinal plant used in traditional Chinese medicine, is rich in flavonoids. It possesses antitumor, anti-inflammatory, and antiviral activities. In this study, we evaluated the inhibitory activities of SB extracts and its active components against HIV-1 protease (HIV-1 PR) and SARS-CoV2 viral cathepsin L protease (Cat L PR). UPLC/HRMS was used to identify and quantify the major active flavonoids in different SB extracts, and fluorescence resonance energy transfer (FRET) assays were used to determine HIV-1 PR and Cat L PR inhibitions and identify structure–activity relationships. Molecular docking was also performed, to explore the diversification in bonding patterns of the active flavonoids upon binding to the two PRs. Three SB extracts (SBW, SB30, and SB60) and nine flavonoids inhibited HIV-1 PR with an IC50 range from 0.006 to 0.83 mg/mL. Six of the flavonoids showed 10~37.6% inhibition of Cat L PR at a concentration of 0.1 mg/mL. The results showed that the introduction of the 4′-hydroxyl and 6-hydroxyl/methoxy groups was essential in the 5,6,7-trihydroxyl and 5,7,4′-trihydroxyl flavones, respectively, to enhance their dual anti-PR activities. Hence, the 5,6,7,4′-tetrahydroxyl flavone scutellarein (HIV-1 PR, IC50 = 0.068 mg/mL; Cat L PR, IC50 = 0.43 mg/mL) may serve as a lead compound to develop more effective dual protease inhibitors. The 5,7,3′,4′-tetrahydroxyl flavone luteolin also showed a potent and selective inhibition of HIV-1 PR (IC50 = 0.039 mg/mL). [ABSTRACT FROM AUTHOR]

C23H34O5, orthorhombic, P212121 (no. 19), a = 11.1838(3) Å, b = 11.7824(3) Å, c = 16.3160(5) Å, V = 2149.99(10) Å3, Z = 4, R g t (F) = 0.0399, w R r e f (F2) = 0.1097, T = 293 K. [ABSTRACT FROM AUTHOR]

C16H12O3, monoclinic, P21/c (no. 14), a = 10.9636(14) Å, b = 12.1767(12) Å, c = 10.1557(13) Å, β = 116.588(16)°, V = 1212.4(3) Å3, Z = 4, Rgt(F) = 0.0366, wRref(F2) = 0.1019, T = 250.00(10) K. [ABSTRACT FROM AUTHOR]

C11H12BrNO2, monoclinic, P21/n (no. 14), a = 7.5143(12) Å, b = 11.8968(15) Å, c = 12.9852(13) Å, β = 105.575(14)°, V = 1118.2(3) Å3, Z = 4, Rgt(F) = 0.0607, wRref(F2) = 0.1615, T = 293.00(10) K. [ABSTRACT FROM AUTHOR]

The exploration of new catalytic properties of the known functionalities would facilitate the exploitation of new ligands and/or organocatalysts that are able to achieve reactivity and selectivity unattainable by known ones. In this context, carbonyl‐stabilized phosphorus ylides have emerged as a type of novel ligand motifs and organocatalysts, exhibiting versatile catalytic activity towards some important organic reactions such as cross‐couplings, cyanation, CO2 fixation. This Minireview summarizes these recent advances, highlights the advantages and limitations, and outlines synthetic opportunities still open for further investigation. [ABSTRACT FROM AUTHOR]

The first allylic alkylation of difluoroenoxysilanes with MBH carbonates catalyzed by triethylenediamine (DABCO) is developed, which allows rapid access to multifunctional α‐gem‐difluoroketones with up to 97% yields. Moreover, the gram‐scale synthesis and the diversifying transformation of products to valuable gem‐difluorinated molecules highlight the practicality of this methodology. [ABSTRACT FROM AUTHOR]

A novel chiral phosphoric acid catalyst bearing two acidic phenolic hydroxyl groups was synthesized. Its as a chiral Brøsted acid has been examined in the Friedel-Crafts and enones as a model reaction. In comparison with the other chiral phosphoric acid catalysts, the reaction catalyzed by the novel chiral catalyst afforded the desired 3-substituted indoles in a higher (up to 69% ee). [ABSTRACT FROM AUTHOR]

A mild and efficient method for the construction of pyrrolidinyl spirooxindoles via a 1,3-dipolar cycloaddition reaction of (E)-N-Boc-3-alkylidene-indolin-2(3H)ones with azomethine ylides has been established. The presence of anN-Boc group in the indolin-2(3H)ones obviously increased the activity and stereoselectivity of the reaction, affording the desired pyrrolidinyl spirooxindoles4with up to 85% yield and up to >99/1drvalue. Furthermore, the antibacterial activity of these compounds againstStaphylococcus aureus(ATCC-25825) has been tested at minimum concentration, and some of them exhibit moderate antibacterial activity. [Supplementary materials are available for this article. Go to the publisher's online edition ofSynthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.] [ABSTRACT FROM AUTHOR]

C11H12BrNO2, monoclinic, P21/n (no. 14), a = 7.5143(12) Å, b = 11.8968(15) Å, c = 12.9852(13) Å, β = 105.575(14)°, V = 1118.2(3) Å3, Z = 4, Rgt(F) = 0.0607, wRref(F2) = 0.1615, T = 293.00(10) K. [ABSTRACT FROM AUTHOR]

C23H34O5, orthorhombic, P212121 (no. 19), a = 11.1838(3) Å, b = 11.7824(3) Å, c = 16.3160(5) Å, V = 2149.99(10) Å3, Z = 4, R g t (F) = 0.0399, w R r e f (F2) = 0.1097, T = 293 K. [ABSTRACT FROM AUTHOR]

C16H12O3, monoclinic, P21/c (no. 14), a = 10.9636(14) Å, b = 12.1767(12) Å, c = 10.1557(13) Å, β = 116.588(16)°, V = 1212.4(3) Å3, Z = 4, Rgt(F) = 0.0366, wRref(F2) = 0.1019, T = 250.00(10) K. [ABSTRACT FROM AUTHOR]

This study aims to investigate the role and mechanism of Gusong Qianggu Decoction(GSQG) in attenuating bone loss in ovariectomized mice by targeting the endoplasmic reticulum stress(ERS)-induced apoptosis of osteocytes. After the modeling of osteoporosis in mice with bilateral ovary removal(OVX), 60 mice were randomized by the random number method into six groups: sham,model, low-, medium-, and high-dose GSQG(GSQG-L, GSQG-M, and GSQG-H, respectively), and estradiol(E_2), with 10 mice in each group. The mice in each group were administrated with corresponding drugs by gavage one month after surgery and the administration lasted for 3 months. Enzyme-linked immunosorbent assay(ELISA) was employed to determine the serum levels of osteocalcin(OCN), procollagen type Ⅰ N-terminal propeptide(PINP), carboxy-terminal cross-linked telopeptide of type Ⅰ collagen(CTX),and anti-tartarte acid phosphatase 5b(TRAcP-5b). Micro-CT was employed to observe the changes in bone microstructure of the distal femur. Hematoxylin-eosin(HE) staining was employed to observe the morphology of the bone tissue. RT-qPCR was conducted to determine the m RNA levels of tibial stem osteogenesis-associated genes [type Ⅰ collagen(Col-Ⅰ), alkaline phosphatase(ALP), Runtrelated transcription factor-2(Runx2), bone sialoprotein(BSP), and OCN] and bone-breaking related genes [tartrate-resistant acid phosphatase(TRAP), nuclear factor-activated T cell 1(NFATc1), and cathepsin K(CATK)]. TUNEL staining and immunohistochemistry were employed to detect the apoptosis of osteoblasts. Western blot was employed to measure the expression of ERS-related proteins glucose-regulated protein 78( Grp78), protein kinase RNA-like endoplasmic reticulum kinase( PERK), phosphorylated PERK(p-PERK),eukaryotic translation initiation factor 2 alpha(eIF2α), phosphorylated e IF2α(p-eIF2α), inositol-requiring enzyme 1 alpha(IRE1α), phosphorylated IRE1α(p-IRE1α), and activating transcription factor 6(ATF6) in the proximal tibial bone tissue. The results showed that GSQG significantly recovered the levels of OCN, PINP, TRAc P-5b, and CTX in the serum of ovariectomized mice, and Micro-CT showed that GSQG improved the bone microstructure of distal femur in a dose-dependent manner. Compared with the model group, GSQG widened and increased the bone trabeculae, restored the reticular structure with neat arrangement and enlarged interstitial gaps, and reduced the number of TUNEL-positive cells(P<0. 05, P<0. 01). Furthermore, GSQG down-regulated the expression levels of cysteine aspartate protease-3( caspase-3) and factor Bcl-2-associated X protein( Bax)(P< 0. 05,P<0. 01) and up-regulated the expression level of Bcl-2(P<0. 05, P<0. 01). The GSQG groups showed up-regulated m RNA levels of Col-Ⅰ, ALP, Runx2, BSP, and OCN(P< 0. 01) and down-regulated m RNA levels of TRAP, NFATc1, and CATK(P< 0. 05,P<0. 01). In addition, GSQG, especially GSQG-H, down-regulated the protein levels of Grp78, p-PERK, p-eIF2, p-IRE1α, and ATF6(P< 0. 05, P< 0. 01). In conclusion, GSQG can inhibit the apoptosis of osteocytes by inhibiting the Grp78/PERK/e IF2α/IRE1α/ATF6 signaling pathway in the proximal tibia tissue, thus reducing bone loss in ovariectomized mice.

This study focuses on the synthesis of novel vinpocetine derivatives ( 2 - 25 ) and their biological evaluation. The chemical structures of the synthesized compounds were fully characterized using techniques such as 1 H NMR, 13 C NMR, and HRMS. The inhibitory activity of the synthesized compounds on PDE1A was evaluated, and the results revealed that compounds 3 , 4 , 5 , 12 , 14 , 21 , and 25 exhibited superior inhibitory activity compared to vinpocetine. Compound 4 , with a para-methylphenyl substitution, showed a 5-fold improvement in inhibitory activity with an IC 50 value of 3.53 ± 0.25 μM. Additionally, compound 25 , with 3-chlorothiazole substitution, displayed an 8-fold increase in inhibitory activity compared to vinpocetine (IC 50 = 2.08 ± 0.16 μM). Molecular docking studies were conducted to understand the binding models of compounds 4 and 25 within the active site of PDE1A. The molecular docking study revealed additional binding interactions, such as π-π stacking and hydrogen bonding, contributing to the enhanced inhibitory activity and stability of the ligand-protein complexes. Overall, the synthesized vinpocetine derivatives demonstrated promising inhibitory activity on PDE1A, and the molecular docking studies provided insights into their binding modes, supporting further development of these compounds as potential candidates for drug research and development.