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[Display omitted] • Virtual screening provided 4 candidates potentially able to strongly inhibit COX isoenzymes in inflammatory process. • Compounds (1 – 4) reduced pain in the inflammatory phase response. • Compound 4 inhibited the involvement of PGs in the formation of paw edema. • Compounds 2 and 4 reduced the cellular recruitment of PMN to the inflammatory site. • Compounds 1 , 3 and 4 reduced the neurogenic phase of pain. Inflammation is a natural response of the organism to an infection, trauma, or cellular stress. Pain is the first symptom of acute and chronic inflammation. The standard class of medication to treat inflammatory pain is the nonsteroidal anti-inflammatory drug (NSAID). These drugs are associated with severe side effects such as gastric ulcers, gastritis, or internal bleeding. One of NSAIDs, Dipyrone® (metamizole) is largely used in many European and South American countries despite its dubious effectivity and its withdrawal from the market of several countries. Here, aiming to identify a new anti-inflammatory drug prototype based on Dipyrone® structure, a set of 27 molecules were virtually screened, and 4 compounds containing the active metabolite 4-aminoantipyrine and 1,4-dioxo-2-butenyl fragment were selected for docking, synthesis, and biological evaluation. The selection was based on the number of H-bonds and π- π stacking interactions between the inhibitor and the amino acids within the binding site of the enzyme. Carrageenan-induced paw edema, acetic acid-induced writhing, and formalin assays were used to evaluate inflammation and pain response. The selected compounds 1 – 4 inhibited the involvement of biogenic amines in the formation of paw edema. Compounds 1 – 4 also reduced pain in the inflammatory response phase. It has to be noted that 4-AA may cause agranulocytosis, which should be borne in mind when developing drug candidates of similar structure. Our new drug prototypes based on 4-aminoantipyrine and 1,4-dioxo-2-butenyl moieties open a gate for developing a prototype of nonsteroidal anti-inflammatory drugs. [ABSTRACT FROM AUTHOR]

• Three new carbazole alkaloids were isolated and characterized from Zanthoxylum austrosinense. • The antiproliferative and anti-inflammatory activities of all isolated alkaloids were tested in vitro. • Alkaloids 1 – 12 showed remarkable antiproliferative activities equivalent to that of cisplatin. • Alkaloids 1 – 12 exhibited significant anti-inflammatory effects comparable with that of hydrocortisone. Three new carbazole alkaloids, zanthoaustrones A–C (1 – 3), as well as nine known compounds 4 – 12 , were isolated and characterized from the roots of Zanthoxylum austrosinense Huang (Rutaceae). Their chemical structures were elucidated on the basis of extensive and comprehensive spectroscopic methods, while the known alkaloids were identified by the comparison of their observed spectroscopic data including NMR data, MS data and optical rotation values with the data described in the literature. Furthermore, the antiproliferative activities as well as the anti-inflammatory effects of all isolated alkaloids in vitro were evaluated. All obtained alkaloids 1 – 12 displayed notable antiproliferative activities against diverse human cancer cell lines exhibiting IC 50 values in range of 0.85 ± 0.06 to 29.56 ± 0.17 µM, which is equivalent to the positive control (cisplatin) showing IC 50 values ranging from 1.58 ± 0.09 to 28.69 ± 0.21 µM. Moreover, compounds 1 – 12 exhibited pronounced inhibitory activities on nitric oxide (NO) production with IC 50 values displaying IC 50 values in range of 0.89 ± 0.05 to 9.62 ± 0.15 µM, which is comparable to the positive control (hydrocortisone) holding an IC 50 value of 4.06 ± 0.11 µM. These findings indicate that the separation and characterization of these alkaloids displaying significant antiproliferative activities together with anti-inflammatory effects from the roots of Z. austrosinense could be meaningful to the research and development of new anti-cancer drugs as well as anti-inflammatory agents. [ABSTRACT FROM AUTHOR]

• The chemical constituents from Artocarpus heterophyllus were investigated. • Two new prenylated chromones were isolated from A. heterophyllus. • The antiproliferative and anti-inflammatory effects of 1 – 12 were evaluated in vitro. • 1 – 12 showed significant antiproliferative activities equivalent to cisplatin. • 1 – 12 exhibited remarkable anti-inflammatory effects comparable to hydrocortisone. Two new prenylated chromones, artoheterophines A (1) and B (2), five known prenylated chromones (3 – 7), as well as five known biogenetically related prenylated flavonoids (8 – 12) were isolated and characterized from the stems and leaves of A. heterophyllus. Their chemical structures were unambiguously determined through comprehensive spectral data analyses. The antiproliferative and anti-inflammatory effects of all these isolated prenylated chromones and flavonoids were evaluated in vitro. As a result, compounds 1 – 12 showed notable inhibitory effects against various human cancer cell lines with IC 50 values ranging from 0.36 ± 0.02 to 22.09 ± 0.16 μM. Meanwhile, compounds 1 – 12 exhibited significant inhibitory activities on nitric oxide (NO) production holding IC 50 values in the range of 0.48 ± 0.05–19.87 ± 0.21 µM. These research results suggest that the isolation and characterization of these prenylated chromones (1 – 7) and flavonoids (8 – 12) holding significant antiproliferative and anti-inflammatory activities could be significant to the discovery and development of new natural anti-tumor and anti-inflammatory drugs. The findings also provides a phytochemical evidence for further development and utilization of the stems and leaves of A. heterophyllus in health and pharmaceutical products. [ABSTRACT FROM AUTHOR]

• Eight new serratane triterpenoids were isolated from Lycopodium complanatum. • The absolute configurations of 6 – 8 were determined by DFT GIAO 13C NMR calculations. • The cytotoxic activities were assessed on seven different human cancer cell lines. • All compounds could inhibit the NO release of RAW 264.7 cells induced by LPS. Phytochemical investigation of the ethyl acetate fraction of Lycopodium complanatum led to eight new serratane triterpenoids (lycomplanatums A-H, 1 – 8), along with five known analogues (9 – 13). Their structures were elucidated by extensive spectroscopic methods, including 1D/2D NMR, HRESIMS, and DFT GIAO 13C NMR calculation. Among them, compounds 2 and 13 showed moderate antiproliferative effects against seven human cancer cell lines, especially for MCF-7 with IC 50 values of 13.8–44.7 μM. Additionally, the compounds were screened for anti-inflammatory effects based on their inhibitory activities of nitric oxide (NO) production induced by lipopolysaccharide (LPS) in RAW264.7 cells, and compounds 2 and 13 diminished NO production more potently than others in a concentration-dependent manner. [ABSTRACT FROM AUTHOR]

• The chemical constituents from Clausena lenis were investigated. • Three new prenylated coumarins were isolated from the stems of C. lenis. • The anti-inflammatory effects and anti-HIV activities of all isolated compounds were evaluated in vitro. • Compounds 1 – 12 displayed significant anti-inflammatory effects with the IC 50 values comparable to that of hydrocortisone. • Compounds 1 – 12 exhibited remarkable anti-HIV activities with the EC 50 values in range of 0.17–9.08 µM. The phytochemical study on the stems of Clausena lenis resulted in the isolation of three new prenylated coumarins, clauselenins A–C (1 – 3), together with nine known prenylated coumarins (4 – 12). The chemical structures of new prenylated coumarins (1 – 3) were elucidated by means of comprehensive spectral analyses and the known compounds (4 – 12) were determined by means of comparing their experimental spectral data with those described data in the literatures. All isolated prenylated coumarins were assessed for their anti-inflammatory effects together with anti-HIV activities in vitro. Prenylated coumarins 1 – 12 displayed remarkable inhibitory effects against nitric oxide (NO) production induced by lipopolysaccharide in mouse macrophage RAW 264.7 cells in vitro with the IC 50 values which are comparable to hydrocortisone. Meanwhile, prenylated coumarins 1 – 12 exhibited considerable anti-HIV-1 reverse transcriptase (RT) activities possessing EC 50 values in the range of 0.17–9.08 µM. These findings indicate that the isolation and identification of these prenylated coumarins with pronounced anti-inflammatory effects as well as anti-HIV activities separated from the stems of C. lenis could be of great significance to the development of new anti-inflammatory and anti-HIV agents and their potential applications in the pharmaceutical industry. [ABSTRACT FROM AUTHOR]

• One new jiangrine and two known analogues were isolated from Jiangella alba. • Jiangrines G and A suppressed NO, IL-1β, and IL-6 production. • Pyrrolezanthine suppressed NO and TNF-α expression. • Pro-inflammatory cytokines were mediated by Jiangrines via p38 and NF-κB pathways. Three pyrrol-2-aldehyde derivatives, including one new compound, jiangrine G (JG), two known compounds, jiangrine A (JA), and pyrrolezanthine (PZ), were isolated from the fermentation broth of Jiangella alba associated with a traditional Chinese medicinal plant Maytenus austroyunnanensis. The structure of jiangrine G was elucidated by a detailed spectroscopic data analysis including data from CD spectra. The anti-inflammatory activities assay demonstrated that JG and JA suppressed the production of pro-inflammatory cytokines including NO, IL-1β, and IL-6 as well as inhibited the expression of iNOS in LPS-induced RAW 264.7 cells in a dose-dependent manner. While high concentration of PZ dramatically suppressed the protein expression of TNF-α, but stimulated the release of IL-1β and IL-6. Western blot results revealed that JG, JA, and PZ modulated the expression of pro-inflammatory cytokines via MAPK p38 and NF-κB signaling pathways. For the unique structure of PZ, difference from JG and JA, the signaling pathway involved in mediating its effects on regulating the synthesis of IL-1β and IL-6 are probably more complicated than that of JG and JA. [ABSTRACT FROM AUTHOR]