Search

Abstract: A series of 5,6-dihydroxypyrimidine analogs were synthesized and evaluated for their anti-HIV activity in vitro. Among all of the analogs, several compounds exhibited significant anti-HIV activity, especially 1b and 1e, which showed the most potent anti-HIV activity with EC50 values of 0.14 and 0.15μM, and TI (therapeutic index) values of >300 and >900, respectively. Further docking studies revealed that the representative compounds 1e and 3a could meet the HIV-1 integrase inhibition minimal requirements of a chelating domain (two metal ions) and an aromatic domain (π–π stacking interactions). [Copyright &y& Elsevier]

Abstract: Seven previously unreported daphnane-type diterpene esters named acutilobins A–G, together with 12 known ones, were isolated from EtOAc extract of Daphne acutiloba Rehd. Their structures were elucidated based on the spectroscopic data. The cytotoxic and anti-HIV-1 activities of these daphnane-type diterpene esters were evaluated through bioassays. Fourteen of these isolates exhibited definite cytotoxic activities against the five human tumor cell lines HL-60, SMMC-7721, A-549, MCF-7, and SW480. Additionally, anti-HIV-1 activities were observed in 13 daphnane-type diterpene esters, among which acutilobins A–G exhibited significant anti-HIV-1 activities with EC50 below 1.5nM and SI over 10,000. Particularly, genkwanineVIII showed the strongest activity with EC50 0.17nM and SI 187,010. [Copyright &y& Elsevier]

The combination of photodynamic therapy (PDT) and chemotherapy is a prospective strategy to improve antitumor efficacy. Herein, a series of novel cytotoxic chlorin-based derivatives as dual photosensitizers (PSs) and histone deacetylase inhibitors (HDACIs) were synthesized and investigated for biological activity. Among them, compound 15e showed definite HDAC2 and 10 inhibitory activities by up-regulating expression of acetyl-H4 and highest phototoxicity and dark-toxicity, which was more phototoxic than Talaporfin as a PS while with stronger dark-toxicity compared to vorinostat (SAHA) as a HDACI. The biological assays demonstrated that 15e was liable to enter A549 cells and localized in mitochondria, lysosomes, golgi and endoplasmic reticulum (ER) etc. multiple organelles, resulting in higher cell apoptosis rate and ROS production compared to Talaporfin. Moreover, it could induce tumor cell autophagy as a dual PS and HDACI. All results suggested that compound 15e could be applied as a potential dual cytotoxic drug for PDT and chemotherapy. [Display omitted] • The dual-mode cytotoxic chlorin-based derivatives as PSs and HDACIs were synthesized. • HDAC inhibitory activities of target compounds were investigated. • Photo-cytotoxicity and dark-cytotoxicity for target compounds were evaluated. • Compound 15e exhibited the strongest PDT and chemotherapy efficacies. • Dual-mode cytotoxic mechanism of compound 15e was further studied. [ABSTRACT FROM AUTHOR]

Nine undescribed limonoids, 18(13 → 14)- abeo -15β,21-dihydroxy-24,25,26,27-tetranor-3,7-dioxoapotirucalla-1,9(11),13(17),20(22)-tetraen-23,21-olide (Toonaone A), 21-hydroxy-24,25,26,27-tetranor-3,7,15-trioxoapotirucalla-1,9(11),20(22)-trien-23,21-olide (Toonaone B), 7α,21-dihydroxy-12α-isobutyryl-24,25,26,27-tetranor-3,15-dioxoapotirucalla-1,20(22)-dien-23,21-olide (Toonaone C), 7,8- seco -7-methyl ester-11β-acetoxy-14β,15β-epoxy-21-hydroxy-24,25,26,27-tetranor-3-oxoapotirucalla-1,8(30),20(22)-trien-23,21-olide (Toonaone D), 7,8- seco -7-methyl ester-11β-acetoxy-14β,15β-epoxy-23-hydroxy-24,25,26,27-tetranor-3-oxoapotirucalla-1,8(30),20(22)-trien-21,23-olide (Toonaone E), 7,8- seco -7-methyl ester-11β-acetoxy-14β,15β-epoxy-6β,21-dihydroxy-24,25,26,27-tetranor-3-oxoapotirucalla-1,8(30),20(22)-trien-23,21-olide (Toonaone F), 7,8- seco -7-methyl ester-14β,15β-epoxy-8α,21-dihydroxy-24,25,26,27-tetranor-3-oxoapotirucalla-1,20(22)-dien-23,21-olide (Toonaone G), 7,8- seco -7-methyl ester-14β,15β-epoxy-6β,8α,21-trihydroxy-24,25,26,27-tetranor-3-oxoapotirucalla-1,20(22)-dien-23,21-olide (Toonaone H), 7,8- seco -7-methyl ester-14β,15β-epoxy-6β,8α,21-trihydroxy-24,25,26,27-tetranor-3-oxoapotirucalla-1,20(22)-dien-21,23-diimide (Toonaone I), and five known analogues were isolated from the twigs of Toona ciliata M. Roem. (Meliaceae). Toonaone A possesses the first rare 18(13 → 14)- abeo -limonoid skeleton reported from the genus Toona. Their structures were elucidated using spectroscopic data analyses and quantum chemistry calculations. Biological evaluation showed that toonaone C, toonaone D, toonaone G, toonaciliatavarin F, and toonaciliatavarin G exhibited significant anti-NLRP3 inflammasome activity with IC 50 values ranging from 3.74 to 18.7 μM. GMDMD, IL-1β, and caspase-1 analyses suggested that toonaone D inhibited NLRP3 inflammasome activation and blocked macrophage pyroptosis. [Display omitted] • Nine undescribed limonoids and five analogues were isolated from of Toona ciliate. • Toonaone A possesses a rare 18(13. → 14)-abeo-limonoid skeleton. • Spectroscopic analyses and quantum chemistry calculations were used to elucidate structures. • Some compounds could significantly inhibit NLRP3 inflammasome activation. [ABSTRACT FROM AUTHOR]

This study aimed to improve the biological effectiveness and pharmacokinetic properties of chlorin e 6 , a second-generation photosensitizer (PS), for tumor photodynamic therapy (PDT). Herein, the novel 31-hexyloxy chlorin e 6 -based 152- or 131-amino acid derivatives 3a , 3b , 3c and 8 were synthesized and their photophysical properties and in vitro bioactivities such as phototoxicity against A549, HeLa and melanoma B16–F10 cells, reactive oxygen species (ROS) production and subcellular localization were evaluated. In addition, preferred target compounds were also investigated for their in vivo pharmacokinetic in SD rats and in vivo antitumor efficacies in C57BL/6 mice bearing melanoma B16–F10 cells. Apparently, simultaneous introduction of amino acid residue and n -hexyloxy chain in chlorin e 6 made a significant improvement in photophysical properties, ROS production, in vitro and in vivo PDT efficacy. Encouragingly, all target compounds showed higher in vitro phototoxicity than Talaporfin, and that 3c (152-Lys) exhibited strongest phototoxicity and highest dark toxicity/phototoxicity ratio, followed by 8 (131-Asp), 3a (152-Asp) and 3b (152-Glu). Moreover, in vivo PDT antitumor efficacy of 3a , 3c and 8 was all better than that of Talaporfin, and that both 3c and 8 had stronger PDT antitumor efficiency than 3a. The overall results suggested that these novel 31-hexyloxy chlorin e 6 -based 152- or 131-amino acid derivatives, especially 3c and 8 , might be potential antitumor candidate drugs for clinical treatment of melanoma by PDT. Image 1 • The 31-hexyloxy chlorin e 6 -based 152- or 131-amino acid derivatives were synthesized. • In vitro photodynamic activity and mechanism of target compounds were investigated. • In vivo antitumor potency and pharmacokinetic of target compounds were evaluated. • In vitro and in vivo PDT antitumor efficacy of 3a , 3c , 8 were better than Talaporfin. • In vitro and in vivo PDT antitumor efficacy of 3c and 8 were superior to 3a. [ABSTRACT FROM AUTHOR]

Leonurus japonicus (motherwort) has been widely used to treat gynecological disorders, in which estrogen is often dysregulated, for a long time in China and other Asian countries. However, the chemical constituents and mechanisms underlying the activity of this medicinal plant are not fully understood. Seventeen of forty-six tested natural products from L. japonicus showed stimulatory or inhibitory effects on estrogen biosynthesis with different potency in human ovarian granulosa-like KGN cells. Luteolin-7-methylether (XLY29) potently inhibited 17β-estradiol production (IC 50 : 5.213 μM) by decreasing the expression of aromatase, the only enzyme in vertebrates that catalyzes the biosynthesis of estrogens, but had no effect on the catalytic activity of aromatase. XLY29 decreased the expression of aromatase promoter I.3/II, and suppressed the phosphorylation of cAMP response element-binding protein. XLY29 potently inhibited phosphorylation of p38 mitogen-activated protein kinase and AKT but had no effect on phosphorylation of extracellular signal-regulated kinase and c-Jun N-terminal kinase. XLY29 also decreased the serum 17β-estradiol level and disturbed estrous cycle in mice. These results suggest that modulation of estrogen biosynthesis is a novel effect of L. japonicus , and XLY29 warrants further investigation as a new therapeutic means for the treatment of estrogen-related diseases. [ABSTRACT FROM AUTHOR]

Since tyrosine kinase inhibitor (TKI) could reverse ABCG2-mediated drug-resistance, novel chlorin e 6 -based conjugates of Dasatinib and Imatinib as photosensitizer (PS) were designed and synthesized. The results demonstrated that conjugate 10b showed strongest phototoxicity against HepG2 and B16-F10 cells, which was more phototoxic than chlorin e 6 and Talaporfin. It could reduce efflux of intracellular PS by inhibiting ABCG2 in HepG2 cells, and localize in mitochondria, lysosomes, golgi and ER, resulting in higher cell apoptosis rate and ROS production than Talaporfin. Moreover, it could induce cell autophagy and block cell cycle in S phase, and significantly inhibit tumor growth and prolong survival time on BALB/c nude mice bearing HepG2 xenograft tumor to a greater extent than chlorin e 6. Consequently, compound 10b could be applied as a promising candidate PS due to its good water-solubility and stability, low drug-resistance, high quantum yield of 1O 2 and excellent antitumor efficacy in vitro and in vivo. [Display omitted] • The conjugates of chlorin e 6 with Dasatinib or Imatinib were synthesized. • In vitro PDT antitumor activities of all target compounds were investigated. • In vivo antitumor potency and mechanism of preferred compound 10b were evaluated. • In vitro PDT antitumor efficacy of 10b was better than chlorin e 6 and talaporfin. • In vivo PDT antitumor efficacy of 10b was superior to chlorin e 6. [ABSTRACT FROM AUTHOR]

Fourteen undescribed seco -type diterpenoids, named nudifloids A-N, together with ten known analogs, were isolated from the leaves of Callicarpa nudiflora. Nudifloids A-N had a characteristic 3,4- seco -labdane-type diterpenoid skeleton, whereas nudifloids A-C and K–N were 3,4- seco -norditerpenoids. Nudifloid A was the first example of a 3,4- seco -12,13,14,15,16-quartnor-labdane diterpenoid, with a seven-membered lactone ring formed through esterification between C-3 and C-11. Nudifloids B and C were a pair of highly modified 3,4- seco -labdane nor-diterpenoid epimers, of which C-2 and C-18 were cyclized together to form a cyclohexene fragment. The structures of these undescribed diterpenoids were established by spectroscopic analysis and reference data. The anti-inflammatory activity of diterpenoids in rich yield was evaluated by analyzing the inhibition of lipopolysaccharide plus nigericin-induced pyroptosis in J774A.1 cells. Nudifloids D and E exhibited prominent anti-NLRP3 inflammasome activity, with IC 50 values of 1.80 and 1.59 μM, respectively. Cell permeability assays revealed that nudifloid D inhibited pyroptosis, which could ameliorate inflammation by blocking the activation of the NLRP3 inflammasome. Guiding by anti-inflammatory activity, fourteen undescribed 3,4- seco -labdane diterpenoids were isolated from the leaves of Callicarpa nudiflora , and evaluated the anti-inflammatory activity of abundant diterpenoids. [Display omitted] • Bioassay-guided isolation of C. nudiflora to obtain twenty-four seco -diterpenoids. • Of which, fourteen undescribed 3,4- seco -labdane diterpenoids were determined. • Nudifloid A exhibits the first example with a seven-numbered lactone ring. • Nudifloids D and E exhibited prominent inflammatory inhibitory activity. [ABSTRACT FROM AUTHOR]

Ethyl acetate fraction of Toddalia asiatica was fractionated to yield fifteen previously undescribed prenylated coumarins, asiaticasics A-O (1 – 15) along with nine (16 – 24) known derivatives. The structures of these undescribed coumarins were established by spectroscopic analysis and reference data. Biological activity evaluation showed that compound 3 with the IC 50 value of 2.830 μM and compound 12 with the IC 50 value of 0.682 μM owned anti-inflammatory activity by detecting the rate of lactate dehydrogenase release in pyroptosis J774A.1 cells. The results showed that the expression of Caspase-1 and IL-1 β was decreased in a dose-dependent manner in the compound 12 treatment group, suggesting that compound 12 may reduce pyroptosis by inhibiting NLRP3 inflammasome. To further determine that compound 12 treatment can inhibit macrophage pyroptosis, morphological observation was performed and the results were consistent with the bioactivity evaluation. [Display omitted] • Twenty-four coumarins were isolated from the ethyl acetate fraction of Toddalia asiatica. • Fifteen coumarins that have not been described before. • Two undescribed compounds showed low IC 50 values and could exert effective anti-inflammatory effects. • Compound 12 inhibited pyroptosis in a dose-dependent manner. [ABSTRACT FROM AUTHOR]

Vitex negundo var. Cannabifolia (Sieb. et Zucc.) Hand.-Mazz. leaves and twigs were used to isolate a new phenyldihydronaphthalene-type lignan (1) along with twenty known compounds. Comprehensive spectroscopic techniques such as UV, IR, NMR, HR-ESI-MS, ORD and ECD were used to identify their structures. Quantum chemical computations were used to assign the absolute configurations (AC) of (1). Using DP4+ analysis, the computed chemical shifts were used to pinpoint relative configuration. Compounds (1–6) were tested for biological activities. Compound (5) significantly decreased the release of lactate dehydrogenase (LDH) by 38% at a concentration of 10 μM, demonstrating that compound (5) had significant anti-inflammatory effects on the activation of the NLRP3 inflammasome, while no compound was found potent at a concentration of 200 μM against tyrosinase. Additionally, the chemotaxonomic significance of the isolated compounds was studied. [Display omitted] • One new phenyldihydronaphthalene-type lignan along with twenty known compounds from Vitex negundo var. Cannabifolia. • Spectroscopic analyses and quantum chemistry calculations were used to elucidate structures. • Compound 5 inhibited the release of lactate dehydrogenase (LDH) by 38% at a concentration of 10 μM. • Chemotaxonomic significance of the isolated compounds was discussed. [ABSTRACT FROM AUTHOR]

Abstract: Schilancidilactones A (1) and B (2), two novel tetranortriterpenoids possessing an unprecedented skeleton, have been isolated from the stems of Schisandra lancifolia. Their structures were elucidated on the basis of extensive spectroscopic analysis. The relative configurations of 1 were further determined by single-crystal X-ray crystallography. Compounds 1 and 2 were tested for their cytotoxicity against four tumor cell lines NB4, A549, SH-SY5Y, and PC-3, and compound 1 was further tested for its anti-HIV-1 activity. [Copyright &y& Elsevier]

Plants belonging to the genus Leonurus , also named motherwort, are traditionally used for anti-gynecological disorder in East Asia, and for sedative in Europe. Chemical investigation of the genus Leonurus not only enriched the natural products library, but also enlarged the pharmacological application of this traditional herb. In this review, we systematically summarized the structures of 259 compounds isolated from the genus Leonurus , featured with 147 labdane diterpenoids. The reported bioactivity studies up to 2017 are presented in the second part, with the main focus on the isolated compounds and also concerning the extracts. In addition to the traditional uterine contraction and sedative activity, recently the cardiovascular protection effect of leonurine has drawn most attention. Other than that, neuroprotection, anti-inflammation, anti-cancer, anti-platelet aggregation and many other activities have been assigned to various compounds from the genus Leonurus . Among 70 bioactivity references cited in this review, 57% of them were concentrated on two alkaloids (leonurine and stachydrine), whereas only 20% are about the 147 diterpenoids. Anti-inflammation is the major bioactivity discovered so far for the labdane diterpenoids from the genus Leonurus , whose further therapeutic potential still remains for exploration. [ABSTRACT FROM AUTHOR]

Eight new highly oxygenated lanostane triterpenes, gibbosic acids A–H ( 1 – 8 ), along with three known ones ( 9 – 11 ), were isolated from the fruiting body of Ganoderma gibbosum . The structures of new isolates were assigned by NMR and HRESIMS experiments. The absolute configurations of 1 were further confirmed by single crystal X-ray diffraction data and computational ECD methods. Immunoregulatory effect and anti-inflammatory activities of these compounds were screened in murine lymphocyte proliferation assay and in lipopolysaccharide (LPS)-stimulated RAW-264.7 macrophages, respectively. Compound 2 exhibited immunostimulatory effect both in lymphocyte proliferation assay without any induction and ConA-induced mitogenic activity of T-lymphocyte, and the proportion of lymphocyte proliferation at the concentration of 0.1 μM are 20.01% and 21.40%, respectively. [ABSTRACT FROM AUTHOR]

A phytochemical investigation to obtain bioactive substances as lead compounds or agents for anti-inflammatory led to the obtainment of eleven previously undescribed clerodane diterpenoids, named caseatardies A-K (1 − 11), and four known clerodane diterpenoids (12 – 15) from the twigs and leaves of Casearia tardieuae. The structural elucidation of these clerodane diterpenoids was based on 1D and 2D-NMR spectroscopy (COSY, HSQC, HMBC and ROESY) as well as high resolution mass spectrometry (HR-ESI-MS). The relative configurations were defined by ROESY correlations. The anti-inflammatory activity of all the isolated compounds was screened and compound 15 decreased LDH level in a dose-dependent manner, showing IC 50 value of 2.89 μM. [Display omitted] • Eleven new clerodane diterpenoids with conjugated diene side chain at C-9 were isolated from Casearia tardieuae. • The compound 15 showed potent inhibitory activity against pyroptosis by blocking NLRP3 inflammasome activation. • Their structures were established by elucidated by 1D, 2D-NMR and HR-ESI-MS analyses. [ABSTRACT FROM AUTHOR]

Ten new prenylated flavonoids, named denticulains A-J (1−10), together with seven known prenylated flavonoids (11–17) were isolated from Macaranga denticulata. Their structures were elucidated on the basis of detailed spectroscopic analysis and by comparison with literature data. In addition, compounds 1 and 14 inhibited the proliferation of SW620 and HCT-116 cell lines with an IC 50 value of 46.08 μM and 56.83 μM, respectively. [Display omitted] • Ten new prenylated flavonoids were isolated from Macaranga denticulata. • Some compounds have week anticancer activities. [ABSTRACT FROM AUTHOR]

A phytochemical investigation was conducted on Euphorbia helioscopia , resulting in the isolation of thirteen compounds, including nine undescribed diterpenoids, Euphzycopias A − I (1 – 9), of which the skeletons of compounds 1 – 4 were found in E. helioscopia L. Compounds 1 – 3 had 5/7/6 cyclic systems, while compound 4 had a 4/11 polycyclic system with a 4,7-cyclic ether between C-4 and C-7. The anti-inflammasome test using the isolated compounds (1–6, 8–13) showed that the diterpenes from E. helioscopia L. had a strong inhibitory effect on NLRP3 inflammasomes with IC 50 values of 3.34–14.92 μM. [Display omitted] • Nine undescribed diterpenoids were isolated from Euphorbia helioscopia L. • The skeletons of the first four compounds first appeared in the genus Euphorbia L. • Some compounds had significant anti-inflammatory activity on NLRP3 inflammasome. [ABSTRACT FROM AUTHOR]

Abstract: A new benzophenone C-glycoside, malaferin A (1), and two new epicatechin derivatives, malaferin B (2) and malaferin C (3), together with five known compounds were isolated from Malania oleifera. In addition, (−)-epicatechin-3-O-benzoate (6) was isolated for the first time from a natural resource. Structures of 1–3 were determined on the basis of their spectroscopic methods, including 1D and 2D NMR techniques. All of the compounds were evaluated for anti-HIV activities. [Copyright &y& Elsevier]

Nine new diterpenoids, Rubellacrns A − I (1–9), including five isopimaranes (1–4, 9), four pimaranes (5–8), together with five known isopimarane analogues (10–14), were isolated from Callicarpa rubella. The structures of these compounds were unambiguously established by HR-ESIMS and NMR spectroscopic data, the absolute configurations of compounds 5 and 9 were determined by ECD. All the isolated compounds were tested for their anti-inflammatory effects and compounds 2 and 11–14 showed NLRP3-inflammasome inhibitory activity with IC 50 values ranging from 7.02 to 14.38 μM. Unlabelled Image • Nine new diterpenoids were isolated from Callicarpa rubella. • The absolute configuration of 5 and 9 was deduced by ECD. • The new compound 2 showed potent inhibition of inflammasome activation. [ABSTRACT FROM AUTHOR]