•LPM and LPG were prepared from alginate and studied side-by-side.•LPM and LPG derivatives containing −PO32−, −PO2H− and −SO3− were synthesized.•SO3− modification of LPM and LPG enhanced the anticoagulant and FGFs/FGFR1c signaling activation activities.•Sulfated LPG had better heparin-like activities than sulfated LPM.A series of low-molecular-weight polymannuronate (LPM) and polyguluronate (LPG) polyanionic derivatives, including LPM/LPG phosphate (LPMP/LPGP), LPM/LPG H-phosphonate (LPMHP/LPGHP) and LPM/LPG sulfate (LPMS/LPGS), were prepared as heparinoids by chemical modification of LPM and LPG. The structures and characteristics of LPM, LPG and their derivatives were elucidated based on high performance gel permeation chromatography (HPGPC), fourier transform infrared spectroscopy (FT-IR), nuclear magnetic resonance spectroscopy (NMR) and polyacrylamide gel electrophoresis (PAGE). In order to test the heparin-like activities of these derivatives and to reveal the activities affected by substituent groups and PM/PG polysaccharide backbones, the anticoagulant activities and FGF/FGFR1c signaling activation abilities were evaluated in vitro. The results showed that sulfate group was the best substituent group to improve the heparin-like activities of LPM/LPG compared with the other two anionic groups. The results also showed that sulfated derivative based on PG structure had better activities than that based on PM structure.

•A novel method for determination of monosaccharides in sulfated chitosan was developed.•The structure and sulfated degree of chitosan were also revealed.•The reliability of the method was confirmed by online LC–MS analysis.•The accuracy of our measurement was improved compared to established methods.•This method could be used by any laboratory equipped with a HPLC and an online UV detector.Chemically sulfated chitosans are important biomaterials. However, a reliable analytical method for quality control over such compounds is still lacking. In this study, we prepared four different kinds of selectively sulfated chitosans and developed a novel method to analyze their monosaccharide compositions by HPLC. In this method, nitrous acid was used to generate 2, 5-hydro mannose (M), 3-O-sulfated M (M3), 6-O-sulfated M (M6), and 3, 6-O-disulfated M (M9) from the sulfated chitosans. PMP, that is 1-phenyl-3-methyl-5-pyrazolone with a UV absorbance at 245 nm, was used to label all the Ms quantitatively. The monosaccharide compositions for each sulfated chitosan were obtained by C18 HPLC separation and online UV detection of all PMP-labeled Ms. The identities of all Ms were confirmed by MS analysis with the help of standard Ms generated from a heparin pentasaccharide and chitosan. The overall results indicated that the newly developed method had advantages over 13C NMR in defining the monosaccharide compositions of sulfated chitosans and was useful for quality control purpose.

•Novel isothiouronium-modified pyrimidine-substituted curcumin analogs were synthesized.•Isothiouronium modifications greatly enhanced anticancer activities of the analogs.•Only the fluorescence compound with isothiouronium modification showed unique Golgi localization.•The isothiouronium analogs were novel Golgi staining compounds.•The isothiouronium analogs were useful in studying the biological functions of Golgi.Most of protein post-translational modifications occur in the Golgi and many human diseases are associated with abnormal Golgi function or improper post translational modifications of proteins in the Golgi. In this study, we designed and synthesized 4 × 6 series of novel isothiouronium-modified (E,E)-4,6-bis(styryl)-pyrimidine analogs and found that they localized at the Golgi as visualized by the intrinsic fluorescence of the analogs. The isothiouronium-modified analogs had potent cytotoxicity in both normal (Chinese Hamster Ovary or CHO) and cancer cells. Furthermore, permethylated isothiouronium-modified analogs showed cancer cell-selective cytotoxicity. The molecular mechanisms underlying Golgi localization of isothiouronium-modified compounds were investigated using 7 CHO and 4 human cancer cell lines and the results indicated that the compounds had binding partners in the Golgi. Thus, isothiouronium-modified analogs might be promising anticancer agents, novel Golgi staining reagents, and useful research tools for studying Golgi functions in normal or cancer cells and in Golgi-related human diseases.

•PSS oligosaccharides were prepared by a solid phase acid degradation method.•Thirteen PSS oligosaccharides fractions were obtained and characterized by ESI-MS.•Molecular weight and sulfate group are important to the anticoagulation of PSS.•Several PSS oligosaccharides presented significant cell proliferation stimulation.Propylene glycol alginate sodium sulfate (PSS), prepared by chemical sulfation of alginate, has been used for treating cardiovascular diseases in China for nearly 30 years. In the current study, the PSS was hydrolyzed partially by an environment-friendly solid phase acid degradation method, and then separated by using a Bio-Gel P6 chromatographic column. Thirteen PSS oligosaccharide fractions were obtained and characterized by ESI-MS. The results of different coagulation assays showed that a high molecular weight and a higher degree of sulfation were essential for the anticoagulant activity of the PSS because the PSS oligosaccharides exhibited no detectable anticoagulant activity. In contrast, not only PSS but also certain oligosaccharides showed significant activities in stimulation of FGF1, 2, 7, 8, 9 or 10 induced cell proliferation in FGFR1c-expressing BaF3 cells. Such properties made the PSS and its oligosaccharides promising compounds in the regulation of FGF-dependent development, treatment of cancer, and wound healing processes.

•A series of new benzoic and cinnamic acid analogs of PGG were synthesized.•The SAR of PGG analogs for antitumor and antioxidant activity has been studied.•PGG had highest cytotoxicities in HCT116 and A549 cells.•Pentavanilloylglucose was most effective at killing HT29 and H1299 cells.•Different molecular targets might be involved for antitumor and antioxidant activities.1,2,3,4,6-Pentakis[-O-(3,4,5-trihydroxybenzoyl)]-α,β-D-glucopyranose (PGG) 12 has been reported for its antioxidant activities, where the free OH groups in PGG seem to be critical for activities. To explore PGG-based compounds as chemotherapeutic agents and to analyze the contribution of specific OH groups in PGG for anti-cancer activities, we designed and synthesized a series of 27 benzoic and cinnamic acid analogs of PGG. These analogs were tested for cytotoxicities against two human lung (A549 and H1299) and two human colon (HCT116 and HT29) cancer cell lines. Compound 12 (PGG) had highest cytotoxicities against HCT116 and A549 cells with IC50 of 1.61 µM and 3.02 µM, respectively. In contrast, the compound 16 (1,2,3,4,6-pentakis[-O-(4-hydroxy-3-methoxybenzoyl)]-α,β-D-glucopyranose, PVG) was most effective at killing HT29 and H1299 cells with IC50 of 1.76 µM and 3.65 µM, respectively, indicating the mutual contribution of m-methoxy and p-hydroxy groups to the observed cytotoxicities. Moreover, cinnamic acid analogs were less active than the benzoic acid analogs evidenced by higher IC50 values. Furthermore, in cinnamic acid analogs the hydrogenation of double bond to saturated 2-C side chain enhance the cytotoxicities in all four cell lines. Compounds also possess good anti-oxidant and reducing activities. Compound 12 and 26 show the highest antioxidant and reducing activities.

•Astaxanthin inhibited the L-glutamate cytotoxicity via multiple signaling pathways.•The LDH release and ROS production were reduced.•The activities of antioxidant enzymes SOD and GR were enhanced.•ROS associated NF-κB and MAPK pathways were down-regulated.•Bax/Bcl-2 ratio, caspase-3 activation and Ca2+ influx were depressed.Astaxanthin, a carotenoid extensively found in marine organisms and increasingly used as a dietary supplement, has been reported to have neuroprotective effect. In this study, the neuroprotective effects and mechanisms of astaxanthin against glutamate-induced neurotoxicity were explored. The results showed that pretreatment with astaxanthin inhibited neuronal PC12 cell death induced by L-glutamate and reduced the production of reactive oxygen species (ROS) significantly. Astaxanthin prevented glutamate-induced apoptosis by depressing the elevation of Bax/Bcl-2 ratio, caspase-3 activation and Ca2+ influx. Moreover, the loss of mitochondrial membrane potential (MMP) as well as the activation of ROS associated NF-κB and MAPK pathways were also inhibited upon treatment with astaxanthin. Therefore, the neuroprotective effects reflected the ability of astaxanthin in the regulation of multiple signaling pathways that protect mitochondria as well as cellular damage induced by L-glutamate. Thus, astaxanthin has the potential to be used as a prophylactic or remediation agent against neuronal disorders.

Heparin and low molecular weight heparin have been used widely in clinical therapy as anticoagulants in cardiovascular disease and in hemodialysis. Crude heparin is usually prepared from porcine intestinal mucosa. Purified heparin is a mixture of polysaccharides consisting mainly of repeating GlcNS(6S)-IdoA2S disaccharides and other disaccharides with different GlcNAc/GlcNS±3S±6S-GlcA/IdoA±2S residues. Heparin injections are prepared by purification and then sterilization of ungraded heparin. Low molecular weight heparins are dominant heparin-based drugs used clinically, which are prepared by degrading heparin into smaller molecules. As a result, low molecular weight heparins share the same major disaccharides with heparin, but may have different reducing and non-reducing ends due to different preparation methods. In the current study, we analyzed the disaccharide composition of clinically used heparin and heparin-based drugs. Heparinase I, II and III were used to degrade all heparin and heparin-based drugs including heparin sodium injection, Enoxaparin sodium injection, Nadroparin calcium injection, Dalteparin sodium injection, and Fondaparinux sodium injection into disaccharides. All the degraded products were analyzed by strong anion exchange-high performance liquid chromatography (SAX-HPLC) equipped with an online UV-detector. Commercially available unsaturated disaccharide standards were then used for structural identification. Furthermore, unusual disaccharides present in Nadroparin, Dalteparin and Fondaparinux were confirmed by reversed-phase ion-pair HPLC coupled with mass spectrometry analysis. The developed method produced detailed structural information, which should be useful for quality control of heparin and heparin-based drugs.Heparinase I, II and III were used to degrade all heparin and heparin-based drugs. The degraded products were analyzed by strong anion exchange-high performance liquid chromatography (SAX-HPLC) equipped with UV-detector. Unusual disaccharides were confirmed by reversed-phase ion-pair HPLC coupled with mass spectrometry analysis (LC-MS). The developed method is very useful for quality control of heparin drugs.

•The TFA catalyzed 3-vinylindoles cyclodimerization was investigated.•Benzyl and phenyl substituted in 1,2-C of compounds gave highest cytotoxic effect.•F-benzyl and F-phenyl substitution in 1,2-C of compound altered EGFR expression.We synthesized a series of novel 3-indolyl cyclopent[b]indoles by trifluoroacetic acid mediated cyclodimerizations. The reaction showed high stereoselectivity and moderate to good yields. The influencing factors for stereoselectivity were systematically analyzed and a stepwise reaction mechanism was proposed. The cell viability tests in two colon and two lung cancer cell lines indicated the 1-benzyl-2-phenyl-group in 3-indolyl cyclopent[b]indoles was critical for the observed lower IC50s in these compounds. Western blot analysis demonstrated that the compound inhibited the expression and phosphorylation of EGFR through altered HSP90 expression. Further cell cycle and cell cycle check point protein analyses showed expected anti-cellular proliferation and cell cycle arresting properties associated with suppressed EGFR expression and phosphorylation. These data revealed a novel molecular mechanism explaining the observed cytotoxicities for these compounds.Compound 8 and 9 inhibited cancer cell proliferation. Western blot analysis demonstrated that compound 9 altered the expression and phosphorylation of EGFR.

The synthesis of a 4 × 4 series of novel quindoline derivatives with or without boronic acid modifications and their cytotoxicities, cellular localizations, and implications on cancer cells are presented and discussed.

The synthesis of a 4 × 4 series of novel quindoline derivatives with or without boronic acid modifications and their cytotoxicities, cellular localizations, and implications on cancer cells are presented and discussed.