Human KB Research Articles

Limonium brasiliense rhizomes extract against virulence factors of Porphyromonas gingivalis: Inhibition of gingipains, bacterial adhesion, and biofilm formation

Periodontitis is clinically characterized by destruction of the tooth support system and tooth loss. Porphyromonas gingivalis (Pg) plays a dominant role in periodontitis. Fractions and isolated compounds from an acetone-water extract of the roots of Limonium brasiliense (Lb) were tested in vitro for their anti-adhesive capacity against Pg on human KB buccal cells, influence on gingipains, the main virulence factors of Pg, and biofilm formation. Fractions EAF and FLB7 (50 μg/mL) reduced the bacterial adhesion of Pg to KB cells significantly (63 resp. 70%). The proanthocyanidin samarangenin A inhibited the adhesion (72%, 30 μM), samarangenin B (71%, 20 μM), and the flavan-3-ol epigallocatechin-3-O-gallate (79%, 30 μM). Fraction AQF, representing hydrophilic compounds, reduced the proteolytic activity of Arginin-specific gingipain (IC50 12.78 μg/mL). Fractions EAF and FLB7, characterized by lipohilic constituents, inhibited Arg-gingipain (IC50 3 μg/mL). On Lysine-specific gingipain, AQF has an IC50 15.89, EAF 14.15, and FLB7 6 μg/mL. The reduced bacterial adhesion is due to a strong interaction of proanthocyanidins with gingipains. AQF, EAF, and FLB7 significantly inhibited biofilm formation: IC50 11.34 (AQF), 11.66 (EAF), and 12.09 μg/mL (FLB7). In silico analysis indicated, that the polyphenols act against specific targets of Pg, not affecting mammalian cells. Therefore, Lb might be effective for prevention of periodontal disease by influencing virulence factors of Pg.

Negative regulation of thyroid adenoma-associated protein (THADA) in the cardiac glycoside-induced anti-cancer effect

Cardiac glycosides, known as inhibitors of Na+,K+-ATPase, have anti-cancer effects such as suppression of cancer cell proliferation and induction of cancer cell death. Here, we examined the signaling pathway elicited by cardiac glycosides in the human hepatocellular carcinoma HepG2 cells and human epidermoid carcinoma KB cells. Three kinds of cardiac glycosides (ouabain, oleandrin, and digoxin) inhibited the cancer cell proliferation and decreased the expression level of thyroid adenoma-associated protein (THADA). Interestingly, the knockdown of THADA inhibited cancer cell proliferation, and the proliferation was significantly rescued by re-expression of THADA in the THADA-knockdown cells. In addition, the THADA-knockdown markedly decreased the expression level of L-type amino acid transporter LAT1. Cardiac glycosides also reduced the LAT1 expression. The LAT1 inhibitor, JPH203, significantly weakened the cancer cell proliferation. These results suggest that the binding of cardiac glycosides to Na+,K+-ATPase negatively regulates the THADA-LAT1 pathway, exerting the anti-proliferative effect in cancer cells.

Multifunctional curcumin mediated zinc oxide nanoparticle enhancing biofilm inhibition and targeting apoptotic specific pathway in oral squamous carcinoma cells.

Oral health remains a significant global concern with the prevalence of oral pathogens and the increasing incidence of oral cancer posing formidable challenges. Additionally, the emergence of antibiotic-resistant strains has complicated treatment strategies, emphasizing the urgent need for alternative therapeutic approaches. Recent research has explored the application of plant compounds mediated with nanotechnology in oral health, focusing on the antimicrobial and anticancer properties. In this study, curcumin (Cu)-mediated zinc oxide nanoparticles (ZnO NPs) were synthesized and characterized using SEM, EDAX, UV spectroscopy, FTIR, and XRD to validate their composition and structural features. The antioxidant and antimicrobial activity of ZnO-CU NPs was investigated through DPPH, ABTS, and zone of inhibition assays. Apoptotic assays and gene expression analysis were performed in KB oral squamous carcinoma cells to identify their anticancer activity. ZnO-CU NPs showcased formidable antioxidant prowess in both DPPH and ABTS assays, signifying their potential as robust scavengers of free radicals. The determined minimal inhibitory concentration of 40µg/mL against dental pathogens underscored the compelling antimicrobial attributes of ZnO-CU NPs. Furthermore, the interaction analysis revealed the superior binding affinity and intricate amino acid interactions of ZnO-CU NPs with receptors on dental pathogens. Moreover, in the realm of anticancer activity, ZnO-CU NPs exhibited a dose-dependent response against Human Oral Epidermal Carcinoma KB cells at concentrations of 10µg/mL, 20µg/mL, 40µg/mL, and 80µg/mL. Unraveling the intricate mechanism of apoptotic activity, ZnO-CU NPs orchestrated the upregulation of pivotal genes, including BCL2, BAX, and P53, within the KB cells. This multifaceted approach, addressing both antimicrobial and anticancer activity, positions ZnO-CU NPs as a compelling avenue for advancing oral health, offering a comprehensive strategy for tackling both oral infections and cancer.

Zinc oxide nanoparticles functionalized with cinnamic acid for targeting dental pathogens receptor and modulating apoptotic genes in human oral epidermal carcinoma KB cells.

Oral diseases are often attributed to dental pathogens such as S. aureus, S. mutans, E. faecalis, and C. albicans. In this research work, a novel approach was employed to combat these pathogens by preparing zinc oxide nanoparticles (ZnO NPs) capped with cinnamic acid (CA) plant compounds. The synthesized ZnO-CA NPs were characterized using SEM, FTIR, and XRD to validate their composition and structural features. The antioxidant activity of ZnO-CA NPs was confirmed using DPPH and ABTS free radical scavenging assays. The antimicrobial effects of ZnO-CA NPs were validated using a zone of inhibition assay against dental pathogens. Autodock tool was used to identify the interaction of cinnamic acid with dental pathogen receptors. ZnO-CA NPs exhibited potent antioxidant activity in both DPPH and ABTS assays, suggesting their potential as powerful antioxidants. The minimal inhibitory concentration of ZnO-CA NPs against dental pathogens was found 25µg/mL, indicating their effective antimicrobial properties. Further, ZnO-CA NPs showed better binding affinity and amino acid interaction with dental pathogen receptors. Also, the ZnO-CA NPs exhibited dose-dependent (5µg/mL, 15µg/mL, 25µg/mL, and 50µg/mL) anticancer activity against Human Oral Epidermal Carcinoma KB cells. The mechanism of action of apoptotic activity of ZnO-CA NPs on the KB cells was identified through the upregulation of BCL-2, BAX, and P53 genes. This research establishes the potential utility of ZnO-CA NPs as a promising candidate for dental applications. The potent antioxidant, anticancer, and effective antimicrobial properties of ZnO-CA NPs make them a valuable option for combating dental pathogens.

Molecular perspective on starfish tissue extracts: Targeting human carcinoma KB cells for anticancer therapy

The marine environment is rich in natural bioactive compounds, including zebrafish and starfish species, which have garnered attention in drug research for their remarkable tissue regeneration abilities. Zebrafish, in particular, share a genetic resemblance of around 70% with humans. We chose to investigate Luidia maculata, a starfish species, due to its remarkable tissue regeneration abilities and the potential bioactive compounds it holds, making it a promising candidate for anticancer and antioxidant therapies. Human KB carcinoma cells were subjected to L. maculata tissue extracts to assess cytotoxicity using the MTT test. Intracellular ROS levels were measured via DCFH-DA, and mitochondrial membrane potential changes were evaluated using Rh-123 staining. Oxidative DNA damage was examined with the comet test, while morphological apoptotic changes were observed through the AO/EtBr dual staining technique. The active compounds in the starfish extracts were identified using HPLC, GC–MS/MS, and FTIR analyses.The bioactive fractions extracted from L. maculata demonstrated significant anti-proliferative effects on KB carcinoma cells, inducing apoptosis. These fractions led to a notable increase in intracellular ROS levels, resulting in alterations in mitochondrial membrane potential and oxidative DNA damage in the cells. Upregulation of Bax/Caspase 3 protein expression and downregulation of Bcl-2 protein expression indicated the involvement of apoptotic pathways. Comprehensive analyses confirmed 35 starfish-derived anticancer compounds that inhibit cell proliferation, induce apoptosis, and target cancer-related pathways. Additionally, our study underscores the antioxidant potential of L. maculata starfish extracts, offering insights into marine organism-based therapies with promising medical applications.

Design, synthesis, and biological evaluation of simplified tetrahydroisoquinoline analogs.

A series of tetrahydroisoquinoline derivatives were prepared and their antitumor activity was studied against several human carcinoma cell lines, including Ketr3, BEL-7402, BGC-823, KB, HCT-8, MCF-7, HeLa, A2780, A549, and HT-1080. Compound 20, an analog of phthalascidin 650, exhibited good broad-spectrum antitumor activity in vitro. However, compounds 19 and 21, in which the side chains at C-22 are simplified, showed no obvious antitumor activity, indicating that the C-22 side chain of this type of compound has a greater impact on its activity. The difference in the in vivo activity between compound 20 and phthalascidin 650 also shows a significant effect of the substituents on the skeleton structure on the in vivo activity.

Folate-Targeted Nanoliposomal Chemophototherapy.

Light-responsive liposomes have been developed for the on-demand release of drugs. However, efficient delivery of chemotherapeutic drugs to tumor for cancer theranostics remains a challenge. Herein, folic acid (FA), an established ligand for targeted drug delivery, was used to decorate light-sensitive porphyrin-phospholipid (PoP) liposomes, which were assessed for FA-targeted chemophototherapy (CPT). PoP liposomes and FA-conjugated PoP liposomes were loaded with Doxorubicin (Dox), and physical properties were characterized. In vitro, FA-PoP liposomes that were incubated with FA receptor-overexpressing human KB cancer cells showed increased uptake compared to non-targeted PoP liposomes. Dox and PoP contributed towards chemophototherapy (CPT) in vitro, and PoP and FA-PoP liposomes induced cell killing. In vivo, mice bearing subcutaneous KB tumors treated with PoP or FA-PoP liposomes loaded with Dox, followed by 665 nm laser treatment, had delayed tumor growth and improved survival. Dox delivery to tumors increased following laser irradiation for both PoP and FA-PoP liposomes. Thus, while Dox-FA-PoP liposomes were effective following systemic administration and local light irradiation in this tumor model, the FA targeting moiety did not appear essential for anti-tumor responses.

Mechanistic investigation of photodynamic therapy using Visudyne in human KB carcinoma cells

Photodynamic therapy is a therapy that utilizes a specialized drug, a photosensitizer, which is not toxic by itself, but upon activation with light, is activated and leads to the production of singlet oxygen species. This production of singlet oxygen species starts a cascade that leads to cell death. Photodynamic therapy is a potential treatment for cancer patients, and it might be helpful to promote human health by providing alternative treatment to cancer. In-vitro study with Visudyne (VD) in KB carcinoma cells unveiled the mechanism of cell injury to cell death upon photodynamic therapy (PDT). In this study, we investigated real time monitoring of the production of singlet oxygen (SO), reactive oxygen species (ROS), mitochondria integrity and chromatin integrity in VD treated live cells by irradiating with a mercury lamp light source and 665–675 nm and 480–560 nm emission filter. Upon PDT we also observed cytoskeleton remodeling and cytochrome –C release using immunofluorescence techniques. We investigate the cytotoxicity of PDT and performed quantitative analysis for SO, ROS and mitochondrial potential change using colocalization analysis between VD and mitochondria.

Lignans and some other non-alkaloid compounds from the stem bark of Zanthoxylum rhetsa and their biological activities

Four lignans, asarinin (1), horsfieldin (2), 5-(4-(3,4,5-trimethoxyphenyl)hexahydrofuro[3,4-c]furan-1-yl)benzo[d][1,3]dioxole (3), 5-(4-(3,5-dimethoxyphenyl)hexahydrofuro[3,4-c]furan-1-yl)benzo[d][1,3]dioxole (4), and four non-alkaloid compounds, piperonylic acid (5), hesperidin (6), syringin (7), and β-sitosterol (8) were isolated from the stem bark of Zanthoxylum rhetsa grown in Vietnam. Their chemical structures were elucidated by spectroscopic analysis and compared with the references. Except for compound 6, all the remaining compounds (1–5, 7, and 8) were isolated for the first time from Z. rhetsa. The isolated compounds were tested for their cytotoxic activity against three human cancer cell lines, LU-1, Hep-G2, and KB. Compound 5 showed moderate cytotoxic activity against all three cell lines with IC50 values ranging from 48.13 to 49.06 µg mL−1. Notably, compound 6 demonstrated selective cytotoxicity against LU-1, Hep-G2, and KB cancer cell lines (IC50 66.48–67.41 µg mL−1) while non-toxic toward normal Vero cell. Compound 6 also exhibited its ability to inhibit main protease (Mpro) enzyme in vitro with an IC50 value of 55.49 µg mL−1 and in silico with the binding affinity toward targeted protein of −14.36 kcal mol−1.

Nature-Inspired Chemistry of Complex Alkaloids: Combining Targeted Molecular Networking Approach and Semisynthetic Strategy to Access Rare Communesins in a Marine-Derived Penicillium expansum.

Communesins are rare alkaloids isolated from fungi of the genus Penicillium. In this work, the extract of a marine-derived Penicillium expansum strain was studied using targeted molecular networking approach allowing to detect 65 communesins including 55 new ones. A fragmentation pattern for dimethylvinyl communesins was established and a script was implemented allowing to predict the structure and map all communesins in a global molecular network. A semisynthetic strategy was carried out to obtain some minor congeners from the two isolated communesins A and B. Nine communesins were then synthetised: two of them were already described as produced by the studied strain; four are new natural products which occurrence in the extracts was confirmed; three are new semi-synthetic analogues never described so far. These communesins were evaluated for their cytotoxicity on two human cancer cell lines KB and MCF-7 leading to a preliminary study of their structure-activity relationships.

Enhancement of in-vitro anti-oral cancer activities of silymarin using dispersion of nanostructured lipid carrier in mucoadhesive in-situ gel

Silymarin (SME) shows multiple therapeutic actions against several cancers, however, low aqueous solubility and poor bioavailability issues restrict its clinical use. In this study, SME was loaded in nanostructured lipid carriers (NLCs) and further incorporated in mucoadhesive in-situ gel (SME-NLCs-Plx/CP-ISG) for localized treatment of oral cancer. Using a 33 Box-Behnken design (BBD), an optimized SME-NLC formula was developed with the ratios of solid lipids, surfactant concentration, and sonication time as independent variables, while particle size (PS), polydispersity index (PDI), and % encapsulation efficiency (EE) as dependent variables, resulting in 315.5 ± 0.1 nm PS, 0.341 ± 0.01 PDI, and 71.05 ± 0.05 % EE. Structural studies confirmed the formation of SME-NLCs. SME-NLCs incorporated in-situ gel demonstrated a sustained release for SME, indicating enhanced retention on the buccal mucosal membrane. The in-situ gel containing SME-NLCs showed a marked decrease in IC50 value (24.90 ± 0.45 µM) than SME-NLCs (28.40 ± 0.89 µM) and plain SME (36.60 ± 0.26 µM). The studies demonstrated that Reactive oxygen species (ROS) generation potential and SME-NLCs-Plx/CP-ISG induced apoptosis at Sub-G0 phase owing to higher penetration of SME-NLCs led to higher inhibition against human KB oral cancer cells. Therefore, SME-NLCs-Plx/CP-ISG can be the alternative to chemotherapy and surgery with site-specific delivery of SME to oral cancer patients.

Separation and Purification of Antioxidant Peptide from Fermented Whey Protein by Lactobacillus rhamnosus B2-1.

In this study, a antioxidant activity peptide fraction was separated and purified from metabolites of whey protein fermented by Lactobacillus rhamnosus B2-1. The fermentation sample was separated by macroporous resin D101 and Sephadex G-15. The collected fractions were tested for antioxidant and antitumor activities. In order to test the antioxidant activity of fractions, Hydroxyl (·OH), 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid (ABTS), and Oxygen Radical Absorbance Capacity (ORAC) were used. The final purified peptide B11 showed highest ABTS and ·OH radical scavenging rate by 84.36±1.89% and 62.43±2.64%, respectively, and had an ORAC activity of 1,726.44± 2.76 μM Trolox equivalent/g. Further, the inhibitory effect of B11 on the proliferation of LoVo human colon cancer cells, KB and Cal-27 human oral cancer cells were enhanced with increasing concentrations of B11. B11 contains 51.421% amino acids, with Glu and Asp being the major constituents. In this study, we obtained peptide fraction B11 with antioxidant activity, which is promising for development.

Cyclometalated platinum(II) complexes bearing natural arylolefin and quinolines ligands: Synthesis, characterizations, and in vitro cytotoxicity

Nine new cyclometalated platinum(II) complexes of the formula [PtCl(arylolefin)(Q)] (2, 3) and [Pt(arylolefin)(N,O)] (4–10) (arylolefinH: eugenoxyacetic acid, isopropyl eugenoxyacetate; Q: quinoline; (N,OH): quinolin-8-ol, 2-methylquinolin-8-ol, 5,7-dichloroquinloin-8-ol and quinoline-2-carboxylic acid] were synthesized and fully characterized by EA, ESI mass spectrometry, IR and NMR spectroscopy and single-crystal X-ray diffraction for 3, 7 and 10. The results show that the arylolefin binds with PtIIvia the C5 atom of the phenyl ring and the CC allyl in all the synthesized complexes. Quinoline coordinates with PtIIvia its N atom in 2, 3, while deprotonated (N,OH) coordinates with PtIIvia both the N and O atoms in 4–10. The N atom of Q and (N,O) in all complexes are at the cis position with respect to the allyl group of the arylolefin. The XRD confirms the square-planar coordination of PtII and trans position of the arylolefin and quinoline ligands. The results of in vitro cytotoxicity tests against human cancer cell lines KB and Lu of 2, 4–8 indicate that 4 and 5 exhibit the highest activities against Lu and KB cell lines with the IC50 values of 7.1 and 4.1 µM, respectively, which are approximately 6 and 4 times lower than cisplatin.

Microstructured Polymer System Containing Proanthocyanidin-Enriched Extract from Limonium brasiliense as a Prophylaxis Strategy to Prevent Recurrence of Porphyromonas gingivalis.

Periodontal diseases are a global oral health problem affecting almost 10% of the global population. Porphyromonas gingivalis is one of the main bacteria involved in the initiation and progression of inflammatory processes as a result of the action of the cysteine proteases lysin- and arginine-gingipain. Surelease/polycarbophil microparticles containing a lyophilized proanthocyanidin-enriched fraction from the rhizomes of Limonium brasiliense, traditionally named "baicuru" (ethyl acetate fraction), were manufactured. The ethyl acetate fraction was characterized by UHPLC by the presence of samarangenins A and B (12.10 ± 0.07 and 21.05 ± 0.44%, respectively) and epigallocatechin-3-O-gallate (13.44 ± 0.27%). Physiochemical aspects of Surelease/polycarbophil microparticles were characterized concerning particle size, zeta potential, entrapment efficiency, ethyl acetate fraction release, and mucoadhesion. Additionally, the presence of the ethyl acetate fraction-loaded microparticles was performed concerning potential influence on viability of human buccal KB cells, P. gingivalis adhesion to KB cells, gingipain activity, and P. gingivalis biofilm formation. In general, all Surelease/polycarbophil microparticles tested showed strong adhesion to porcine cheek mucosa (93.1 ± 4.2% in a 30-min test), associated with a prolonged release of the ethyl acetate fraction (up to 16.5 ± 0.8% in 24 h). Preincubation of KB cells with Surelease/polycarbophil microparticles (25 µg/mL) resulted in an up to 93 ± 2% reduced infection rate by P. gingivalis. Decreased activity of the P. gingivalis-specific virulence factors lysin- and arginine-gingipain proteases by Surelease/polycarbophil microparticles was confirmed. Surelease/polycarbophil microparticles decreased biofilm formation of P. gingivalis (97 ± 2% at 60 µg/mL). Results from this study prove the promising activity of Surelease/polycarbophil microparticles containing ethyl acetate fraction microparticles as a prophylaxis strategy to prevent the recurrence of P. gingivalis.

Effect of PEG anchor in PEGylation of folate-modified cationic liposomes with PEG-derivatives on systemic siRNA delivery into the Tumor

In this study, we prepared small interfering RNA (siRNA)/cationic liposome complexes (lipoplexes) modified with folate (FA)-polyethylene glycol (PEG, MW 2000, 3400 or 5000)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE) to facilitate their uptake into tumor cells via folate receptor (FR), and with PEG1600-cholesterol (PEG1600-Chol) or PEG2000-chondroitin sulfate conjugate (PEG2000-CS), to enhance their systemic stability. Among the FA-PEG-modified siRNA lipoplexes, 0.5 mol% FA-PEG5000-DSPE-modified lipoplexes with 2.5 mol% PEG2000-CS or PEG1600-Chol (LP-0.5F5/2.5P2-CS and LP-0.5F5/2.5P1.6-CL, respectively) exhibited selective growth inhibition of human nasopharyngeal carcinoma KB cells through transduction with polo-like kinase 1 (PLK1) siRNA. Furthermore, the LP-0.5F5/2.5P2-CS and LP-0.5F5/2.5P1.6-CL lipoplexes exhibited decreased agglutination with erythrocytes through PEGylation, and markedly decreased the accumulation of siRNA in murine lungs after systemic injection. Finally, systemic injection of LP-0.5F5/2.5P2-CS and LP-0.5F5/2.5P1.6-CL lipoplexes resulted in accumulation of siRNA in KB tumor xenografts. These findings suggest that PEGylation of FA-PEG5000-DSPE-modified siRNA lipoplexes with PEG2000-CS or PEG1600-Chol might improve their systemic stability without the loss of selective transfection activity in tumor cells.

Development of a cancer cells self‑activating and miR‑125a‑5p expressing poly‑pharmacological nanodrug for cancer treatment.

Cancer cells can acquire resistance to targeted therapeutic agents when the designated targets or their downstream signaling molecules develop protein conformational or activity changes. There is an increasing interest in developing poly-pharmacologic anticancer agents to target multiple oncoproteins or signaling pathways in cancer cells. The microRNA 125a-5p (miR-125a-5p) is a tumor suppressor, and its expression has frequently been downregulated in tumors. By contrast, the anti-apoptotic molecule BIRC5/SURVIVIN is highly expressed in tumors but not in the differentiated normal tissues. In the present study, the development of a BIRC5 gene promoter-driven, miR-125a-5p expressing, poly-L-lysine-conjugated magnetite iron poly-pharmacologic nanodrug (pL-MNP-pSur-125a) was reported. The cancer cells self-activating property and the anticancer effects of this nanodrug were examined in both the multidrug efflux protein ABCB1/MDR1-expressing/-non-expressing cancer cells in vitro and in vivo. It was demonstrated that pL-MNP-pSur-125a decreased the expression of ERBB2/HER2, HDAC5, BIRC5, and SP1, which are hot therapeutic targets for cancer in vitro. Notably, pL-MNP-pSur-125a also downregulated the expression of TDO2 in the human KB cervical carcinoma cells. PL-MNP-pSur-125a decreased the viability of various BIRC5-expressing cancer cells, regardless of the tissue origin or the expression of ABCB1, but not of the human BIRC5-non-expressing HMEC-1 endothelial cells. In vivo, pL-MNP-pSur-125a exhibited potent antitumor growth effects, but without inducing liver toxicity, in various zebrafish human-ABCB1-expressing and ABCB1-non-expressing tumor xenograft models. In conclusion, pL-MNP-pSur-125a is an easy-to-prepare and a promising poly-pharmacological anticancer nanodrug that has the potential to manage numerous malignancies, particularly for patients with BIRC5/ABCB1-related drug resistance after prolonged chemotherapeutic treatments.

Isolation, purification and cytotoxic evaluation of lutein from mixotrophically grown Chlorella sorokiniana TH01

Mixotrophic cultivation of several microalgae simultaneously utilizing two energy sources of light and organic carbon has been reported to significantly achieve higher biomass productivity than phototrophic and heterotrophic modes. In addition, microalgae have been reported as a promising alternative source of marigold for lutein production. In this work, C. sorokiniana TH01 strain was mixotrophically grown on glucose for production of biomass and lutein. Results revealed that algal biomass productivity, lutein content and productivity reached 0.86–2.08 g/L/d, 4.62–6.89 mg/g and 3.98–14.35 mg/L/d, respectively, from 10 g/L glucose, 3 g/L NaNO3 and 2% (v/v) CO2, under light intensity of 50–500 μmol/m2/s and temperature of 27 °C for 10 days of the cultivation. The purification of lutein from the algal biomass was completed by a novel process of simultaneous cell disruption and extraction and silica-based column chromatography purification, reaching lutein purity of 98%. Moreover, the algal lutein can be preserved by solvation with 0.05 wt% ascorbic acid under temperature of <4 °C in the darkness, achieving 90% stability for 120 days of the storage. Chemical structure of the purified algal lutein was fully characterized by NMR and UV–vis spectroscopy and MS spectrometry, showing similar characteristics as the standard lutein and other lutein reported in the literature. Furthermore, the analysis of antiproliferative activity of the algal lutein against human KB, HepG2, MCF-7 and SK-LU-1 cancer cell lines using SRB assay revealed that the algal lutein exhibited moderate activities with corresponding IC50 values determined of 58.07, 61.37, 71.52 and 81.69 μg/mL, respectively. Despite unexpected cytotoxicity on these targeted human cancer cell lines, the algal lutein is a high value compound for commercial applications in food, feed, pharmaceutical and cosmetic industries. The C. sorokiniana TH01 strain was demonstrated to be a promising lutein source, alternatively replacing marigold-based lutein.

High-quantum yield alloy-typed core/shell CdSeZnS/ZnS quantum dots for bio-applications

BackgroundQuantum dots (QDs) have been used as fluorophores in various imaging fields owing to their strong fluorescent intensity, high quantum yield (QY), and narrow emission bandwidth. However, the application of QDs to bio-imaging is limited because the QY of QDs decreases substantially during the surface modification step for bio-application.ResultsIn this study, we fabricated alloy-typed core/shell CdSeZnS/ZnS quantum dots (alloy QDs) that showed higher quantum yield and stability during the surface modification for hydrophilization compared with conventional CdSe/CdS/ZnS multilayer quantum dots (MQDs). The structure of the alloy QDs was confirmed using time-of-flight medium-energy ion scattering spectroscopy. The alloy QDs exhibited strong fluorescence and a high QY of 98.0%. After hydrophilic surface modification, the alloy QDs exhibited a QY of 84.7%, which is 1.5 times higher than that of MQDs. The QY was 77.8% after the alloy QDs were conjugated with folic acid (FA). Alloy QDs and MQDs, after conjugation with FA, were successfully used for targeting human KB cells. The alloy QDs exhibited a stronger fluorescence signal than MQD; these signals were retained in the popliteal lymph node area for 24 h.ConclusionThe alloy QDs maintained a higher QY in hydrophilization for biological applications than MQDs. And also, alloy QDs showed the potential as nanoprobes for highly sensitive bioimaging analysis.Graphical

Synthesis, Cytotoxicity, ADMET and Molecular Docking Studies of Some Quinoline-Pyrimidine Hybrid Compounds: 3-(2-Amino-6-arylpyrimidin-4- yl)-4-hydroxy-1-methylquinolin-2(1H)-ones.

This study aims are the synthesis of 3-(2-amino-6-arylpyrimidin-4-yl)-4-hydroxy-1- methylquinolin-2(1H)-ones and estimation their anticancer activities on HepG2 and KB cancer lines. Many derivatives of quinoline-2-on have been interested to synthesize and evaluate their biological properties by organic chemists due to their various biological effects, including antibacterial, antioxidant, anti-inflammatory, anticancer activities. Quinoline-pyrimidine hybrid compounds exhibited various biological activities, such as antituberculosis, antibacterial, anticancer, antifungal, etc. The connection of 4-hydroxyquinoline-2-one with 2-amino-pyrimidine could initiate the new activities. α,β-Unsaturated ketones of 3-acetyl-4-hydroxy-N-methylquinolin-2-one were prepared. Novel 2-amino-6-aryl-4-(4'-hydroxy-N-methylquinolin-2'-on-3'-yl)pyrimidines have been synthesized by reaction of these corresponding α,β-unsaturated ketones with guanidine hydrochloride. Human hepatocellular carcinoma HepG2 and squamous cell carcinoma KB cancer lines were used for screening their cytotoxicity. 3-Acetyl-4-hydroxy-N-methylquinolin-2-one was prepared from N-methylaniline and diethyl malonate. Reaction of (un)substituted benzaldehydes with this 4-hydroxyquinoline-2-one produced corresponding substituted α,β-unsaturated ketones in the presence of piperidine as catalyst. 2- Amino-6-aryl-4-(4'-hydroxy-N-methylquinolin-2'-on-3'-yl)pyrimidines have been synthesized from these α,β-unsaturated ketones of 3-acetyl-4-hydroxy-N-methylquinolin-2-one by reaction of corresponding α,β-unsaturated ketones with guanidine hydrochloride. All obtained pyrimidines were screened for anticancer activity using MTT bio-assay method. Seven substituted (E)-4-hydroxy-3-(3-(aryl)acryloyl)-1-methylquinolin-2(1H)-ones were prepared and converted to corresponding substituted 2-amino-6-aryl-4-(4'-hydroxy-N-methylquinolin- 2'-on-3'-yl)pyrimidines with yields of 58-74%. All the synthesized pyrimidines were screened for their in vitro anticancer activity against human hepatocellular carcinoma HepG2 and squamous cell carcinoma KB cancer lines. Compounds 6b and 6e had the best activity in the series, with IC50 values equal to 1.32 and 1.33 μM, respectively. ADMET properties showed that compounds 6b, 6e, and 6f possessed the drug-likeness behavior. Cross-docking results indicated that residues GLN778(A), DT8(C), DT9(D), DA12(F), and DG13(F) in the binding pocket as potential ligand binding hot-spot residues for compounds 6b, 6e, and 6f. New substituted 2-amino-6-aryl-4-(4'-hydroxy-N-methylquinolin-2'-on-3'-yl)pyrimidines were obtained and displayed significant inhibition against human hepatocellular carcinoma HepG2 and squamous cell carcinoma KB cancer lines.

Synthesis, Radiolabeling, and Biological Evaluation of 68Ga-Mucin1 and Its Folate Hybrid Peptide Conjugates for the Diagnosis of Ovarian Cancer

Because of our interest in developing new hybrid peptide radioconjugates with suitable biochemical properties for multiple-receptors targeting properties that are overexpressed on many human cancers especially ovarian cancer, we have synthesized 68Ga-NODAGA-MUC1 and 68Ga-NODAGA-MUC1-FA hybrid peptide conjugates using a straightforward and one-step simple reaction. Radiochemical yields were found to be higher than 95% (decay corrected), with a total synthesis time of less than 20 min. Radiochemical purities were always higher than 95% without HPLC purification. In vitro studies on KB cancer cells showed that substantial amounts of the radioconjugates were associated with cell fractions and held great affinities and specificities toward the KB cell line. In vivo characterization in normal female Balb/c mice revealed rapid blood clearance of these radioconjugates with excretion predominantly by the urinary system. Biodistribution studies in nude mice bearing human KB cell line xenografts demonstrated significant tumor uptake and favorable biodistribution profile for 68Ga-NODAGA-MUC1-FA hybrid peptide conjugate compared to the 68Ga-NODAGA-MUC1 peptide monomeric counterpart. The uptake in the tumors was blocked by the excess injection of hybrid peptide, suggesting a receptor-mediated process. These results demonstrate that 68Ga-NODAGA-MUC1-FA hybrid peptide conjugate may be useful as a molecular probe for early detection and staging of folate and MUC1 receptor-positive cancers such as ovarian cancer and their metastasis as well as monitoring tumor response to treatment.