HepG2 Cancer Cell Lines Research Articles

Bioactivities of β-mangostin and its new glycoside derivatives synthesized by enzymatic reactions.

Beta-mangostin is a xanthone commonly found in the genus Garcinia. Unlike α-mangostin, to date, there have only been a few studies on the biological activity and derivatization of β-mangostin. In this study, two novel glycosylated derivatives of β-mangostin were successfully synthesized via a one-pot enzymatic reaction. These derivatives were characterized as β-mangostin 6-O-β-d-glucopyranoside and β-mangostin 6-O-β-d-2-deoxyglucopyranoside by TOF ESI/MS and 1H and 13C NMR analyses. Beta-mangostin showed cytotoxicity against KB, MCF7, A549 and HepG2 cancer cell lines, with IC50 values ranging from 15.42 to 21.13 µM. The acetylcholinesterase and α-glucosidase inhibitory activities of β-mangostin were determined with IC50 values of 2.17 and 27.61 µM, respectively. A strong anti-microbial activity of β-mangostin against Gram-positive strains (Bacillus subtilis, Lactobacillus fermentum and Staphylococcus aureus) was observed, with IC50 values of 0.16, 0.18 and 1.24 µg ml-1, respectively. Beta-mangostin showed weaker activity against Gram-negative strains (Salmonella enterica, Escherichia coli and Pseudomonas aeruginosa) as well as Candida albicans fungus, with IC50 and MIC values greater than the tested concentration (greater than 32 µg ml-1). The new derivatives of β-mangostin showed weaker activities than those of β-mangostin, demonstrating the important role of the hydroxyl group at C-6 of β-mangostin in its bioactivity.

Design of carrageenan based nanocarrier as a drug nanocarrier for tumor targeting: Radiolabeling and biodistribution

Since anti-cancer drugs damage healthy tissues, targeted therapy, especially in cancer treatment, is becoming more important. Thus, many studies have examined delivery systems to mitigate these effects. Carrageenan/poly(N-isopropylacrylamide) (CAR-PNIPAm) based nanocarriers for the delivery of Doxorubicin (DOX) drugs were prepared and characterized in this study. Gamma irradiation was used to create the nanocarriers, while FT-IR, AFM, and DLS were used to characterize them. Particle size was studied in relation to irradiation dose (10–50 kGy) and total polymer content (0.5, 1.0, and 1.5wt%). At pH 5.6 and 7.2, the nanocarrier's DOX-releasing behavior was studied. According to our findings, the smallest particle size (71nm) and zeta potential (−13.2mV) were found in nanocarriers produced with 40kGy and 1wt% of CAR-PNIPAm. The zeta potential shifted to a more stable −30mV after DOX injection. pH was shown to have an effect on the rate at which DOX was released from the nanocarrier. DOX/CAR-PNIPAm nanocarriers efficiently suppressed HepG-2 and MCF-7 cancer cell lines, according to in vitro experiments. In vivo biodistribution experiments were also performed in both normal and solid tumor-bearing mice using a radiolabeled 99mTc-DOX/CAR-PNIPAm nanocarrier. A greater T/NT ratio and cell targeting were seen 30 minutes post-injection in the solid tumour model, demonstrating that the nanocarrier demonstrated tumor targeting potential. In conclusion, our results lend credence to the feasibility of 99mTc-DOX/CAR-PNIPAm nanocarrier for use in therapeutic and diagnostic settings aimed at targeting tumors.

LC-MS/MS-Guided Molecular Networking for Targeted Discovery of Undescribed and Bioactive Ophiobolins from Bipolaris eleusines.

An integrated purification procedure through the LC-MS/MS-based molecular networking strategy combined with bioactive evaluation was first ushered for discovering bioactive ophiobolins from Bipolaris eleusines. Ophiobolins were mainly dispersed in five clusters, which were classified based on different ring systems and functional groups. Nine undescribed ophiobolins (1-6 and 9-11) and an undescribed natural product (8) along with two known analogs (7 and 12) were isolated in target. The undescribed structures were characterized by HR-ESI-MS, NMR spectra, and X-ray diffraction experiments. Compounds 3-12 exhibited strong phytotoxic effects on green foxtails by producing visible lesions, and compounds 1-10 and 12 displayed different levels of cytotoxic activities against cancer cell lines B16, Hep G2, and MCF-7, from which the possible structure-activity relationships were then suggested. The results have supported that bioactivity-guided molecular networking is an efficient strategy to expedite the discovery of undescribed bioactive natural products.

Molecular docking, synthesis and evaluation of the antimicrobial, antiproliferative, and antioxidant properties of β-lactam bisindoles

A series of novel bis(indolyl)methane-β-lactam hybrids has been efficiently synthesized by a [2 + 2]-cycloaddition reaction of imines 5a-c with ketenes derived from substituted acetic acids. All cycloadducts were obtained in good to excellent yields, and their structures were established based on FT-IR, 1H NMR, 13C NMR spectral data, and elemental analysis. The cycloadditions were diastereoselective, leading exclusively to the formation of cis-β-lactams 6a-l. These compounds were evaluated for antibacterial, antioxidant, and antiproliferative activities. All compounds (6a-l) were screened against the gram-positive S. aureus (ATCC 25923) and gram-negative E. coli (ATCC 25922), P. aeruginosa (9027) bacteria. Among the series, compounds 6b-e and 6g-j exhibited significant levels of antibacterial activity, comparable to gentamycin (the control standard). β-Lactams 6a-l were also screened for antiproliferative activities against the MCF-7 and HepG2 cancer cell lines and non-cancerous HEK-293 cell line by MTT assay. Three compounds (6j-k) displayed promising antiproliferative activity against MCF-7. Also, an evaluation of the antioxidant potential of each of the compounds, performed by diphenylpicrylhydrazyl (DPPH) assay, indicated that 6b, 6e-h, and 6j have strong free radical scavenging activity.

Ent-eudesmane sesquiterpenoids from the Chinese liverwort Chiloscyphus polyanthus

− Seven previously undescribed ent-eudesmane sesquiterpenoids (1–7), as well as seven known analogs (8–14), were isolated from the Chinese liverwort Chiloscyphus polyanthus var. rivularis. Their structures were established based on comprehensive spectroscopy analysis, electronic circular dichroism calculations, as well as biosynthetic considerations. The cytotoxicity against HepG2 (Human hepatocellular carcinomas) cancer cell line, and antifungal activity against Candida albicans SC5314 of all isolated ent-eudesmane sesquiterpenoids were preliminarily tested, results showed that the tested compounds did not display obvious cytotoxicity and antifungal activities under the tested concentration.

In vitro and in silico evaluation of new thieno[2,3-d]pyrimidines as anti-cancer agents and apoptosis inducers targeting VEGFR-2

In this study, new thieno[2,3-d]pyrimidine derivatives that could have potential anticancer activity by inhibiting the VEGFR-2 receptor have been designed, synthesized, and investigated. The thieno[2,3-d]pyrimidine derivatives showed strong in vitro abilities to inhibit VEGFR-2 and to prevent cancer cell growth in two different types of cancer cells, MCF-7 and HepG2. Particularly, compound 22 showed the most potent anti-VEGFR-2 activity with an IC50 value of 0.58 µM. Additionally, compound 22 exhibited good anti-proliferative activity against both MCF-7 and HepG2 cancer cell lines, with IC50 values of 11.32 ± 0.32 and 16.66 ± 1.22 µM, respectively. Further investigations revealed that compound 22 induced cell cycle arrest at the G2/M phase and promoted both early and late apoptosis in the MCF-7 cancer cells. Compound 22 also increased the level of BAX (2.8-fold), and reduced the level of Bcl-2 (2.2-fold), hence increasing the rate of apoptosis. Compound 22 also revealed 2.9-fold and 2.8-fold higher levels of caspase-8 and caspase-9, respectively, in the treated MCF-7 cancer cells compared to the control cell lines. The MD simulations showed that the VEGFR-2-22 complex was structurally and energytically stable over 100 ns, while the MM-GBSA study indicated its stable thermodynamic behavior. The bi-dimensional projection analysis confirmed the proper binding of the VEGFR-2-22 complex, while the DFT studies provided optimized geometry, charge distribution, FMO, ESP, the total density of state, and QTAIM maps of compound 22. Finally, computational ADMET studies were performed to assess the drug development potential of the thieno[2,3-d]pyrimidine derivatives. Overall, this study suggests that compound 22 has the potential as an anticancer lead compound by inhibiting VEGFR-2, which may be a guide for future drug design and development.

Finding a Novel Chalcone-Cinnamic Acid Chimeric Compound with Antiproliferative Activity against MCF-7 Cell Line Using a Free-Wilson Type Approach.

In this work, we carried out the design and synthesis of new chimeric compounds from the natural cytotoxic chalcone 2',4'-dihydroxychalcone (2',4'-DHC, A) in combination with cinnamic acids. For this purpose, a descriptive and predictive quantitative structure-activity relationship (QSAR) model was developed to study the chimeric compounds' anti-cancer activities against human breast cancer MCF-7, relying on the presence or absence of structural motifs in the chalcone structure, like in a Free-Wilson approach. For this, we used 207 chalcone derivatives with a great variety of structural modifications over the α and β rings, such as halogens (F, Cl, and Br), heterocyclic rings (piperazine, piperidine, pyridine, etc.), and hydroxyl and methoxy groups. The multilinear equation was obtained by the genetic algorithm technique, using logIC50 as a dependent variable and molecular descriptors (constitutional, topological, functional group count, atom-centered fragments, and molecular properties) as independent variables, with acceptable statistical parameter values (R2 = 86.93, Q2LMO = 82.578, Q2BOOT = 80.436, and Q2EXT = 80.226), which supports the predictive ability of the model. Considering the aromatic and planar nature of the chalcone and cinnamic acid cores, a structural-specific QSAR model was developed by incorporating geometrical descriptors into the previous general QSAR model, again, with acceptable parameters (R2 = 85.554, Q2LMO = 80.534, Q2BOOT = 78.186, and Q2EXT = 79.41). Employing this new QSAR model over the natural parent chalcone 2',4'-DHC (A) and the chimeric compound 2'-hydroxy,4'-cinnamate chalcone (B), the predicted cytotoxic activity was achieved with values of 55.95 and 17.86 µM, respectively. Therefore, to corroborate the predicted cytotoxic activity compounds A and B were synthesized by two- and three-step reactions. The structures were confirmed by 1H and 13C NMR and ESI+MS analysis and further evaluated in vitro against HepG2, Hep3B (liver), A-549 (lung), MCF-7 (breast), and CasKi (cervical) human cancer cell lines. The results showed IC50 values of 11.89, 10.27, 56.75, 14.86, and 29.72 µM, respectively, for the chimeric cinnamate chalcone B. Finally, we employed B as a molecular scaffold for the generation of cinnamate candidates (C-K), which incorporated structural motifs that enhance the cytotoxic activity (pyridine ring, halogens, and methoxy groups) according to our QSAR model. ADME/tox in silico analysis showed that the synthesized compounds A and B, as well as the proposed chalcones C and G, are the best candidates with adequate drug-likeness properties. From all these results, we propose B (as a molecular scaffold) and our two QSAR models as reliable tools for the generation of anti-cancer compounds over the MCF-7 cell line.

New proapoptotic chemotherapeutic agents based on the quinolone-3-carboxamide scaffold acting by VEGFR-2 inhibition

In the current study, we designed and synthesized a series of new quinoline derivatives 10a-p as antiproliferative agents targeting cancer through inhibition of VEGFR-2. Preliminary molecular docking to assess the interactions of the designed derivatives with the binding site of VEGFR-2 (PDB code: 4ASD) displayed binding poses and interactions comparable to sorafenib. The synthesized compounds exhibited VEGFR-2 inhibitory activity with IC50 ranging from 36 nM to 2.23 μM compared to sorafenib (IC50 = 45 nM), where derivative 10i was the most potent. Additionally, the synthesized derivatives were evaluated in vitro for their cytotoxic activity against HepG2 cancer cell line. Seven compounds 10a, 10c, 10d, 10e, 10i, 10n and 10o (IC50 = 4.60, 4.14, 1.07, 0.88, 1.60, 2.88 and 2.76 μM respectively) displayed better antiproliferative activity than sorafenib (IC50 = 8.38 μM). Compound 10i was tested against Transformed Human Liver Epithelial-2 normal cell line (THLE-2) to evaluate its selective cytotoxicity. Furthermore, 10i, as a potent representative of the series, was assayed for its apoptotic activity and cell cycle kinetics’ influence on HepG2, its effects on the gene expression of VEGFR-2, and protein expression of the apoptotic markers Caspase-7 and Bax. Compound 10i proved to have a potential role in apoptosis by causing significant increase in the early and late apoptotic quartiles, a remarkable activity in elevating the relative protein expression of Bax and Caspase-7 and a significant reduction of VEGFR-2 gene expression. Collectively, the obtained results indicate that compound 10i has a promising potential as a lead compound for the development of new anticancer agents.

Enhanced podophyllotoxin production of endophyte Fusarium proliferatum TQN5T by host extract and phenylalanine.

Fermentation technology using endophytes is considered a potential alternative approach for producing pharmaceutical compounds like podophyllotoxin (PTOX). In this study, fungus TQN5T (VCCM 44284) was selected from endophytic fungi isolated from Dysosma versipellis in Vietnam for PTOX production through TLC. The presence of PTOX in TQN5T was further confirmed by HPLC. Molecular identification indicated TQN5T as Fusarium proliferatum with 99.43% identity. This result was asserted by morphological characteristics such as white cottony, filamentous colony, layer and branched mycelium, and clear hyphae septa. Cytotoxic assay indicated both biomass extract and culture filtrate of TQN5T presented strong cytotoxicity on LU-1 and HepG2 with IC50 of 0.11, 0.20, 0.041, and 0071, respectively, implying anti-cancer compounds were accumulated in the mycelium and secreted into the medium. Further, the production of PTOX in TQN5T was investigated in the fermentation condition supplemented with 10µg/ml of host plant extract or phenylalanine as elicitors. The results revealed a significantly higher amount of PTOX in the PDB + PE and PDB + PA at all studied time points in comparison with PDB (control). Especially, after 168h of culture, PTOX content in the PDB with plant extract reached the peak with 314µg/g DW which is 10% higher than the best yield of PTOX in previous studies, denoting F. proliferatum TQN5T as a promising PTOX producer. This is the first study on enhancing the PTOX production in endophytic fungi by supplementing phenylalanine-a precursor for PTOX biosynthesis in plants into fermented media, suggesting a common PTOX biosynthetic pathway between host plant and endophytes. KEY POINTS: • Fusarium proliferatum TQN5T was proven for PTOX production. • Both mycelia extract and spent broth extract of Fusarium proliferatum TQN5T presented strong cytotoxicity on cancer cell lines LU-1 and HepG2. • The supplementation of 10µg/ml host plant extract and phenylalanine into fermentation media of F. proliferatum TQN5T improved the yield of PTOX.

The production of reactive chlorine species (RCS) by argon and helium plasma jets and the sensitivity of liver cancer cell HepG2 to RCS and H2O2 treatment

AbstractThe present study investigated the production of reactive chlorine species (RCS) by Ar/O2 and He/O2 radiofrequency plasma jets in saline solution, and the sensitivity of the liver cancer cell line HepG2 to RCS and H2O2. Both plasma jets were able to produce RCS; however, at similar plasma powers, pressures, and feed gas flow rates, the He/O2 jet was more efficient for RCS production. The lower RCS yield in the case of the Ar/O2 plasma jet was mainly due to the higher RCS quenching. At a low production rate, RCS can be produced in the open air. Viability tests showed that HepG2 cells were more sensitive to H2O2 than RCS.

Steroid Components of Marine-Derived Fungal Strain Penicillium levitum N33.2 and Their Biological Activities

Genus Penicillium comprising the most important and extensively studied fungi has been well-known as a rich source of secondary metabolites. Our study aimed to analyze and investigate biological activities, including in vitro anti-cancer, anti-inflammatory and anti-diabetic properties, of metabolites from a marine-derived fungus belonging to P. levitum. The chemical compounds in the culture broth of P. levitum strain N33.2 were extracted with ethyl acetate. Followingly, chemical analysis of the extract leaded to the isolation of three ergostane-type steroid components, namely cerevisterol (1), ergosterol peroxide (2), and (3β,5α,22E)-ergosta-6,8(14),22-triene-3,5-diol (3). Among these, (3) was the most potent cytotoxic against human cancer cell lines Hep-G2, A549 and MCF-7 with IC50 values of 2.89, 18.51, and 16.47 µg/mL, respectively, while the compound (1) showed no significant effect against tested cancer cells. Anti-inflammatory properties of purified compounds were evaluated based on NO-production in LPS-induced murine RAW264.7 macrophages. As a result, tested compounds performed diverse inhibitory effects on NO production by the macrophages, with the most significant inhibition rate of 81.37 ± 1.35% at 25 µg/mL by the compound (2). Interestingly, compounds (2) and (3) exhibited inhibitory activities against pancreatic lipase and α-glucosidase enzymes in vitro assays. Our study brought out new data concerning the chemical properties and biological activities of isolated steroids from a P. levitum fungus.

Synthesis and Anticancer Activity of Novel Chromene Derivatives, Chromeno[2,3-d][1,3]Oxazines, and Chromeno[2,3-d]Pyrimidines.

Several chromene derivatives have a wide variety of biological and pharmacological activity. They had anticancer activity, antimicrobial activity, antituberculosis activity, anticonvulsant activity, antidiabetic activity, antichlolinesterase activity, and inhibitor of monoamine oxidase activity. The above-mentioned activities directed us to synthesize novel chromene derivatives, chromeno[2,3-d][1,3]oxazines, and chromeno[2,3-d]pyrimidines. The starting material was 2- amino-8-(2-chlorobenzylidene)-4-(2-chlorophenyl)-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile. Several novel chromene derivatives had been synthesized. Compound 1 reacted with carbon disulfide, and ethyl chloroformate to afford chromene derivatives 2, 3. Chromene derivative 3 reacted with hydrazine dydrate to give compound 4. Chromene derivative 1 reacted with acetic acid and sulphuric acid to produce compounds 5, and 6. Amino derivative 5 reacted with chloroacyl derivative to afford compounds 7a-c which cycalized in dry xylene to afford compounds 8a-c. Chromene derivative 8a reacted with hydroxyl amine to afford compound 9. The structures of novel synthesized chromene derivatives had been confirmed using mass spectroscopy, infrared spectroscopy, nuclear magnetic resonance spectroscopy, and elemental analysis. Most of the prepared compounds were screened against liver cancer cell lines (HepG-2), human colon cancer cell lines (HT-29), and breast adenocarcinoma cell lines (MCF-7). Chromene derivative 2 had anticancer activity against human colon cancer cell lines (HT-29) higher than the reference drug doxorubicin. The rest of the tested compounds had anticancer activity against human colon cancer cell lines (HT-29) lower than that of the reference drug doxorubicin. Chromene derivative 5 had anticancer activity against liver cancer cell lines (HepG-2) higher than the reference drug doxorubicin. Several chromene derivatives had been synthesized and their structures had been confirmed using different spectroscopic techniques. Some of the chromene derivatives that were screened against different cancer cell lines showed promising anticancer activity higher than the reference standard drug. For example, chromene derivative 2 had anticancer activity against human colon cancer cell lines (HT-29) higher than the reference drug doxorubicin. Chromene derivative 5 had anticancer activity against liver cancer cell lines (HepG-2) higher than the reference drug doxorubicin. Chromene derivative 6 had anticancer activity against breast adenocarcinoma cell lines (MCF-7) higher than the standard drug.

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.

Novel 5-bromoindole-2-carboxylic Acid Derivatives as EGFR Inhibitors: Synthesis, Docking Study, and Structure Activity Relationship.

The indole backbone is encountered in a class of N-heterocyclic compounds with physiological and pharmacological effects such as anti-cancer, anti-diabetic, and anti-HIV. These compounds are becoming increasingly popular in organic, medicinal, and pharmaceutical research. Nitrogen compounds' hydrogen bonding, dipole- dipole interactions, hydrophobic effects, Van der Waals forces, and stacking interactions have increased their relevance in pharmaceutical chemistry due to their improved solubility. Indole derivatives, such as carbothioamide, oxadiazole, and triazole, have been reported to act as anti-cancer drugs due to their ability to disrupt the mitotic spindle and prevent human cancer cell proliferation, expansion, and invasion. To synthesize new 5-bromoindole-2-carboxylic acid derivatives that function as EGFR tyrosine kinase inhibitors as deduced through molecular docking studies. Different derivatives of indole (carbothioamide, oxadiazole, tetrahydro pyridazine-3,6-dione, and triazole) were synthesized and evaluated through different chemical, spectroscopic methods (IR, 1HNMR, 13CNMR, and MS) and assessed in silico and in vitro for their antiproliferative activities against A549, HepG2, and MCF-7 cancer cell lines. According to molecular docking analyses, compounds 3a, 3b, 3f, and 7 exhibited the strongest EGFR tyrosine kinase domain binding energies. In comparison to erlotinib, which displayed some hepatotoxicity, all of the evaluated ligands displayed good in silico absorption levels, did not appear to be cytochrome P450 inhibitors, and were not hepatotoxic. The new indole derivatives were found to decrease cell growth of three different types of human cancer cell lines (HepG2, A549, and MCF-7), with compound 3a being the most powerful while still being cancer-specific. Cell cycle arrest and the activation of apoptosis were the results of compound 3a's inhibition of EGFR tyrosine kinase activity. The novel indole derivatives, compound 3a in particular, are promising anti-cancer agents which inhibit cell proliferation by inhibiting EGFR tyrosine kinase activity.

Phenolic composition, antioxidant, and cytotoxic effects on HeLa and HepG2 cancer cell lines of Mespilus germanica grown in Turkey

This study screened flavonoids and phenolic acids, antioxidant and cytotoxic effects of Mespilus germanica leaf and fruit samples. The RP-HPLC-DAD analysis allowed the identification of hesperidin, epicatechin, epigallocatechin, benzoic, p-hydroxybenzoic, vanillic, protocatechuic, syringic, caffeic, ferulic, sinapic and p-coumaric acids in various extracts. Fruit alkaline-hydrolysable phenolic acids extract (BHPA), leaf bound phenolic acids from basic hydrolysis-2 extract (BPBH2) and leaf free flavan-3-ol extract exhibited the largest DPPH, OH and NO radicals scavenging activity, respectively. Leaf flavone extract showed strong cytotoxicity on the HepG2 cell line (IC50 = 36.49 ± 1.12 μg/mL) as well as good •OH scavenging and Fe2+ chelation activities. Additionally, leaf bound phenolic acids from acid hydrolysis-1 extract (BPAH1) demonstrated strong cytotoxicity on the HeLa cell line (IC50 = 36.24 ± 1.89 μg/mL). This study suggests Turkish medlar as a natural source of phenolic compounds with potential application in food and pharmaceutical industries as anticancer/antioxidant agents.

Volatile profiling coupled with multivariate analysis, antiproliferative and anti-inflammatory activities of rhizome essential oil of four Hedychium species from India

Ethnopharmacological relevanceThe genus Hedychium of family Zingiberaceae comprises several perennial rhizomatous species widely used in perfumery and traditional folk medicine to treat diseases related to asthma, diarrhoea, nausea, stomach disorders, inflammation and tumours. Several species of Hedychium have remained under-explored with respect to their chemical composition and biological activities. Aim of the studyThe current research aimed to explore the chemical composition and evaluate the antiproliferative and anti-inflammatory activities of rhizome essential oil from four Hedychium species (H. coccineum, H. gardnerianum, H. greenii and H. griffithianum). Materials and methodsCompound identification was accomplished using a Clarus 580 gas chromatography system in conjunction with mass spectrometry (GC-MS). The multivariate data statistics using chemometrics (PCA, PLS-DA, sPLS-DA) and cluster analysis (Dendrogram, Heat maps, K-means) were used to compare the similarity and relationship among Hedychium metabolomes. MTT assay was employed to visualize the antiproliferative property against MCF7, HepG2 and PC3 cancerous cell lines. The toxicity of essential oils was determined using 3T3-L1 non-tumorigenic/normal cells. Lipopolysaccharide (LPS)-induced RAW 264.7 cells were used to investigate the anti-inflammatory properties of Hedychium essential oils by measuring the production of nitric oxide (NO) using the Griess reagent method. Furthermore, the levels of prostaglandin (PGE2) and pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) was assessed using the ELISA technique. ResultsIn total, 82 compounds were identified in four targeted species of Hedychium from which 1,8-cineole (52.71%), β-pinene (32.83%), α-pinene (19.62%), humulene epoxide II (19.86%) and humulene epoxide I (19.10%) were the major constituents. Monoterpenes (8.5–59.9%) and sesquiterpenes (2.87–54.11%) were the two class of compounds, found as the most prevalent in the extracted essential oils. The multivariate analysis classified the four Hedychium species into three different clusters. Hedychium essential oils exhibited potent antiproliferative activity against MCF7, HepG2 and PC3 cancer cell lines with IC50 values less than 150 μg/mL where H. gardnerianum exhibited the highest selective cytotoxicity against human breast and prostate adenocarcinoma cells with an IC50 value of 44.04 ± 1.07 μg/mL and 56.11 ± 1.44 μg/mL, respectively. The essential oils on normal (3T3-L1) cells displayed no toxicity with higher IC50 values thereby concluding as safe to use for normal human health without causing any side effects. Besides, the essential oils at 100 μg/mL concentration revealed remarkable anti-inflammatory activity in LPS-activated RAW 264.7 murine macrophages by inhibiting the production of inflammatory mediators, with H. greenii exhibiting the maximum anti-inflammation response by significantly suppressing the levels of NO (84%), PGE2 (87%), TNF-α (94.3%), IL-6 (95%) and IL-1β (85%) as compared to LPS treated group. ConclusionThe present findings revealed that the Hedychium species traditionally used in therapeutics could be a potential source of active compounds with antiproliferative and anti-inflammatory properties.

Licochalcone A Derivatives as Selective Dipeptidyl Peptidase 4 Inhibitors with Anti-Inflammatory Effects.

A set of 22 analogs of licochalcone A was designed and synthesized to explore their potentials as dipeptidyl peptidase 4 (DPP4) inhibitors with anti-inflammatory effects. The anti-DPP4 effects of these analogs were evaluated using the fluorescent substrate Gly-Pro-N-butyl-4-amino-1,8-naphthalimide (GP-BAN). The nitro-substituted analogue 27 exhibited the most potent activity (Ki = 0.96 μM). A structure-activity relationship investigation revealed that 4-hydroxyl and 5-chloro substituents are essential for DPP4 inhibition, while the 3'-nitro substituent improved both DPP4 inhibition and microsomal stability. Furthermore, compound 27 demonstrated good selectivity for DPP4 over other proteases, including dipeptidyl peptidase 9 (DPP9), thrombin, prolyl endopeptidase (PREP), and fibroblast activation protein (FAP). The cytotoxic effect of 27 was evaluated in cancer cell lines HepG-2 and Caco-2 and in somatic RAW264.7 cells and RPTECs. Compound 27 showed no toxicity to normal cells and weak toxicity to cancer cells. In a living cell imaging assay, 27 blocked the dipeptidase activity of DPP4 in both Caco-2 and HepG-2 cells. This compound also dose-dependently suppressed the expression levels of the chemokines tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β).

Cytotoxic effects of aporphine alkaloids from the stems and leaves of Stephania dielsiana Y.C.Wu

Phytochemical studies of the stems and leaves of Stephania dielsiana Y.C.Wu yielded two new aporphine alkaloids (1 and 5), along with six known alkaloids (2–4 and 6–8). Their structures were characterised based on analyses of spectroscopic data, including one- and two-dimensional nuclear magnetic resonance (NMR) spectroscopy and high-resolution electrospray ionisation mass spectrometry (HR-ESI-MS). The cytotoxic activities of the isolated compounds against a small panel of tumour cell lines were assessed by MTS assay. Interestingly, compound 2 exhibited particularly strong cytotoxic activities against HepG2, MCF7 and OVCAR8 cancer cell lines, with IC50 values of 3.20 ± 0.18, 3.10 ± 0.06 and 3.40 ± 0.007 µM, respectively. Furthermore, molecular docking simulations were carried out to explore the interactions and binding mechanisms of the most active compound (compound 2) with proteins. Our results contribute to understanding the secondary metabolites produced by S. dielsiana and provide a scientific rationale for further investigations of cytotoxicity of this valuable medicinal plant.

K-Carrageenan based magnetic@polyelectrolyte complex composite hydrogel for pH and temperature-responsive curcumin delivery

The dual stimuli-responsive drug delivery system has attracted a lot of interest in controlled drug delivery to specific sites. The magnetic iron oxide nanoparticles integrated polyelectrolyte complex-based hydrogel (MPEC HG) system was developed in this work. First, magnetic nanoparticles were produced in situ in the synthetic polymer polyhexamethylene guanidine (PHMG). Furthermore, the natural biopolymer k-carrageenan (kCG) was employed to form the polyelectrolyte complex (PEC) through charge-balancing interaction between positively charged guanidine units and negatively charged sulfonate groups. Various characterization approaches were used to characterize the developed magnetic polyelectrolyte complex hydrogel (MPEC HG) system. Curcumin (Cur) was employed as a model bioactive agent to examine the drug loading and stimuli-responsive drug release efficiency of the MPEC HG system. Under the combined pH and temperature stimuli conditions (pH 5.0/42 °C), the developed hydrogel system demonstrated great drug loading efficiency (∼ 68 %) and enhanced drug release. Furthermore, the MPEC HG system's in vitro cytotoxicity behavior was investigated on a human liver cancer (HepG2) cell line, and the results revealed that the MPEC HG system is biocompatible. As a result, the MPEC HG system might be used for dual pH and temperature stimuli-responsive drug delivery applications in cancer therapy.

Design, synthesis, molecular docking and biological evaluation of new carbazole derivatives as anticancer, and antioxidant agents

BackgroundThe carbazole skeleton is an important structural motif occurring naturally or synthesized chemically and has antihistaminic, antioxidant, antitumor, antimicrobial, and anti-inflammatory activities.ObjectivesThis study aimed to design and synthesize a novel series of carbazole derivatives and evaluate their antiproliferative and antioxidant activities.MethodsThe synthesized compounds were characterized utilizing HRMS, 1H-, and 13CAPT-NMR, and assessed for their anticancer, antifibrotic, and antioxidant effects utilizing reference biomedical procedures. In addition, the AutoDock Vina application was used to perform in-silico docking computations.ResultsA series of carbazole derivatives were synthesized and characterized in the current study. Compounds 10 and 11 were found to have a stronger antiproliferative effect than compounds 2–5 against HepG2, HeLa, and MCF7 cancer cell lines with IC50 values of 7.68, 10.09, and 6.44 µM, respectively. Moreover, compound 9 showed potent antiproliferative activity against HeLa cancer cell lines with an IC50 value of 7.59 µM. However, except for compound 5, all of the synthesized compounds showed moderate antiproliferative activities against CaCo-2 with IC50 values in the range of 43.7–187.23 µM. All of these values were compared with the positive control anticancer drug 5-Fluorouracil (5-FU). In addition, compound 9 showed the most potent anti-fibrotic compound, and the cellular viability of LX-2 was found 57.96% at 1 µM concentration in comparison with the positive control 5-FU. Moreover, 4 and 9 compounds showed potent antioxidant activities with IC50 values of 1.05 ± 0.77 and 5.15 ± 1.01 µM, respectively.ConclusionMost of the synthesized carbazole derivatives showed promising antiproliferative, antioxidant, and antifibrotic biological effects, and further in-vivo investigations are needed to approve or disapprove these results.