Synthesis, Anticancer Activity, and Molecular Docking of New 1,2,3-Triazole Linked Tetrahydrocurcumin Derivatives.

Cancer is one of the deadliest diseases to humanity. There is significant progress in treating this disease, but developing some drugs that can fight this disease remains a challenge in the field of medical research. Thirteen new 1,2,3-triazole linked tetrahydrocurcumin derivatives were synthesized by click reaction, including a 1,3-dipolar cycloaddition reaction of tetrahydrocurcumin baring mono-alkyne with azides in good yields, and their in vitro anticancer activity against four cancer cell lines, including human cervical carcinoma (HeLa), human lung adenocarcinoma (A549), human hepatoma carcinoma (HepG2), and human colon carcinoma (HCT-116) were investigated using MTT(3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetraz-olium bromide) assay. The newly synthesized compounds had their structures identified using NMR HRMS and IR techniques. Some of prepared compounds, including compounds 4g and 4k, showed potent cytotoxic activity against four cancer cell lines compared to the positive control of cisplatin and tetrahydrocurcumin. Compound 4g exhibited anticancer activity with a IC50 value of 1.09 ± 0.17 µM against human colon carcinoma HCT-116 and 45.16 ± 0.92 µM against A549 cell lines compared to the positive controls of tetrahydrocurcumin and cisplatin. Moreover, further biological examination in HCT-116 cells showed that compound 4g can arrest the cell cycle at the G1 phase. A docking study revealed that the potential mechanism by which 4g exerts its anti-colon cancer effect may be through inhabiting the binding of APC-Asef. Compound 4g can be used as a promising lead for further exploration of potential anticancer agents.

Engineering of the Central Core on DBD-Based Materials with Improved Power-Conversion Efficiency by Using the DFT Approach.

Developing proficient organic solar cells with improved optoelectronic properties is still a matter of concern. In the current study, with an aspiration to boost the optoelectronic properties and proficiency of organic solar cells, seven new small-molecule acceptors (Db1-Db7) are presented by altering the central core of the reference molecule (DBD-4F). The optoelectronic aspects of DBD-4F and Db1-Db7 molecules were explored using the density functional theory (DFT) approach, and solvent-state calculations were assessed utilizing TD-SCF simulations. It was noted that improvement in photovoltaic features was achieved by designing these molecules. The results revealed a bathochromic shift in absorption maxima (λmax) of designed molecules reaching up to 776 nm compared to 736 nm of DBD-4F. Similarly, a narrow band gap, low excitation energy, and reduced binding energy were also observed in newly developed molecules in comparison with the pre-existing DBD-4F molecule. Performance improvement can be indicated by the high light-harvesting efficiency (LHE) of designed molecules (ranging from 0.9992 to 0.9996 eV) compared to the reference having a 0.9991 eV LHE. Db4 and Db5 exhibited surprisingly improved open-circuit voltage (V OC) values up to 1.64 and 1.67 eV and a fill factor of 0.9198 and 0.9210, respectively. Consequently, these newly designed molecules can be considered in the future for practical use in manufacturing OSCs with improved optoelectronic and photovoltaic attributes.

Functional and financial analysis of an inclined step solar desalination using phase change nanomaterials.

Recent decades have seen a shortage of water, which has led scientists to concentrate on solar desalination technologies. The present study examines the solar water desalination system with inclined steps, while considering various phase change materials (PCMs). The findings suggest that the incorporation of PCM generally enhances the productivity of the solar desalination system. Additionally, the combination of nanoparticles has been used to PCM, which is a popular technique utilized nowadays to improve the efficiency of these systems. The current investigation involves the transient modeling of a solar water desalination system, utilizing energy conservation equations. The equations were solved using the Runge-Kutta technique of the ODE23s order. The temperatures of the salt water, the absorbent plate of the glass cover, and the PCM were calculated at each time. Without a phase changer, the rate at which fresh water is produced is around 5.15 kg/m2·h. The corresponding mass flow rates of paraffin, n-PCM I, n-PCM III, n-PCM II, and stearic acid are 22.9, 28.9, 5.9, 11.9, and 73 kg/m2·h. PCMs, with the exception of stearic acid, exhibit similar energy efficiency up to an ambient temperature of around 29°. However, at temperatures over 29°, n-PCM II outperforms other PCM.

Synthesis and evaluation of pentacyclic triterpenoids conjugates as novel HBV entry inhibitors targeting NTCP receptor.

Chronic liver diseases caused by hepatitis B virus (HBV) are the accepted main cause leading to liver cirrhosis, hepatic fibrosis, and hepatic carcinoma. Sodium taurocholate cotransporting polypeptide (NTCP), a specific membrane receptor of hepatocytes for triggering HBV infection, is a promising target against HBV entry. In this study, pentacyclic triterpenoids (PTs) including glycyrrhetinic acid (GA), oleanolic acid (OA), ursolic acid (UA) and betulinic acid (BA) were modified via molecular hybridization with podophyllotoxin respectively, and resulted in thirty-two novel conjugates. The anti-HBV activities of conjugates were evaluated in HepG2.2.15 cells. The results showed that 66% of the conjugates exhibited lower toxicity to the host cells and had significant inhibitory effects on the two HBV antigens, especially HBsAg. Notably, the compounds BA-PPT1, BA-PPT3, BA-PPT4, and UA-PPT3 not only inhibited the secretion of HBsAg but also suppressed HBV DNA replication. A significant difference in the binding of active conjugates to NTCP compared to the HBV PreS1 antigen was observed by SPR assays. The mechanism of action was found to be the competitive binding of these compounds to the NTCP 157-165 epitopes, blocking HBV entry into host cells. Molecular docking results indicated that BA-PPT3 interacted with the amino acid residues of the target protein mainly through π-cation, hydrogen bond and hydrophobic interaction, suggesting its potential as a promising HBV entry inhibitor targeting the NTCP receptor.

Dual targetable drug delivery system based on cell membrane camouflaged liposome for enhanced tumor targeting and improved anti-tumor efficiency.

Receptor and ligand binding mediated targeted drug delivery systems (DDS) sometimes fail to target to tumor sites, and cancer cell membrane (CCM) coating can overcome the dilemma of immune clearance and nonspecific binding of DDS in vivo. In order to enhance the targeting ability and improve the anti-tumor effect, a dual targeting DDS was established based on U87MG CCM mediated homologous targeting and cyclic peptide RGD mediated active targeting. The DDS was prepared by coating RGD doped CCM onto doxorubicin (DOX) loaded liposomes. The homologous and active dual targeting ability endowed the DDS (RGD-CCM-LP-DOX) exhibited superior cancer cell affinity, improved tissue distribution and enhanced anti-tumor effects. In vivo pharmacodynamic studies revealed that RGD-CCM-LP-DOX exhibited superior therapeutic effect compared with homologous targeting CCM-LP-DOX and non-targetable LP-DOX injection. H&E staining, Ki 67 staining and TUNEL staining confirmed that RGD-CCM-LP-DOX not only increased anti-tumor efficacy, but also reduced tissue toxicity by changing the distribution in vivo. The experimental results showed that the RGD doped CCM camouflaged liposome DDS is a better choice for chemotherapeutics delivery.

A systematic review on Nb2O5-based photocatalysts: Crystallography, synthetic methods, design strategies, and photocatalytic mechanisms.

With the increasing popularity of photocatalytic technology and the highly growing issues of energy scarcity and environmental pollution, there is an increasing interest in extremely efficient photocatalytic systems. The widespread immense attention and applicability of Nb2O5 photocatalysts can be attributed to their multiple benefits, including strong redox potentials, non-toxicity, earth abundance, corrosion resistance, and efficient thermal and chemical stability. However, the large-scale application of Nb2O5 is currently impeded by the barriers of rapid recombination loss of photo-activated electron/hole pairs and the inadequacy of visible light absorption. To overcome these constraints, plentiful design strategies have been directed at modulating the morphology, electronic band structure, and optical properties of Nb2O5. The current review offers an extensive analysis of Nb2O5-based photocatalysts, with a particular emphasis on crystallography, synthetic methods, design strategies, and photocatalytic mechanisms. Finally, an outline of future research directions and challenges in developing Nb2O5-based materials with excellent photocatalytic performance is presented.

Synthesis and antitumor activity of new tetrahydrocurcumin derivatives via click reaction.

Three new derivatives of tetrahydrocurcumin 6, 7 and 9 have been prepared as potent antitumor agents using copper(II)-catalyzed 'click chemistry'. Their structures were identified using 1H-NMR, 13C-NMR and HRMS techniques. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay has been carried out to investigate the in vitro cytotoxicity against human cervical carcinoma (HeLa), human lung adenocarcinoma (A549), human hepatoma carcinoma (HepG2) and human colon carcinoma (HCT-116). Compound 6 has showed significant inhibitory activity against HCT-116 cell line with an IC50 value of 17.86 µM compared to tetrahydrocurcumin (50.96 µM) and positive control etoposide (19.48 µM) while showed no inhibitory activity against NCM460 cell line. Compounds 7 showed moderate inhibitory activity compared to tetrahydrocurcumin and etoposide while compound 9 showed no obvious inhibitory activity. The results suggested further structure modifications of tetrahydrocurcumin to improve its anticancer activity.[Formula: see text].

Cinnamaldehyde Improves Metabolic Functions in Streptozotocin-Induced Diabetic Mice by Regulating Gut Microbiota.

PURPOSE: The aim of the present study was to examine the protective effects of cinnamaldehyde (CA) on type 1 diabetes mellitus (T1DM) and explore the underlying molecular mechanisms by using multiple omics technology. METHODS: T1DM was induced by streptozotocin in the mice. Immunostaining was performed to evaluate glycogen synthesis in the liver and morphological changes in the heart. Gut microbiota was analyzed using 16S rRNA gene amplification sequencing. The serum metabolomics were determined by liquid chromatography-mass spectrometry. The relevant gene expression levels were determined by quantitative real-time PCR. RESULTS: CA treatment significantly improved the glucose metabolism and insulin sensitivity in T1DM mice. CA increased glycogen synthesis in the liver and protected myocardial injury in T1DM mice. CA affected the gut microbiota particularly by increasing the relative abundance of Lactobacillus johnsonii and decreasing the relative abundance of Lactobacillus murinus in T1DM mice. The glucose level was positively correlated with 88 functional pathways of gut microbiota and negatively correlated with 2 functional pathways of gut microbiota. Insulin resistance was positively correlated with 11 functional pathways. The analysis of serum metabolomics showed that CA treatment significantly increased the levels of taurochenodeoxycholic acid, tauroursodeoxycholic acid, tauro-α-muricholic acid and tauro-ß-muricholic acid, taurodeoxycholic acid, taurocholic acid and taurohyodeoxycholic acid in T1DM mice. Taurohyodeoxycholic acid level was highly correlated with the blood glucose levels. Furthermore, the abundance of Faecalibacterium prausnitzii was positively correlated with AKT2, insulin like growth factor 1 receptor, E2F1 and insulin receptor substrate 1 mRNA expression levels, while taurohyodeoxycholic acid level was negatively correlated with IRS1 mRNA expression level. CONCLUSION: Our results indicated that CA may interfere with gut microbiota to affect host metabolomics, especially the bile acids, so as to directly or indirectly modulate the expression levels of glucose metabolism-related genes, thus subsequently reducing the blood glucose level in the T1DM mice.

Recent progress in chemical approaches for the development of novel neuraminidase inhibitors.

Influenza virus is the main cause of an infectious disease called influenza affecting the respiratory system including the throat, nose and lungs. Neuraminidase inhibitors are reagents used to block the enzyme called neuraminidase to prevent the influenza infection from spreading. Neuraminidase inhibitors are widely used in the treatment of influenza infection, but still there is a need to develop more potent agents for the more effective treatment of influenza. Complications of the influenza disease lead to death, and one of these complications is drug resistance; hence, there is an urgent need to develop more effective agents. This review focuses on the recent advances in chemical synthesis pathways used for the development of new neuraminidase agents along with the medicinal aspects of chemically modified molecules, including the structure-activity relationship, which provides further rational designs of more active small molecules.