Synthesis, anticancer evaluation of novel hybrid pyrazole-based chalcones, molecular docking, DNA fragmentation, and gene expression: in vitro studies.

A unique series of pyrazolyl-chalcone derivatives was synthesized via the method of Claisen-Schmidt condensation. The desired chalcone derivatives 7a-d and 9a-f were obtained in good yields by reacting the 4-acetyl-5-thiophene-pyrazole with the appropriate heteroaryl aldehyde derivatives. The novel chalcones have undergone complete elemental analysis, 1H-NMR, 13C-NMR, mass spectrometry, and IR characterization. The three human cancer cell lines MCF7 (human Caucasian breast adenocarcinoma), PC3 (prostatic cancer) and PACA2 (pancreatic carcinoma) as well as the normal cell line BJ1 (normal skin fibroblasts) were tested in vitro for the anti-cancer properties of the newly synthesized chalcone derivatives. When compared to the reference medicine doxorubicin (IC50 = 52.1 µM), compound 9e showed the most promise derivative (IC50 = 27.6 µM) against PACA2 cells, while compound 7d demonstrated anticancer efficacy (IC50 = 42.6 µM against MCF7 cells compared to the reference drug doxorubicin (IC50 = 48 µM). Using breast and pancreatic cell lines, the gene expression, DNA damage, and DNA fragmentation percentages for compounds 7d and 9e were evaluated. Moreover, the molecular docking study of compounds 7d and 9e was assessed. The binding affinities of compound 9e toward P53 mutant Y220C was -22 kcal per mole, while those of compound 7d towards Bcl2 and CDK4 were -27.81 and -26.9 kcal per mole, respectively, compared to the standard values (-15.82, -33.96 and -29.9 kcal per mole).

Synthesis, cytotoxicity, anti-inflammatory, anti-metastatic and anti-oxidant activities of novel chalcones incorporating 2-phenoxy-N-arylacetamide and thiophene moieties: induction of apoptosis in MCF7 and HEP2 cells.

Eight Novel chalcones were synthesized and their structures were confirmed by different spectral tools. All the prepared compounds were subjected to SRB cytotoxic screening against several cancer cell lines. Compound 5c exerted the most promising effect against MCF7 and HEP2 cells with IC50 values of 9.5 and 12 µg/mL, respectively. Real-time PCR demonstrated the inhibitory effect of compound 5c on the expression level of Antigen kiel 67 (KI-67), Survivin, Interleukin-1beta (IL-1B), Interleukin-6 (IL-6), Cyclooxygenase-2 (COX-2) and Protein kinase B (AKT1) genes. Flow-cytometric analysis of the cell cycle indicated that compound 5c stopped the cell cycle at the G0/G1 and G2/M phases in MCF7 and HEP2 treated cells, respectively. ELISA assay showed that Caspase 8, Caspase 9, P53, BAX, and Glutathione (GSH) were extremely activated and Matrix metalloproteinase 2 (MMP2), Matrix metalloproteinase 9 (MMP9), BCL2, Malondialdehyde (MDA), and IL-6 were deactivated in 5c treated MCF7 and HEP2 cells. Wound healing revealed that chalcone 5c reduced the ability to close the scrape wound and decreased the number of migrating MCF7 and HEP2 cells compared to the untreated cells after 48 h. Theoretical molecular modeling against P53 cancer mutant Y220C and Bcl2 showed binding energies of -22.8 and -24.2 Kcal/mole, respectively, which confirmed our ELISA results.

Synthesis of novel chitosan-Schiff bases nanoparticles for high efficiency Helicobacter pylori inhibition.

Two chitosan Schiff bases were synthesized by condensation of chitosan with 2-(4-formylphenoxy)-N-phenylacetamide and N-(4-bromophenyl)-2-(4-formylphenoxy) acetamide denoted as Cs-SBA and Cs-SBBr, respectively. The molecular structures of the resulting chitosan derivatives were characterized using FTIR and 1HNMR and their thermal properties were investigated by TGA. These derivatives were treated with sodium tripolyphosphate (TPP) to produce Cs Schiff base nanoparticles. The nanoparticles physicochemical properties were determined by FTIR, XRD, TEM, and zeta potential analysis. The antimicrobial action against Helicobacter pylori (H. pylori) was evaluated and the results indicated that the anti-H. pylori activity had minimal inhibitory concentration MIC values of 15.62 ± 0.05 and 3.9 ± 0.03 µg/mL for Cs-SBA and Cs-SBBr nanoparticles (Cs-SBA NPs and Cs-SBBr NPs), respectively. The better biologically active nanoparticles, Cs-SBBr NPs, were tested for their cyclooxygenases (COX-1 and COX-2) inhibitory potential. Cs-SBBr NPs demonstrated COX enzyme inhibition activity against COX-2 (IC50 4.5 ± 0.165 µg/mL) higher than the conventional Indomethacin (IC50 0.08 ± 0.003 µg/mL), and Celecoxib (IC50 0.79 ± 0.029 µg/mL). Additionally, the cytotoxicity test of Cs-SBBr NPs showed cytotoxic effect on Vero cells (CCL-81) with IC50 = 17.95 ± 0.12 µg/mL which is regarded as a safe compound. Therefore, Cs-SBBr NPs may become an alternative to cure H. pylori and prevent gastric cancer.

Novel hybrid thiazoles, bis-thiazoles linked to azo-sulfamethoxazole: Synthesis, docking, and antimicrobial activity.

The reaction of sulfamethoxazolehydrazonoyl chloride with thiosemicarbazones, bis-thiosemicarbazones, or 4-amino-3-mercapto-1,2,4-triazole in dioxane in the presence of triethylamine as a basic catalyst at reflux resulted in the regioselective synthesis of thiazoles and bis-thiazoles linked to azo-sulfamethoxazole as novel hybrid molecules. The structures of the new compounds were confirmed using a range of spectra. Each compound's antibacterial properties were evaluated using the agar well-diffusion technique, and most of them demonstrated significant potency. In silico investigations revealed that the described compounds had strong interactions with the binding sites of MurE ligase, tyrosyl-tRNA synthetase, and dihydropteroate synthase, demonstrating inhibitory activity.

Utility of 2-Chloro-N-arylacetamide and 1,1'-(Piperazine-1,4-diyl)bis(2-chloroethanone) as Versatile Precursors for Novel Mono- and Bis[thienopyridines].

A series of novel thieno[2,3-b]pyridines linked to N-aryl carboxamides or (carbonylphenoxy)-N-(aryl)acetamides, as well as bis(thieno[2,3-b]pyridines) linked to piperazine core via methanone or carbonylphenoxyethanone units, were synthesized by treating the appropriate chloroacetyl- or bis-bromoacetyl derivatives with 2-mercaptonicotinonitrile derivatives in ethanolic sodium ethoxide at reflux. The spectral data were used to determine the compositions of novel compounds.

Anticancer behaviour of 2,2'-(pyridin-2-ylmethylene)bis(5,5-dimethylcyclohexane-1,3-dione)-based palladium(II) complex and its DNA, BSA binding propensity and DFT study.

Herein, we report the synthesis and biological evaluation of [Pd(L)(OH2)Cl] complex (where L = 2,2'-(pyridin-2-ylmethylene)bis(5,5-dimethylcyclohexane-1,3-dione) as a novel promising anticancer candidate. The complex was characterized by single-crystal X-ray diffraction and other various spectroscopic techniques. Besides, the optimized structure was determined through DFT calculations revealing that the coordination geometry of [Pd(L)(OH2)Cl] complex is square planar. The binding propensity of [Pd(L)(OH2)Cl] complex with DNA and BSA was assessed by the spectrophotometric method. The antimicrobial profile of the ligand and its [Pd(L)(OH2)Cl] complex was screened against clinically important bacterial strains. [Pd(L)(OH2)Cl] complex showed promising activity against these microorganisms. Pd(L)(OH2)Cl] complex exhibited a potent antiproliferative potential compared to its ligand against different human cancer cells (A549, HCT116, MDA-MB-231, and HepG2) with less toxic effect against normal cells (WI-38). Additionally, [Pd(L)(OH2)Cl] complex exerted its anticancer effects against the most responsive cells (HCT116 cells; IC50 = 11 ± 1 µM) through suppressing their colony-forming capabilities and triggering apoptosis and cell cycle arrest at S phase. Quantitative PCR analysis revealed a remarkable upregulation of the mRNA expression level of p53 and caspase-3 by 4.8- and 5.9-fold, respectively, relative to control. Remarkable binding properties and non-covalent interactions between L and its [Pd(L)(OH2)Cl] complex with the binding sites of different receptors including CDK2, MurE ligase, DNA, and BSA were established using molecular docking. Based on our results, [Pd(L)(OH2)Cl] complex is an intriguing candidate for future investigations as a potential anticancer drug for the treatment of colon cancer.

Novel Bis(2-cyanoacrylamide) Linked to Sulphamethoxazole: Synthesis, DNA Interaction, Anticancer, ADMET, Molecular Docking, and DFT Studies.

In the light of advancement and potential extensive use of medication design and therapy, new bis(cyanoacrylamides) incorporating sulphamethoxazole derivatives (7 a-7 f) were synthesized and confirmed by different spectral tools. In vitro anticancer activity towards different human cancer cells (HCT116, MDA-MB-231 and A549) was assessed using MTT assay. Among all derivatives, 4C- and 6C-spacer derivatives (7 e and 7 f) had the most potent growth inhibitory activities against HCT116 cells with IC50 values of 39.7 and 28.5 µM, respectively. 7 e and 7 f induced apoptosis and suppressed migration of HCT116 cells. These compounds also induced a significant increase in caspase-3 and CDH1 activities, and a downregulation of Bcl2 using ELISA. pBR322 DNA cleavage activities of cyanoacrylamides were determined using agarose gel electrophoresis. Furthermore, 7 e and 7 f showed good DNA and BSA binding affinities using different spectroscopic techniques. Furthermore, molecular docking for 7 e and 7 f was performed to anticipate their binding capabilities toward various proteins (Bcl2, CDH1 and BSA). The docking results were well correlated with those of experimental results. Additionally, density functional theory and ADMET study were performed to evaluate the molecular and pharmacokinetic features of 7 e and 7 f, respectively. Thus, this work reveals promising antitumor lead compounds that merit future research and activity enhancement.

Novel cyanochalcones as potential anticancer agents: apoptosis, cell cycle arrest, DNA binding, and molecular docking studies.

In the light of anticancer drug discovery and development, a new series of cyanochalcones incorporating indole moiety (5a-g) were efficiently synthesized and characterized by different spectral analysis. MTT assay was used to evaluate the antiproliferative activity of the synthesized compounds towards different cancer cells (Hela, MDA-MB-231, A375, and A549) in parallel with normal cells (HSF). Trimethoxy and diethoxy-containing derivatives (5d and 5e) displayed the most selective cytotoxic activities against cervical Hela cells with IC50 values of 8.29 and 11.82 µM, respectively, with great safety pattern toward normal HSF cells (Selectivity index: 21.3 and 13.9, respectively). Therefore, 5d and 5e were chosen to study their effects on apoptosis, cell cycle arrest, and migration of Hela cells using flow cytometric analysis and wound healing assay. They induced apoptosis and cell cycle arrest at the S phase and impaired migration of HeLa cells. Regarding their effects on the expression profile of crucial genes related to the potential anticancer activities, 5d and 5e remarkably upregulated caspase 3 and Beclin1 and downregulated cyclin A1, CDK2, CDH2, MMP9, and HIF1A using qRT-PCR and ELISA techniques. UV-Vis spectral measurement demonstrated the ability of 5d and 5e to bind CT-DNA efficiently with Kb values of 3.7 × 105 and 1 × 105 M-1, respectively. Moreover, in silico molecular docking was performed to assess the binding affinities of the compounds toward the active sites of Bcl2, CDK2, and DNA. Therefore, cyanochalcones 5d and 5e might be promising anticancer agents and could offer a scientific basis for intensive research into cancer chemotherapy.Communicated by Ramaswamy H. Sarma.

A novel series of cyanochalcones incorporating indole moiety (5a­g) were designed and synthesized.Cytotoxic activities of the designed compounds were evaluated in vitro against different human cancer cell lines (Hela, MDA-MB-231, A375, and A549) in parallel with human normal cells (HSF).5d and 5e stimulated apoptosis (through deregulating Bcl2 and upregulating Cas3), cell cycle arrest at the S phase (by suppressing cyclin A and CDK2), and inhibited migration (through downregulating CDH2 and MMP9) of Hela cells.5d and 5e demonstrated good DNA binding affinities.Molecular docking was carried out to confirm the binding abilities of 5d and 5e toward Bcl2, CDK2, and DNA.

Synthesis of Novel Diphenyl Ether-Based Bis-Heterocycles as Novel Hybrid Molecules via Michael and Other Cyclocondensation Reactions.

Molecular hybridization is a technique used in drug creation that involves combining the pharmacophoric moieties of multiple bioactive compounds to create a new hybrid molecule with better affinity and effectiveness. In this regard, we created unique hybrid molecules out of diphenyl ether-linked fused pyrans and other heterocycles. The Michael reaction of 4,4'-oxydibenzaldehyde with malononitrile and various active methylene derivatives, as well as enaminone derivatives, produced the matching bis-fused pyrans and fused pyridines, both connected to a diphenyl ether moiety. Furthermore, the acid-catalyzed reaction of 4,4'-oxydibenzaldehyde with dimedone or ß-naphthol produced the corresponding new bis(hexahydro-1H-xanthene-1,8-dione) and bis(14H-dibenzo[a,j]xanthene). The processes by which the target products are formed were also examined.

Novel 3-(pyrazol-4-yl)-2-(1H-indole-3-carbonyl)acrylonitrile derivatives induce intrinsic and extrinsic apoptotic death mediated P53 in HCT116 colon carcinoma.

A novel series of α-cyano indolylchalcones was prepared, and their chemical structures were confirmed based on the different spectral data. Among them, compound 7f was observed to be the most effective bioactive chalcone with distinguished potency and selectivity against colorectal carcinoma (HCT116) with IC50 value (6.76 µg/mL) relative to the positive control (5 FU) (77.15 µg/mL). In a preliminary action study, the acrylonitrile chalcone 7f was found to enhance apoptotic action via different mechanisms like inhibition of some anti-apoptotic protein expression, regulation of some apoptotic proteins, production of caspases, and cell cycle arrest. All mechanisms suggested that compound 7f could act as a professional chemotherapeutic agent. Also, a molecular docking study was achieved on some selected proteins implicated in cancer (Caspase 9, XIAP, P53 mutant Y220C, and MDM2) which showed variable interactions with compound 7f with good Gibbs free energy scores.

Novel Scaffolds Based on Bis-thiazole Connected to Quinoxaline or Thienothiophene through 2-Phenoxy-N-arylacetamide Groups as New Hybrid Molecules: Synthesis, Antibacterial Activity, and Molecular Docking Investigations.

The resistance of microorganisms to antimicrobials has endangered the health of many people across the world. Overcoming the resistance problem will require the invention of molecules with a new mechanism of action so that no cross-resistance with existing therapies occurs. Because of their powerful antibacterial activity against a wide spectrum of Gram-positive and Gram-negative bacterial strains, heterocyclic compounds are appealing candidates for medicinal chemists. In this regard, as unique hybrid compounds, we synthesized a novel family of bis-thiazoles linked to quinoxaline or thienothiophene via the 2-phenoxy-N-arylacetamide moiety. The target compounds were synthesized by reacting the relevant bis(α-haloketones) with the corresponding thiosemicarbazones in EtOH at reflux with a few drops of TEA. Under comparable reaction conditions, the isomeric bis(thiazoles) were synthesized by reacting the appropriate bis(thiosemicarbazone) with the respective α-haloketones. The structures of the novel compounds were confirmed using elements and spectral data. All of the synthesized compounds were tested for antibacterial activity in vitro. With an inhibitory zone width of 12 mm, compound 12a had the same activity as the reference medication tobramycin against Staphylococcus aureus. Compound 12b showed 20 mg/mL as a minimum inhibitory concentration (MIC) against Bacillus subtilis. Some of the synthesized compounds were tested via molecular docking against two bacterial proteins (dihydrofolate reductase and tyrosyl-tRNA synthetase).

Yttrium Oxide nanoparticles induce cytotoxicity, genotoxicity, apoptosis, and ferroptosis in the human triple-negative breast cancer MDA-MB-231 cells.

BACKGROUND: Triple-negative breast cancer (TNBC) is a lethal mammary carcinoma subtype that affects females and is associated with a worse prognosis. Chemotherapy is the only conventional therapy available for patients with TNBC due to the lack of therapeutic targets. Yttrium oxide (Y2O3) is a rare earth metal oxide, whose nanoparticle (NPs) formulations are used in various applications, including biological imaging, the material sciences, and the chemical synthesis of inorganic chemicals. However, the biological activity of Y2O3-NPs against TNBC cells has not been fully explored. The current study was conducted to assess Y2O3-NPs' anticancer activity against the human TNBC MDA-MB-231 cell line. METHODS: Transmission electron microscopy (TEM), X-ray diffraction, Zeta potential, and dynamic light scattering (DLS) were used to characterize the Y2O3-NPs. SRB cell viability, reactive oxygen species (ROS) measurement, single-cell gel electrophoresis (comet assay), qPCR, flow cytometry, and Western blot were employed to assess the anticancer activity of the Y2O3-NPs. RESULTS: Our results indicate favorable physiochemical properties of Y2O3-NPs (with approximately average size 14 nm, Zeta Potential about - 53.2 mV, and polydispersity index = 0.630). Y2O3-NPs showed a potent cytotoxic effect against MDA-MB-231 cells, with IC50 values of 74.4 µg/mL, without cytotoxic effect on the normal retina REP1 and human dermal fibroblast HDF cell lines. Further, treatment of MDA-MB-231 cells with IC50 Y2O3-NPs resulted in increased oxidative stress, accumulation of intracellular ROS levels, and induced DNA damage assessed by Comet assay. Upon Y2O3-NPs treatment, a significant increase in the early and late phases of apoptosis was revealed in MDA-MB-231 cells. qPCR results showed that Y2O3-NPs significantly upregulated the pro-apoptotic genes CASP3 and CASP8 as well as ferroptosis-related gene heme oxygenase-1 (HO-1), whereas the anti-apoptotic gene BCL2 was significantly downregulated. CONCLUSION: This study suggests that Y2O3-NPs are safe on normal REP1 and HDF cells and exhibited a potent selective cytotoxic effect against the TNBC MDA-MB-231 cells through increasing levels of ROS generation with subsequent DNA damage, and induction of apoptosis and ferroptosis.

Novel Tetrahydro-[1,2,4]triazolo[3,4-a]isoquinoline Chalcones Suppress Breast Carcinoma through Cell Cycle Arrests and Apoptosis.

Chalcones are interesting anticancer drug candidates which have attracted much interest due to their unique structure and their extensive biological activity. Various functional modifications in chalcones have been reported, along with their pharmacological properties. In the current study, novel chalcone derivatives with the chemical base of tetrahydro-[1,2,4]triazolo[3,4-a]isoquinolin-3-yl)-3-arylprop-2-en-1-one were synthesized, and the structure of their molecules was confirmed through NMR spectroscopy. The antitumor activity of these newly synthesized chalcone derivatives was tested on mouse (Luc-4T1) and human (MDA-MB-231) breast cancer cell lines. The antiproliferative effect was evaluated through SRB screening and the MTT assay after 48 h of treatment at different concentrations. Interestingly, among the tested chalcone derivatives, chalcone analogues with a methoxy group were found to have significant anticancer activity and displayed gradient-dependent inhibition against breast cancer cell proliferation. The anticancer properties of these unique analogues were examined further by cytometric analysis of the cell cycle, quantitative PCR, and the caspases-Glo 3/7 assay. Chalcone methoxy derivatives showed the capability of cell cycle arrest and increased Bax/Bcl2 mRNA ratios as well as caspases 3/7 activity. The molecular docking analysis suggests that these chalcone methoxy derivatives may inhibit anti-apoptotic proteins, particularly cIAP1, BCL2, and EGFRK proteins. In conclusion, our findings confirm that chalcone methoxy derivatives could be considered to be potent drug candidates against breast cancer.

New Azacycles by One-Pot Three-Component Hantzsch-Like Synthesis of Tetra(hexa)azacyclopenta[a]anthracenes, Tetraazaindeno[5,4-b]fluorenes, and Oxatetraazacyclopenta[m]tetraphenes.

New Azacycles by One-Pot Three-Component Hantzsch-Like Synthesis of Tetra(hexa)azacyclopenta[a]anthracenes, Tetraazaindeno[5,4-b]fluorenes, and Oxatetraazacyclopenta[m]tetraphenes (H. Butenschön, I. A. Abdelhamid et al.) #OpenAccess Multicomponent reactions (MCRs) are envisaged as an entry point for the synthesis of heterocyclic compounds with interesting biological activities. An efficient approach to annelated tetra(hexa)azacyclopenta[a]anthracenes, tetraazaindeno[5,4-b]fluorenes, and oxatetraazacyclopenta[m]tetraphene was accomplished using a three-component reaction involving 7-amino-2-methyl-3-phenylpyrazolo[1,5-a]pyrimidin-5-one with aromatic aldehydes and the corresponding active 1,3-dicarbonyl compounds (namely, dimedone, 1,3-dimethylbarbituric acid, 1,3-indanedione, and 4-hydroxycoumarine). The reactions were conducted in glacial acetic acid at reflux for 5 h to give the desired products in good yields (62-83 %). The chemical constitutions of all new products were confirmed spectroscopically.

Novel eco-friendly [1,2,4]triazolo[3,4-a]isoquinoline chalcone derivatives efficiency against fungal deterioration of ancient Egyptian mummy cartonnage, Egypt.

Fungal deterioration is one of the major factors that significantly contribute to mummy cartonnage damage. Isolation and molecular identification of thirteen fungal species contributing to the deterioration of ancient Egyptian mummy cartonnage located in El-Lahun regions, Fayoum government, Egypt was performed. The most dominant deteriorated fungal species are Aspergillus flavus (25.70%), Aspergillus terreus (16.76%), followed by A. niger (13.97%). A newly synthesized series of tetrahydro-[1,2,4]triazolo[3,4-a]isoquinoline chalcone derivatives were synthesized and evaluated for their antifungal activities in vitro against the isolated deteriorated fungal species (Aspergillus flavus, A. niger, A. terreus, Athelia bombacina, Aureobasidium iranianum, Byssochlamys spectabilis, Cladosporium cladosporioides, C. ramotenellum, Penicillium crustosum, P. polonicum, Talaromyces atroroseus, T. minioluteus and T. purpureogenus). The most efficient chalcone derivatives are new chalcone derivative numbers 9 with minimum inhibitory concentration (MIC) ranging from 1 to 3 mg/mL followed by chalcone derivatives number 5 with MIC ranging from 1 to 4 mg/mL.

Theoretical and molecular mechanistic investigations of novel (3-(furan-2-yl)pyrazol-4-yl) chalcones against lung carcinoma cell line (A549).

A new chalcone series has been developed that may be useful in the treatment of lung cancer. The new series was confirmed by the different spectral tools. MTT assay was used to detect the cytotoxic effect of the novel chalcones against lung cancer cell line (A549). Molecular docking studies were performed on the most two effective chalcones 7b and 7c. Different molecular techniques were utilized to study the activity and the effect of two chalcones 7b and 7c on apoptosis of A549 cell line.

Chalcones: Promising therapeutic agents targeting key players and signaling pathways regulating the hallmarks of cancer.

The need for innovative anticancer treatments with high effectiveness and low toxicity is urgent due to the development of malignancies that are resistant to chemotherapeutic agents and the poor specificity of existing anticancer treatments. Chalcones are 1,3-diaryl-2-propen-1-ones, which are the precursors for flavonoids and isoflavonoids. Chalcones are readily available from a wide range of natural resources and consist of very basic chemical scaffolds. Because the ease with which the synthesis it allows for the production of several chalcone derivatives. Various in-vitro and in-vivo studies indicate that naturally occurring and synthetic chalcone derivatives exhibit promising biological activities against cancer hallmarks such as proliferation, angiogenesis, invasion, metastasis, inflammation, stemness, and regulation of cancer epigenetics. According to their structure and functional groups, chalcones derivatives and their hybrid compounds exert a broad range of biological activities through targeting key elements and signaling molecules relevant to cancer progression. This review will provide valuable insights into the latest updates of chalcone groups as anticancer agents and extensively discuss their underlying molecular mechanisms of action.

An effective uranium removal using diversified synthesized cross-linked chitosan bis-aldehyde Schiff base derivatives from aqueous solutions.

Three new cross-linked chitosan derivatives were yielded through intensification of chitosan with diverse types of bis-aldehydes. The prepared cross-linked chitosan was characterized by FTIR, 1H NMR, XRD, and TGA techniques. TGA indicated an improvement in thermal stability of the cross-linked chitosan compared with pure chitosan. Batch adsorption experiments showed that the three novel cross-linked chitosan bis-aldehyde derivatives possessed good adsorption capacity against U(VI) in the order of BFPA > BFB > BODB (adsorption capacity of the three adsorbents for U(VI) reaches 142, 124, and 114 mg/g respectively) and the adsorption isotherm and kinetic were well described by the Langmuir and the pseudo-second-order kinetic model, respectively. In addition, the prepared cross-linked chitosan bis-aldehyde derivatives were examined as U(VI) catcher from waste solutions.

Hantzsch-Like Synthesis, DNA Photocleavage, DNA/BSA Binding, and Molecular Docking Studies of Bis(sulfanediyl)bis(tetrahydro-5-deazaflavin) Analogs Linked to Naphthalene Core.

The cyclocondensation reaction of aldehydes with dimedone and bis(6-aminopyrimidin-4-one) in acetic acid led to the formation of the corresponding bis(pyrimido[4,5-b]quinoline-4,6-diones) which are known as bis(sulfanediyl)bis(tetrahydro-5-deazaflavin) analogs in a single step. Also, bis(pyrimido[4,5-b]quinoline-4,6-diones) which are linked to naphthyl core via phenoxymethyl linkage is prepared. The interactions of the synthesized compounds with DNA and bovine serum albumin (BSA) were studied. Gel electrophoresis assay was used to show the capability of the compounds to photocleave the supercoiled pBR322 plasmid DNA in UV-A (365 nm). Besides, the most photocleavable compound, bis(tetrahydropyrimido[4,5-b]quinoline-4,6-dione) linked to pyridin-3-yl at position-5 exhibits good binding affinities toward CT-DNA and BSA as supported by UV/VIS spectral studies. In addition to the experimental findings, a molecular docking simulation was performed to collect detailed binding data for this compound to both biomolecules.

[1,2,4] Triazolo [3,4-a]isoquinoline chalcone derivative exhibits anticancer activity via induction of oxidative stress, DNA damage, and apoptosis in Ehrlich solid carcinoma-bearing mice.

Despite the advances made in cancer therapeutics, their adverse effects remain a major concern, putting safer therapeutic options in high demand. Since chalcones, a group of flavonoids and isoflavonoids, act as promising anticancer agents, we aimed to evaluate the in vivo anticancer activity of a synthetic isoquinoline chalcone (CHE) in a mice model with Ehrlich solid carcinoma. Our in vivo pilot experiments revealed that the maximum tolerated body weight-adjusted CHE dose was 428 mg/kg. Female BALB/c mice were inoculated with Ehrlich ascites carcinoma cells and randomly assigned to three different CHE doses administered intraperitoneally (IP; 107, 214, and 321 mg/kg) twice a week for two consecutive weeks. A group injected with doxorubicin (DOX; 4 mg/kg IP) was used as a positive control. We found that in CHE-treated groups: (1) tumor weight was significantly decreased; (2) the total antioxidant concentration was substantially depleted in tumor tissues, resulting in elevated oxidative stress and DNA damage evidenced through DNA fragmentation and comet assays; (3) pro-apoptotic genes p53 and Bax, assessed via qPCR, were significantly upregulated. Interestingly, CHE treatment reduced immunohistochemical staining of the proliferative marker ki67, whereas BAX was increased. Notably, histopathological examination indicated that unlike DOX, CHE treatment had minimal toxicity on the liver and kidney. In conclusion, CHE exerts antitumor activity via induction of oxidative stress and DNA damage that lead to apoptosis, making CHE a promising candidate for solid tumor therapy.