C60 Derivatives Research Articles

The charge transport properties of dicyanomethylene-functionalised violanthrone derivatives.

The study of organic small molecule semiconductor materials as active components of organic electronic devices continues to attract considerable attention due to the range of advantages these molecules can offer. Here, we report the synthesis of three dicyanomethylene-functionalised violanthrone derivatives (3a, 3b and 3c) featuring different alkyl substituents. It is found that the introduction of the electron-deficient dicyanomethylene groups significantly improves the optical absorption compared to their previously reported precursors 2a-c. All compounds are p-type semiconductors with low HOMO-LUMO gaps (≈1.25 eV). The hole mobilities, measured from fabricated organic field-effect transistors, range from 3.6 × 10-6 to 1.0 × 10-2 cm2 V-1 s-1. We found that the compounds featuring linear alkyl chains (3b and 3c) displayed a higher mobility compared to the one with branched alkyl chains, 3a. This could be the result of the more highly disordered packing arrangement of this molecule in the solid state, induced by the branched side chains that hinder the formation of π-π stacking interactions. The influence of dicyanomethylene groups on the charge transport properties was most clearly observed in compound 3b which has a 60-fold improvement in mobility compared to 2b. This study demonstrates that the choice of the solubilising group has a profound effect on the hole mobility on these organic semiconductors.

Synthesis of S-alkylated oxadiazole bearing imidazo[2,1-b]thiazole derivatives targeting breast cancer: In vitro cytotoxic evaluation and in vivo radioactive tracing studies

Breast cancer is the most common invasive cancer diagnosed in women, accounting for most cancer-related fatalities globally. Numerous investigations have revealed that breast cancer is characterized by abnormal expression and maintenance of EGFR levels. In terms of structural study and optimization of several EGFR inhibitors, two series of oxadiazole bearing imidazo[2,1-b]thiazole derivatives were designed and synthesized as potential EGFR inhibitors and assessed for their antitumor activity at NCI-USA. Four derivatives 3b, 3c, 3d and 3e elicited remarkable GI% against MDA-MB-468, T-47D and MCF-7 breast cancer cell lines. Thereafter, MTT assay was performed to reveal that compounds 3b (IC50 = 2.27 µM) and 3d (IC50 = 1.46 µM) showed promising cytotoxic activity against MCF-7 and MDA-MB-468 cell lines, respectively, compared to their reference drugs. Compounds 3b, 3d and 3e revealed good selectivity toward tumor cells with reasonable safety profile when tested against the normal cell line MCF-10a. In vitro EGFR inhibitory assay demonstrated that compounds 3b (IC50 = 0.099 µM) and 3d (IC50 = 0.086 µM) exhibited comparable inhibitory activity to the standard drug erlotinib (IC50 = 0.046 µM). A flow cytometric analysis demonstrated that derivatives 3b and 3d arrested the cell cycle at the S phase in MCF-7 and MDB-MB-468, respectively. Furthermore, the most active derivative 3d was subjected to in vivo radioactive studies. In-vivo biodistribution of 99mTc-3d complex showed a notable elevated accumulation in the targeted sarcoma muscle, indicating the targeting capacity of compound 3d in the tumor of sarcoma mice model. The binding mode of compounds 3b and 3d with EGFR was studied by molecular docking and was further inspected by molecular dynamic simulations. Both compounds were shown to be stable during the course of simulation and demonstrated a plausible interaction pattern with the EGFR binding pocket.

Synthesis and Molecular Docking Study of Hydrazone Schiff Bases of α‐Naphthalene‐Containing Alkyl Phenyl Ether Fragment as Potent α‐Amylase and α‐Glucosidase Inhibitors

AbstractIn this study, new Schiff base derivatives of α‐naphthalene acetic acid containing alkyl phenyl ether fragment have been effectively synthesized through multistep reaction process, characterized by 1H‐NMR and 13C‐NMR spectroscopy. These derivatives have been tested for their in vitro α‐amylase and α‐glucosidase inhibitory activities. In the series, 8 compounds (2j, 2f, 2e, 2m, 2a, 2b, 2l, and 2c) exhibited promising α‐amylase inhibition with IC50 values from 5.38 ± 0.36 to 14.59 ± 0.64 µg/mL. Similarly, in the case of α‐glucosidase inhibitory activity, 10 derivatives (2e, 2f, 2j, 2m, 2b, 2c, 2i, 2d, 2a, and 2l) exhibited excellent activity having IC50 values from 6.96 ± 0.39 to 16.27 ± 0.31 µg/mL, wheras the remaining derivatives exhibited good‐to‐least antidiabetic potential. The ADME properties were calculated for all Schiff base derivatives using Swiss‐ADME web tool. Furthermore, the docking studies identified the binding modes of the compounds.

Synthesis of bis-Chalcones Based on Green Chemistry Strategies and Their Cytotoxicity Toward Human MeWo and A375 Melanoma Cell Lines.

Chalcone is an aromatic ketone that forms the central core of many important biological compounds. Chalcone derivatives show various biological activities, especially anti-inflammatory, antibacterial, antioxidant, and anticancer activities, and also inhibit melanoma cell growth. In this study, we synthesized chalcone compounds with bis-chalcone's chemical structure under microwave (MW) and microwave-ultrasound (MW-US) conditions and compared them to chalcones produced using the classical synthesis method. All bis-chalcones were synthesized with terephthalaldehyde and an appropriate aromatic ketone as substrates in Claisen-Schmidt condensation. All the obtained compounds were tested regarding their roles as potential anticancer agents. The cytotoxic effect of the bis-chalcones against human MeWo and A375 melanoma cell lines was investigated through colorimetric MTT and SRB assays. The data were analyzed statistically. In the case of the synthesis of bis-chalcones, it was determined that the use of green conditions supported by the MW or MW-US factors led to an increase in the yield of the final products and a reduction in the reaction time compared to the classic method. The biological results showed the high cytotoxic effect of bis-chalcones. The present results show the compounds' high antiproliferative and cytotoxic potential, especially for the two selected bis-chalcone derivatives (3b and 3c), in particular, at concentrations of 50 μM-200 μM at 24, 48 h, and 72 h of incubation. The use of MW and US for the synthesis of bis-chalcones significantly improved the process compared to the classical method. The derivatives containing two hydroxy and two methoxy groups were the most effective against the tested cancer cells.

Interaction of a pyrene derivative with cationic [60]fullerene in phospholipid membranes and its effects on photodynamic actions.

We have reported that upon visible light irradiation, ferrocene-porphyrin-[60]fullerene triad molecules yield long-lived charge-separated states, enabling the control of the plasma membrane potential (V m) in living cells. These previous studies indicated that the localization of the triad molecules in a specific intra-membrane orientation and the suppression of the photodynamic actions of the [60]fullerene (C60) moiety are likely important to achieve fast and safe control of V m, respectively. In this study, by mimicking our previous system of triad molecules and living cells, we report a simplified model system with a cationic C60 derivative (catC60) and a liposome with embedded 1-pyrenebutyric acid (PyBA) to demonstrate that the addition of PyBA was important to achieve fast and safer control of V m.

Synthesis, Antibacterial, Anti-Biofilm Properties, and Docking Study of Indeno[1,2-b]Pyridin-5-One Derivatives

In this context, we designed and synthesized a series of hydrazonal and their related indeno[1,2-b]pyridin-5-one derivatives to investigate their antibacterial and anti-biofilm properties. Several of the synthesized compounds exhibited significant efficacy against all microorganism species tested. Most of the compounds demonstrated favorable results when tested against Gram-positive bacteria. The derivatives 4a, 4f, 6c, and 6f exhibit the highest antimicrobial efficacy, as indicated by their minimum inhibitory concentration (MIC) values ranging from 4 to 512 μg/mL. We conducted additional investigations on 4a, 6c, and 6f for the purpose of examining their synergy using Checkerboard assay. Compound 6c demonstrated a synergistic impact against methicillin-sensitive Staphylococcus aureus (MSSA) and Pseudomonas aeruginosa, while exhibiting moderate synergistic activity against methicillin-resistant Staphylococcus aureus (MRSA). In addition, the simultaneous use of gentamycin with compounds 4a and 6f demonstrates a synergistic impact in fighting against methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa, respectively. Three chosen compounds were evaluated for their antibiofilm efficacy. Application of 4a, 6c, and 6f effectively reduced the production of biofilms in MRSA, MSSA, and Pseudomonas aeruginosa, resulting in a significant decrease compared to the untreated samples. In addition, ADME and pharmacokinetic analyses were conducted for the three most potent derivatives, namely 4a, 6c, and 6f. Compounds 4a and 6c were subjected to docking in the LasR Quorum-Sensing Receptor, whereas compounds 6c and 6f were docked in the sortase enzyme.

New S-substituted-3-phenyltetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4(3H)-one scaffold with promising anticancer activity profile through the regulation and inhibition of mutated B-RAF signaling pathway.

Novel 3-phenyltetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine derivatives were synthesized and screened for their antiproliferative activity against a panel of 60 cancer cell lines. Derivatives 5b, 5f, and 9c showed significant antitumor activity at a single dose with mean growth inhibition of 55.62%, 55.79%, and 71.40%, respectively. These compounds were further investigated against HCT-116, colon cancer cell line, and FHC, normal colon cell line. Compound 9c showed the highest activity with IC50 = 0.904 ± 0.03 µM and SI = 20.42 excelling doxorubicin which scored IC50 = 2.556 ± 0.09 µM and SI = 6.19. Compound 9c was also the most potent against B-RAFWT and mutated B-RAFV600E with IC50 = 0.145 ± 0.005 and 0.042 ± 0.002 µM, respectively in comparison with vemurafenib with IC50 = 0.229 ± 0.008 and 0.038 ± 0.001 µM, respectively. The cell cycle analysis showed that 9c increased the cell population and induced an arrest in the cell cycle of HCT-116 cancer cells at the G0-G1 stage with 1.23-fold. Apoptosis evaluation showed that compound 9c displayed an 18.18-fold elevation in total apoptosis of HCT-116 cancer cells in comparison to the control. Compound 9c increased the content of caspase-3 by 3.52-fold versus the control. A molecular modeling study determined the binding profile and interaction of 9c with the B-RAF active site.

Exploring the 3,5-Dibromo-4,6-dimethoxychalcones and Their Flavone Derivatives as Dual α-Glucosidase and α-Amylase Inhibitors with Antioxidant and Anticancer Potential.

The rising levels of type 2 diabetes mellitus (T2DM) and the poor medical effects of the commercially available antidiabetic drugs necessitate the development of potent analogs to treat this multifactorial metabolic disorder. It has been demonstrated that targeting two or more biochemical targets associated with the onset and progression of diabetes along with oxidative stress and/or cancer could be a significant strategy for treating complications related to this metabolic disorder. The 3,5-dibromo-4,6-dimethoxychalcones (2a-f) and the corresponding flavone derivatives (3a-f) were synthesized and characterized using spectroscopic (NMR, HR-MS and FT-IR) techniques. The inhibitory effect of both series of compounds against α-glucosidase and α-amylase was evaluated in vitro through enzymatic assays. Selected compounds were also evaluated for potential to activate or inhibit superoxide dismutase. Compound 3c was selected as a representative model for the flavone series and evaluated spectrophotometrically for potential to coordinate Cu(II) and/or Zn(II) ions implicated in the metal-catalyzed free radical generation. A plausible mechanism for metal-chelation of the test compounds is presented. Furthermore, the most active compounds from each series against the test carbohydrate-hydrolyzing enzymes were selected and evaluated for their antigrowth effect on the human breast (MCF-7) and lung (A549) cancer cell lines and for cytotoxicity against the African Green Monkey kidney (Vero) cell line. The parent chalcone 2a and flavone derivatives 3a, 3c and 3e exhibited relatively high inhibitory activity against the MCF-7 cells with IC50 values of 4.12 ± 0.55, 8.50 ± 0.82, 5.10 ± 0.61 and 6.96 ± 0.66 μM, respectively. The chalcones 2a and 2c exhibited significant cytotoxicity against the A549 cells with IC50 values of 7.40 ± 0.67 and 9.68 ± 0.80 μM, respectively. Only flavone 3c exhibited relatively strong and comparable cytotoxicity against the MCF-7 and A549 cell lines with IC50 values of 6.96 ± 0.66 and 6.42 ± 0.79 μM, respectively. Both series of compounds exhibited strong activity against the MCF-7 and A549 cell lines compared to the analogous quercetin (IC50 = 35.40 ± 1.78 and 35.38 ± 1.78 μM, respectively) though moderate compared to nintedanib (IC50 = 0.53 ± 0.11 and 0.74 ± 0.15 μM, respectively). The test compounds generally exhibited reduced cytotoxicity against the Vero cells compared to this anticancer drug. Molecular docking revealed strong alignment of the test compounds with the enzyme backbone to engage in hydrogen bonding interaction/s and hydrophobic contacts with the residues in the active sites of α-glucosidase and α-amylase. The test compounds possess favorable drug-likeness properties, supporting their potential as therapeutic candidates against T2DM.

Dose-Response Effect of Various Concentrations of Cl-Containing Water-Soluble Derivatives of C60 Fullerenes on a Selective Regulation of Gene Expression in Human Embryonic Lung Fibroblasts (HELF).

The new synthesized water-soluble derivatives of C60 fullerenes are of a great interest to researchers since they can potentially be promising materials for drug delivery, bioimaging, biosonding, and tissue engineering. Surface functionalization of fullerene derivatives changes their chemical and physical characteristics, increasing their solubility and suitability for different biological systems applications, however, any changes in functionalized fullerenes can modulate their cytotoxicity and antioxidant properties. The toxic or protective effect of fullerene derivatives on cells is realized through the activation or inhibition of genes and proteins of key signaling pathways in cells responsible for regulation of cellular reactive oxygen species (ROS) level, proliferation, and apoptosis. The 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay was used to assess cells viability. Flow cytometry analyses was applied to measure proteins levels in human embryonic lung fibroblasts (HELF) cells. HELF is a standard, stable and well described human cell line that can be passaged many times. Quantitation of ROS was assessed using H2DCFH-DA. Fluorescence images were obtained using microscopy. Expression of BCL2, CCND1, CDKN2A, BRCA1, BAX, NFKB1, NOX4, NRF2, TBP (reference gene) was analyzed using real-time Polymerase chain reaction (PCR). We found that high and low concentrations of fullerene C60 derivatives with the five residues of potassium salt of 6-(3-phenylpropanamido)hexanoic (F1) or 6-(2-(thiophen-2-yl)acetamido)hexanoic (F2) acid and a chlorine atom attached directly to the cage cause diametrically opposite activation of genes and proteins of key signaling pathways regulating the level of oxidative stress and apoptosis in HELF. High concentrations of F1 and F2 have a genotoxic effect, causing NADPH oxidase 4 (NOX4) expression activation in 24-72 hours (2-4 fold increase), ROS synthesis induction (increase by 30-40%), DNA damage and breaks (2-2.5 fold 8-oxodG level increases), and activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) (by 40-80%) against the background of reduced NF-E2-related factor 2 (NRF2) expression (by 20-45%). Low concentrations of F1 and F2 produced a cytoprotective effect: in 24-72 hours they reduce the oxidative DNA damage (by 20-40%), decrease the number of double-strand DNA breaks (by 20-30%), increase the level of anti-apoptotic proteins and enhance the antioxidant response activating the NRF2 expression (NRF2 gene expression increases 1.5-2.3 fold, phosphorylated form of the NRF2 protein increases 2-3 fold). Obtained results show that in low doses studied fullrens may serve as perspective DNA protectors against the damaging genotoxic factors.

Development of potential cathepsin B inhibitors: Synthesis of new bithiazole derivatives, in vitro studies supported with theoretical docking studies

Cysteine cathepsins play a crucial role in cancer, inflammation, and the regulation of degenerative processes such as apoptosis, making them significant targets in drug development. In this study, we designed, synthesized, and characterized sixteen novel bi-thiazole derivatives, confirmed by 1H NMR, 13C NMR, HRMS, and X-ray analysis, which demonstrated significant therapeutic potential as inhibitors of cathepsin B. The synthesized thiazoles showed % inhibition in the range of 59.11–77.32, out of which bis-methoxyphenyl derivative 8k showed the highest inhibition of 77.32 % with IC50 and ki values of 1.04 nM and 0.52 nM, respectively. Methoxy-containing derivatives 8c, 8g, 8i, 8j, 8l, and 8o showed improved inhibition over methyl and chloro. In silico studies of the new bis-thiazole compounds at cathepsin B active sites supported the in vitro findings, indicating that the synthesized bis-thiazole esters are promising therapeutic candidates for conditions involving elevated cathepsin B levels.

Hydrogen‐Bonded Cyclic Tetramer Formation of a Pyridylethynylimidazole‐Based Fluorophore

AbstractSupramolecular have promising application prospects owing to their catalytic, self‐healing, and stimulus‐responsive functions. Pyridylethynylimidazole‐based supramolecular synthons with fluorescent properties have been developed. 4‐(2‐Pyridylethynyl)‐5‐arylethynyl‐1H‐imidazole derivatives 1 with different substituents at the 4‐ and 5‐positions of the imidazole skeleton were prepared using a step‐by‐step Sonogashira coupling reaction. The fluorescence maxima of phenyl‐ and methoxyphenyl‐substituted derivatives 1a and 1c were independent of solvent polarity. On the other hand, ester‐ and cyano‐substituted 1b and 1d showed bathochromically shifted fluorescence maxima in highly polar solvents. In crystals, the 4‐(2‐pyridylethynyl)‐5‐arylethynyl‐1H‐imidazole derivatives formed a supramolecular cyclic tetramer structure via two hydrogen bonds: one was between N─H in imidazole and N in pyridine, and the other was between C─H in imidazole and N in imidazole. Introducing the pyridine ring as a hydrogen bond acceptor, in addition to the imidazole ring, promoted the unique cyclic tetramer structure formation.

Anti-Diabetic Activities and Molecular Docking Studies of Aryl-Substituted Pyrazolo[3,4-b]pyridine Derivatives Synthesized via Suzuki Cross-Coupling Reaction.

Pyrazolo[3,4-b]pyridine scaffolds have been heavily exploited in the development of nitrogen-containing heterocycles with numerous therapeutic applications in the field of medicinal and pharmaceutical chemistry. The present work describes the synthesis of eighteen biaryl pyrazolo[3,4-b]pyridine ester (6a-i) and hydrazide (7a-i) derivatives via the Suzuki cross-coupling reaction. These derivatives were subsequently screened for their therapeutic potential to inhibit the diabetic α-amylase enzyme, which is a key facet of the development of anti-diabetic agents. Initially, the ethyl 4-(4-bromophenyl)-3-methyl-1-phenyl-1H-pyrazolo[3,4-b]pyridine-6-carboxylate 4 was synthesized through a modified Doebner method under solvent-free conditions, providing an intermediate for further derivatization with a 60% yield. This intermediate 4 was subjected to Suzuki cross-coupling, reacting with electronically diverse aryl boronic acids to obtain the corresponding pyrazolo[3,4-b]pyridine ester derivatives (6a-i). Following this, the biaryl ester derivatives (6a-i) were converted into hydrazide derivatives (7a-i) through a straightforward reaction with hydrazine monohydrate and were characterized using 1H-NMR, 13C-NMR, and LC-MS spectroscopic techniques. These derivatives were screened for their α-amylase inhibitory chemotherapeutic efficacy, and most of the biaryl ester and hydrazide derivatives demonstrated promising amylase inhibition. In the (6a-i) series, the compounds 6b, 6c, 6h, and 6g exhibited excellent inhibition, with almost similar IC50 values of 5.14, 5.15, 5.56, and 5.20 μM, respectively. Similarly, in the series (7a-i), the derivatives 7a, 7b, 7c, 7d, 7f, 7g, and 7h displayed excellent anti-diabetic activities of 5.21, 5.18, 5.17, 5.12, 5.10, 5.16, and 5.19 μM, respectively. These in vitro results were compared with the reference drug acarbose (IC50 = 200.1 ± 0.15 μM), demonstrating better anti-diabetic inhibitory activity in comparison to the reference drug. The in silico molecular docking study results were consistent with the experimental biological findings, thereby supporting the in vitro pharmaceutical efficacy of the synthesized derivatives.

Phytotoxic and Cytogenetic Assessment of Glycerol Triazole Derivatives in Model Plants and Weeds.

Weed invasion represents a challenge for farmers, who typically manage it with herbicides. However, this approach raises concerns about environmental and human health, as well as increasing resistance in these plants with continued use. Therefore, exploring alternative methods, such as heterocyclic compounds, triazoles, is essential due to their biological and environmental relevance. This study aimed to evaluate the effects of twelve 1,2,3-triazoles on the germination and early development of Lactuca sativa, Bidens pilosa, and Lolium multiflorum, as well as their impact on cell division in the cells of L. sativa. Triazole derivatives 4a, 4b, 4c, 4g, 4h, 4i, 4k, and 4l exhibited phytotoxicity, showing varying levels of inhibition in germination, germination speed index, and root growth. Chlorinated compounds were the most detrimental to lettuce development. B. pilosa was notably affected by compounds 4h, 4i, 4k, and 4l, while L. multiflorum responded most to triazoles 4c and 4l, with effectiveness comparable to that of the herbicide glyphosate. All derivatives, except 4l, exhibited aneugenic mechanisms of action, and 4a, 4b, 4c, 4e, 4f, and 4g showed clastogenic effects. This study demonstrated the potential of triazoles as effective agents against weed growth, with mechanisms that warrant further investigation for agricultural applications.

A Quantum Mechanical MP2 Study of the Electronic Effect of Nonplanarity on the Carbon Pyramidalization of Fullerene C60.

Among C60's diverse functionalities, its potential application in CO2 sequestration has gained increasing interest. However, the processes involved are sensitive to the molecule's electronic structure, aspects of which remain debated and require greater precision. To address this, we performed structural optimization of fullerene C60 using the QM MP2/6-31G* method. The nonplanarity of the optimized icosahedron is characterized by two types of dihedral angles: 138° and 143°. The 120 dihedrals of 138° occur between two hexagons intersecting at C-C bonds of 1.42 Å, while the 60 dihedrals of 143° are observed between hexagons and pentagons at C-C bonds of 1.47 Å. NBO analysis reveals less pyramidal sp1.78 hybridization for carbons at the 1.42 Å bonds and more pyramidal sp2.13 hybridization for the 1.47 Å bonds. Electrostatic potential charges range from -0.04 a.u. to 0.04 a.u. on the carbon atoms. Second-order perturbation analysis indicates that delocalization interactions in the C-C bonds of 1.42 Å (143.70 kcal/mol) and 1.47 Å (34.98 kcal/mol) are 22% and 38% higher, respectively, than those in benzene. MP2/Def2SVP calculations yield a correlation energy of 13.49 kcal/mol per electron for C60, slightly higher than the 11.68 kcal/mol for benzene. However, the results from HOMO-LUMO calculations should be interpreted with caution. This study may assist in the rational design of fullerene C60 derivatives for CO2 reduction systems.

Synthesis, anticancer activity, molecular docking, ADMET analysis and dynamic simulations of a novel series of thiazole derivatives based on furan-2-carbaldehyde thiosemicarbazone

The study presents construct of newly thiazole derivatives analogues over a multicomponent reaction connecting Furan-2-carbaldehyde thiosemicarbazone. The synthesized compounds were described by spectroscopic studies (FT-IR, ESI-MS and NMR). All new compounds were estimated for their cytotoxicity inverse breast cancer cell line (MDA-MB231). The new pyrazole derivatives 16c, 8a, and 9c compounds most effective to (MDA-MB231) cells. Compound 16c is predicted to have promising oral absorption, good drug-likeness and low toxicity risks. Also, MD simulations revealed stable complexes of 16c with EGFR, Estrogen Receptor, and HER2 with RMSD (0.20–0.35, 0.30–0.45, and 0.30–0.40 nm), RMSF (0.10–0.40, 0.10–0.40, and 0.10–0.45 nm), SASA (140–150, 120–130, and 140–150nm2) and Rg (1.95–2.00, 1.80–1.90, and 2.00–2.10 nm). These findings provide further support for the potential of these compounds in ongoing drug development endeavors.

An environment-friendly phosphotungstic acid catalyzed cross-dehydrogenative coupling reaction to synthesize 9-substituted-9H-xanthenes with photoelectrochemical performance

An environment-friendly phosphotungstic acid catalyzed cross-dehydrogenative coupling reaction for the synthesis of 9-substituted-9H-xanthenes under oxygen and solvent-free conditions have been developed. The economic and practical reaction exhibited good substrate applicability tolerance, various 9-substituted-9H-xanthenes were synthesized in moderate to excellent yields by tuning the ratio of xanthenes and ketones (22 examples, up to 99% yield). By testing the photoelectrochemical performance, some of the xanthene derivatives (10c, 12c, 13c and 2d) showed stable photocurrent value, especially 2d had better cathode photocurrent value and application potential.

Synthesis and Antimicrobial Activity of (E)-1-Aryl-2-(1H-tetrazol-5-yl)acrylonitrile Derivatives via [3+2] Cycloaddition Reaction Using Reusable Heterogeneous Nanocatalyst under Microwave Irradiation.

The magnetically recoverable heterogeneous Fe2O3@cellulose@Mn nanocomposite was synthesized by a stepwise fabrication of Mn nanoparticles on cellulose-modified magnetic Fe2O3 nanocomposites, and the morphology of the nanocomposite was characterized through advanced spectroscopic techniques. This nanocomposite was investigated as a heterogeneous catalyst for the synthesis of medicinally important tetrazole derivatives through Knoevenagel condensation between aromatic/heteroaromatic aldehyde and malononitrile followed by [3+2] cycloaddition reaction with sodium azide. Thirteen potent (E)-1-aryl-2-(1H-tetrazol-5-yl)acrylonitrile derivatives are reported in this paper with very high yields (up to 98%) and with excellent purity (as crystals) in a very short period (3 min @ 120 W) using microwave irradiation. The present procedure offers several advantages over recent protocols, including minimal catalyst loading, quick reaction time, and the utilization of an eco-friendly solvent. Furthermore, the synthesized (E)-1-aryl-2-(1H-tetrazol-5-yl)acrylonitrile derivatives (4b, 4c, and 4m) are shown to have excellent resistance against various fungal strains over bacterial strains as compared to the standard drugs Cefixime (4 μg/mL) and Fluconazole (2 μg/mL).

6-Substituted benzo[d]thiazole linked 2-(2-(bis (1H-benzo[d]imidazol-2-yl) methylene) hydrazineyl compounds: Synthesis, computational studies, and in-vitro anticancer assessment

In this study, four novel 6-substituted benzothiazole-linked bis-benzimidazoles (3a–d) were synthesized and characterized using 1H NMR, 13C NMR, FTIR, and HRMS techniques. The physicochemical properties of these compounds were examined, and experimental data validated the computed values. The absorption and emission properties were also investigated using carbonate, acetate, and phosphate buffers at various pH levels.In-silico studies revealed that methoxy derivative (3c) possesses the highest docking affinity for tyrosine kinase. Pharmacokinetic studies showed that, like the marketed drug erlotinib, none of the compounds act as substrates for p-glycoprotein, and all except compound 3d do not inhibit CYP-2C9. The gastrointestinal absorption profiles, including blood-brain barrier permeability, were also studied. Drug-likeness assessments based on Lipinski's rule of five and Ghose criteria suggested favourable properties, though some compounds showed deviations in molecular weight and logP values. In-vitro anticancer study via MTT assay includes its potency against MCF-7 and MDA-MB-231 breast cancer cell lines, including 3c as the most potent against MCF-7 cells, which coincides with the In-silico study.

Synthesis and Preliminary Anticancer Evaluation of 4-C Derivatives of Diphyllin.

The natural lignan diphyllin has shown promising antitumor activity, although its clinical advancement has been impeded by challenges such as low solubility, poor metabolic stability, and limited potency. In response, we developed and synthesized two sets of diphyllin 4-C derivatives, comprising six ester derivatives and eight 1, 2, 3-triazole derivatives. Notably, among these derivatives, 1, 2, 3-triazole derivatives 7c and 7e demonstrated the most potent cytotoxic effects, with IC50 values ranging from 0.003 to 0.01 μM. Treatment with 0.2 μM of 7c and 7e resulted in a reduction of V-ATPase activity in HGC-27 cells to 23% and 29%, respectively.

The Cytoprotective Effect of C60 Derivatives in the Self-Microemulsifying Drug Delivery System against Triptolide-Induced Cytotoxicity In Vitro.

The aim of this study was to optimize the formulation of a C60-modified self-microemulsifying drug delivery system loaded with triptolide (C60-SMEDDS/TP) and evaluate the cytoprotective effect of the C60-SMEDDS/TP on normal human cells. The C60-SMEDDS/TP exhibited rapid emulsification, an optimal particle size distribution of 50 ± 0.19 nm (PDI 0.211 ± 0.049), and a near-neutral zeta potential of -1.60 mV. The release kinetics of TP from the C60-SMEDDS/TP exhibited a sustained release profile and followed pseudo-first-order release kinetics. Cellular proliferation and apoptosis analysis indicated that the C60-SMEDDS/TP (with a mass ratio of TP: DSPE-PEG-C60 = 1:10) exhibited lower toxicity towards L02 and GES-1 cells. This was demonstrated by a higher IC50 (40.88 nM on L02 cells and 17.22 nM on GES-1 cells) compared to free TP (21.3 nM and 11.1 nM), and a lower apoptosis rate (20.8% on L02 cells and 26.3% on GES-1 cells, respectively) compared to free TP (50.5% and 47.0%) at a concentration of 50 nM. In comparison to the free TP group, L02 cells and GES-1 cells exposed to the C60-SMEDDS/TP exhibited a significant decrease in intracellular ROS and an increase in mitochondrial membrane potential (ΔψM). On the other hand, the C60-SMEDDS/TP demonstrated a similar inhibitory effect on BEL-7402 cells (IC50 = 28.9 nM) and HepG2 cells (IC50 = 107.6 nM), comparable to that of the free TP (27.2 nM and 90.4 nM). The C60-SMEDDS/TP group also exhibited a similar intracellular level of ROS and mitochondrial membrane potential compared to the SMEDDS/TP and free TP groups. Fullerenol-Grafted Distearoyl Phosphatidylethanolamine-Polyethylene Glycol (DSPE-PEG-C60) was synthesized and applied in the self-microemulsifying drug delivery system. The C60-SMEDDS/TP was formulated using Cremophor EL, medium-chain triglycerides (MCT), PEG-400, and DSPE-PEG-C60, and loaded with triptolide (TP). The toxicity and bioactivity of the C60-SMEDDS/TP were assessed using normal human liver cell lines (L02 cells), normal human gastric mucosal epithelial cell lines (GES-1 cells), and liver cancer cell lines (BEL-7402 cells and HepG2 cells). The production of reactive oxygen species (ROS) after the C60-SMEDDS/TP treatment was assessed using 2',7'-dichlorofluorescein diacetate (DCFDA) staining. The alterations in mitochondrial membrane potential (ΔψM) were assessed by measuring JC-1 fluorescence. The cytoprotection provided by the C60-SMEDDS/TP favored normal cells (L02 and GES-1) over tumor cells (BEL-7402 and HepG2 cells) in vitro. This suggests a promising approach for the safe and effective treatment of TP.