Design, synthesis, and antitumor activity evaluation of BF3-o, m, p-phenylenediamine bridged with pyrimidine-indole BF3 adduction derivatives.

Fluorescent drugs and pyrimidine-indole scaffolds have been shown to have advantages in cancer treatment. Fluorescent antitumor drugs BF3-o, m, p-phenylenediamine pyrimidine-indole derivatives (PYB1, PYB2, and PYB3) were synthesized by linking pyrimidine and indole groups with aniline through a simple step and introducing BF3. The drugs exhibit promising antitumor activity and their fluorescent properties make them useful for imaging purposes. The optical properties of the three compounds have been investigated. All of them have fluorescent properties and compound PYB2 has good fluorescent properties. Additionally, the in vitro cytotoxicity of these compounds was evaluated against the human cancer cell line HeLa and the human normal cell line L02. The inhibition rates of HeLa cells treated with PYB1, PYB2, and PYB3 at a concentration of 19.2 µg/mL were 80.91%, 77.72%, and 65.94%, respectively. These results indicate a strong inhibitory effect on cancer cells. Further through the cell imaging experiment, we can see that PYB2 can enter the cell through the cell membrane through the fluorescence scattering diagram, which has good biocompatibility. In addition, the possible interactions between the compounds and Ras protein active sites were analyzed by molecular docking. The three compounds can bind well to Ras protein through hydrogen bonding. This study provides a basis for the development and modification of pyrimidine-indole fluorescent anticancer drugs. Compound PYB2 shows potential as a fluorescent anticancer drug.

A novel strategy to bind pyrimidine sulfonamide derivatives with odd even chains: exploration of their design, synthesis and biological activity evaluation.

Based on the hybridization strategy of dominant fragments, a series of pyrimidine sulfonamide (PS) derivatives were obtained by combining the pharmacophore fragments (sulfonamide group and pyrimidine group) with different biological activities, and evaluated as a new type of anticancer drug. The compounds were evaluated for in vitro cytotoxicity against four human cancer cell lines (HeLa, HCT-116, A-549 and HepG2) and the normal human cell line L02. Compared with the anti-cancer drug 5-fluorouracil (5-FU), the antiproliferative activity of compound PS14 was close to 5-FU and it has good antitumor activity. The IC50 values were 15.13 ± 2.20, 19.87 ± 2.01, 12.64 ± 3.22, 22.20 ± 1.34 and 102.46 ± 2.27 µM, respectively. The structure activity relationship was analyzed. The antitumor activity of the compound tended to increase. When the substituents of the branch chain of sulfonamides were odd. In addition, the oil-water partition coefficient was also investigated. The logP value of PS14 was between 0 and 3, indicating that PS14 was a compound with good lipophilic property, poor water solubility and easy to be absorbed and transported through cell membrane. The anti-cancer mechanism was further studied by flow cytometry. After PS14 treated HeLa, HCT-116, A-549 and HepG2, the percentage of apoptotic cells was 45.30%, 28.2%, 31.00% and 35.20%, respectively, which was higher than that of the control 5-FU. The results of cell cycle showed that PRD2 mainly blocked the cell cycle in the S phase, thereby inhibiting cell proliferation. Furthermore, molecular docking analyzed possible interactions between the compound and the PI3Kα active site, this compound has good binding with PI3Kα. Overall, this study laid the groundwork for the development and structural modification of new pyrimidine sulfonamide drugs, and PS14 could be further developed into a cancer treatment drug.

A porous form Coomassie brilliant blue G250-isorhamnetin fluorescent composite coated with acrylic resin for tumor cell imaging.

Four distinct fluorescence complexes, the fluorescent complex-1 (FC-1), fluorescent complex-2 (FC-2), fluorescent complex third (FC-3) and fluorescent complex fourth (FC-4), were created using isorhamnetin and Coomassie brilliant blue G250 as raw materials. The issue of isorhamnetin's low solubility has been resolved, and isorhamnetin-coomassie brilliant blue G250 now has better biocompatibility. Four different forms of fluorescence compounds' ultraviolet absorption spectra were identified. It was discovered that FC-2, FC-3, and FC-4, respectively, had double peaks at 483-620 nm. FC-4 had the highest ultraviolet absorption intensity, whereas FC-1 exhibited the most consistent and longest wavelength of ultraviolet absorption. Transmission electron microscopy revealed that the acrylic resin evenly disseminated the Coomassie brilliant blue G250-isorhamnetin complex in an amorphous flocculent form. Human prostate cancer cells (PC3) and human cervical cancer cells (HeLa) were investigated in the (Cell Counting Kit-8) CCK8 experiment under 10 different concentration circumstances, and the proliferation impact was 64.30% and 68.06%, respectively. Shown the complex's strong anti-tumor properties and minimal cytotoxicity. Through in vitro imaging of tumor cells, it was found that FC-1's fluorescent complex has high selectivity and can accurately infiltrate tumor cells, proving that it is biocompatible. The design not only addresses the issue of isorhamnein-Coomassie Bright Blue G250's bioavailability, but it also has an effective visual fluorescence targeting effect.

Strategy of eudragit coated curcumin nanoparticles delivery system: Release and cell imaging studies in simulated gastrointestinal microenvironments.

Curcumin has a broad-spectrum anti-tumor effect and has no toxic side effects. However, the unique diketone structure of curcumin will undergo diketo-enol tautomerism under different acid-base conditions, resulting in its instability under physiological conditions. In addition, the low biocompatibility and absorption rate of curcumin also limit the use of curcumin drugs. In this paper, curcumin was modified by substitution of acryloyl and acrylsulfonyl groups, and four kinds of nanoparticles with regular morphology were prepared using non-toxic and non-irritating acrylic resin as coating material to improve the stability and bioavailability of the compounds. Zeta potential testing shows that the composites surface carries positive charges and have good stability. In the release experiment, four complexes have the potential for slow and controlled release. Imaging of Hela cells with different channels was performed, and the imaging results showed that the complexes could enter the cells and be absorbed by them, demonstrating good imaging performance. MTT experiments have shown that the complexes have certain anti-tumor activity and low cytotoxicity. In general, the complexes synthesized in this paper have potential in the field of drug fluorescence imaging detection. At the same time, this experiment provides a new idea for the design of slow and controlled release of drugs.

Symmetry dual functional pyrimidine-BODIPY probes for imaging targeting and activity study.

Nondestructive diagnosis of tumor has always been the goal of scientists. Fluorescent dyes have become the rising star in the field of cancer diagnosis because of their excellent characteristics. Therefore, in this work, fluorescence probes d-Y-B and dO-Y-B with anti-tumor activity were constructed by introducing pyrimidine groups with high anti-tumor activity using fluorescence dye BODIPY as parent nucleus. The modified BODIPY group in the structure had the advantage of fluorescent dye, ensuring the strong fluorescence and photosensitivity of the target compound. That ethylenediamine acts as a bridge with two -NH- groups to increase molecular hydrogen bonding, and can bind firmly to multiple proteins. Co-localization of the target compounds d-Y-B and dO-Y-B with the hoechst dye for labeling living cells showed that these compounds had high biocompatibility and photostability for localization to HeLa cells. In vivo imaging in mice can realize specific localization and real-time visualization of tumor cells. The results of cytotoxicity experiments in vitro and computer software simulating molecular docking confirmed the potential of the target compounds as an anticancer agents. The bifunctional probe realized visualization of cancer cells in mice, and can kill cancer cells by anti-proliferation, which may provide a direction for future anticancer drug development.

Bioactivity and Cell Imaging of Antitumor Fluorescent Agents (Curcumin Derivatives) Coated by Two-Way Embedded Cyclodextrin Strategy.

Curcumin has a wide range of pharmacological activities, which can be used to treat tumors, inflammation and other diseases. However, curcumin's poor solubility and low bioavailability limit its application. In this article, the structure of curcumin was modified with boron trifluoride ether to change fluorescent labeling. The compounds were then embedded into the hydrophobic cavity of α-cyclodextrin and hydroxypropyl ß-cyclodextrin to form inclusion complexes. The two inclusion complexes have excellent photophysical properties, and the maximum emission wavelength is in the range of 550-565 nm. In addition, the two compounds were applied to the fluorescence imaging of HCT-116 cells and HeLa cells, and the proliferation toxicity of the compounds was detected. Both compounds showed certain inhibitory effects on the proliferation of cancer cells. In short, the fluorescent drug molecule synthesized in this article has great reference value for the development of new dosage forms of curcumin.

Water-soluble BODIPY-nido-carborane nanoparticles applied to biocompatibility tumor cell imaging.

In this article, o-carborane has a high boron content, high hydrophobicity, and good chemical stability. It has been widely used in the fields of biology and medicine, especially in the application of boron neutron capture therapy (BNCT). However, o-carborane is a fat-soluble compound, its hydrophobicity is too strong, and its bioavailability is poor. This project aims to improve the water solubility of o-carborane drugs, so that the drugs can reach specific sites. For this reason, this article provides a one-pot reaction for the synthesis of water-soluble boron-containing drugs. 2-Chloro-1-(difluoroboranyl)-5-((4-ethyl-3,5-dimethyl-2H-pyrrol-2-ylidene)(phenyl) methyl)-1H-pyrrole and ethylenediamine are used as raw materials to synthesize fluorescent molecular probe BODIPY-NH2, and the fluorescent molecular probe is reacted with P-CBMA (poly(carboxybetaine methacrylate)) to produce a water-soluble gel polymer. Water-soluble o-carborane polymers were synthesized by hydrogen bonding of the polymers with bis(4-azaspiro[3.4]octan-4-ium)-nido-ortho-carborane and bis(5-azaspiro[4.5]decan-5-ium)-nido-ortho-caborane. The two polymers were characterized and the results showed that the maximum UV absorption wavelength of the two boron polymers in different polar solutions was 530-540 nm. In the fluorescence spectrum, the maximum emission wavelengths of the two boron polymers are concentrated between 550 and 560 nm. Through electron microscopy imaging, the fluoroboron pyrrole polymers wrap the boron clusters to form a spherical stacked. Through fluorescent cell imaging, both boron polymers can enter target cells.

High activity, high selectivity and high biocompatibility BODIPY-pyrimidine derivatives for fluorescence target recognition and evaluation of inhibitory activity.

BODIPY-Pyrimidine (BP) is a highly selective, highly active, and highly biocompatible fluorescent drug, which is characterized by its own activity combined with a fluorophore. The combination of pyrimidines with good biological activity and fluorophores to obtain new compounds with both anti-tumor activity and fluorescent targeting probe functions is the focus of this research. In terms of biological activity, in vitro cytotoxicity of the compounds on four human cancer cells (HepG2, HeLa, A-459, and HCT-116) and the human normal cell line L-02 was studied. BP-4 has good antiproliferative activity, and its IC50 values are 19.12 ± 2.29, 13.47 ± 3.80, 18.59 ± 7.42, 14.57 ± 2.44 and 92.48 ± 6.03 µM, respectively. Good biocompatibility with tumor cells can be observed in cell imaging. The anti-tumor mechanism of the compound was further studied by flow cytometry. After BP-2, BP-3 and BP-4 treated HeLa cells, the percentage of apoptotic cells was 19.07%, 22.09% and 27.3%, respectively. The cell cycle study found that, compared with the positive control 5-FU (48.05%), the compounds BP-2, BP-3 and BP-4 all increased the proportion of HeLa cells in the G1 phase, reaching 57.65%, 55.46% and 53.58%, respectively. In vivo bioimaging results show that all three compounds can be targeted and accurately expressed in tumor tissues. In addition, molecular docking analyzes the possible interaction between the compound and the active site of thymidylate synthase.

Design, synthesis and biological activity of bis-sulfonyl-BODIPY probes for tumor cell imaging.

In recent years, BODIPY derivatives have become one of the research hotspots in the field of bioprobes, but most of them have the problems of poor hydrophilicity, low biocompatibility and no targeting. In this paper, novel ethylenediamine bridging bis-sulfonyl-BODIPY fluorescent probes were successfully designed and synthesized to solve these problems; What's more, the cytotoxicity analysis, cell imaging, in vivo imaging and apoptosis experiments were carried out. Ethylenediamine bridges and oxygen-rich sulfonyl groups made such probes had certain hydrophilicity, so they could be dissolved in dimethylsulfoxide and methanol. The IC50 value of compound 9 in HCT-116 cells was 93.12 ± 6.33 µM, and in HeLa cells was 89.09 ± 11.84 µM, which indicating that the probe had certain inhibitory effect on cancer cells. The excellent biocompatibility and potential tumor targeting properties of the compound were clearly observed in cell and mice imaging. This study is of great significance for the rational design of novel targeted BODIPY probes with good hydrophilicity and biocompatibility.

A Novel BODIPY Quaternary Ammonium Salt-Based Fluorescent Probe: Synthesis, Physical Properties, and Live-Cell Imaging.

The development of biological fluorescent probes is of great significance to the field of cancer bio-imaging. However, most current probes within the bulky hydrophobic group have limited application in aqueous medium and restricted imaging under physiological conditions. Herein, we proposed two efficient molecules to study their physical properties and imaging work, and the absorption and fluorescence intensity were collected with varying ions attending in aqueous medium. We enhance the water solubility through the quaternization reaction and form a balance between hydrophilic and hydrophobicity with dipyrrome-theneboron difluoride (BODIPY) fluorophore. We introduced pyridine and dimethylaminopyridine (DMAP) by quaternization and connected the BODIPY fluorophore by ethylenediamine. The final synthesized probes have achieved ideal affinity with HeLa cells (human cervical carcinoma cell line) in live-cell imaging which could be observed by Confocal Microscope. The probes also have a good affinity with subcutaneous tumor cells in mice in in vivo imaging, which may make them candidates as oncology imaging probes.

Structural basis of quinolone derivatives, inhibition of type I and II topoisomerases and inquiry into the relevance of bioactivity in odd or even branches with molecular docking study.

The structural modification of quinolone derivatives has been a hot spot in recent years, especially the modification of the N-1 position, which is the part that this article focuses on. In this paper, series of synthesized quinoline quaternary ammonium salts with odd and even carbon number alkyl groups in N-1 position were used to explain the influence of the alkyl side chain on activity. With respect to all the recently synthesized twenty products, the biological activity results exhibited significant antitumor and antibacterial activity with obvious differences in the target alkyliodine substituted compounds and the antibacterial activities apparently had the prominent odd-carbon number predominance. Compound 8-((4-(benzyloxy)phenyl)amino)-7-(ethoxycarbonyl)-5-propyl-[1,3]dioxolo[4,5-g]quinolin-5-ium (4d) was found to be the most potent derivative with IC50 values of 4 ± 0.88, 4 ± 0.42, 14±1.96, and 32±3.66 against A-549, Hela, SGC-7901, and L-02 cells, respectively, stronger than the positive control 5-FU and MTX. Furthermore, it had the most potent bacterial inhibitory activity of MIC value against E. coli (ATCC 29213) and Staphylococcus aureus (ATCC 8739) at 3.125 nmol mL-1. With respect to molecular simulations, in order to illustrate the possible mechanism of the difference between the series of compounds in the even or odd carbon chain alkyliodine substitution, this paper simulated the conceivable mode and explained the main interactions. Finally, we could find that the position and proportion of hydrogen bonds and other interactions in each series were regarded as the main reasons for this difference in activity.

Optimization of activity localization of quinoline derivatives: Design, synthesis, and dual evaluation of biological activity for potential antitumor and antibacterial agents.

A novel of quarternary amine around a quinolinium iodide combined with even number alkyl chain were prepared in a several step in moderate yield starting from malonic ester and benzo[d][1,3]dioxol-5-amine. All of the active structure compounds were identified by nuclear magnetic resonance (NMR), such as 1H NMR, 13C NMR, infrared radiation (IR), high resolution mass spectrometry (HR-MS) and Carlo Erba Instruments CHNS-O EA1108 spectra analysis. With regard to the anticancer properties, the in vitro cytotoxicity against three human cancer cell lines (A-549, Hela and SGC-7901) were evaluated. The antibacterial properties against two human bacterial strains, Escherichia coli (ATCC 29213) and Staphylococcus aureus (ATCC 8739), along with minimum inhibitory concentration (MIC) values were evaluated. The target compounds, 5-12, exhibited significant antitumor and antibacterial activity, of which compound 12 was found to be the most potent derivative with IC50 values of 5.18 ± 0.64, 7.62 ± 1.05, 17.59 ± 0.41, and 54.45 ± 4.88 against A-549, Hela, SGC-7901, and L-02 cells, respectively, stronger than the positive control 5-FU and MTX. Furthermore, compound 12 had the most potent inhibitory activity. The MIC of this compound against Escherichia coli (ATCC 29213) and Staphylococcus aureus (ATCC 8739) was 3.125 nmol·mL-1, which was smaller than that of the reference agents, amoxicillin and ciprofloxacin.

Acetonitrilated Unsymmetric BODIPYs having glycine fluorescence responsive quenching: Design, synthesis and spectroscopic properties.

A series of novel N≡C-CH2-B-F system BODIPY were designed and synthesized by introducing aldehyde and acetonitrile units which gave positive influence to spectroscopic and chemical properties of BODIPY derivatives. The effects of glycine (Gly) on the target products were studied via ultraviolet and visible spectrophotometry (UV-Vis) and photoluminescence (PL) under different conditions of the presence and absence of cations (K+, Ca2+, Zn2+). It was showed that glycine has an intense quenching effect on the compounds in both the presence and absence of ions with a dramatic color change from notable red to light orange owing to the addition of Gly. With regard to cells imaging investigation, the products showed the prominent fluorescence in cholangiocarcinoma cells. The luminescent effect of compounds 1 and 3 entering the cells was significantly stronger than that of compound 2. In addition, pertaining to anticancer properties, two human cancer cell lines (RBE, HCCC-9810) and one normal cell line (L-02) were evaluated for in vitro cytotoxicity. The target compounds, 1-3, exhibited moderate antitumor activity, of which compound 1 was found to be the most potent derivative with IC50 values of 119.31 ± 6.25, 114.73 ± 3.25, and 106.33 ± 5.22 against RBE, HCCC-9810, and L-02 cells, respectively, slightly weaker than the positive control 5-FU.

Design, Synthesis, and Dual Evaluation of Quinoline and Quinolinium Iodide Salt Derivatives as Potential Anticancer and Antibacterial Agents.

A series of novel quinoline and quinolinium iodide derivatives were designed and synthesized to discover potential anticancer and antibacterial agents. With regard to anticancer properties, in vitro cytotoxicities against three human cancer cell lines (A-549, HeLa and SGC-7901) were evaluated. The antibacterial properties against two strains, Escherichia coli (ATCC 29213) and Staphylococcus aureus (ATCC 8739), along with minimum inhibitory concentration (MIC) values were evaluated. The target alkyliodine substituted compounds exhibited significant antitumor and antibacterial activity, of which compound 8-((4-(benzyloxy)phenyl)amino)-7-(ethoxycarbonyl)-5-propyl-[1,3]dioxolo[4,5-g]quinolin-5-ium (12) was found to be the most potent derivative with IC50 values of 4.45±0.88, 4.74±0.42, 14.54±1.96, and 32.12±3.66 against A-549, HeLa, SGC-7901, and L-02 cells, respectively, stronger than the positive controls 5-FU and MTX. Furthermore, compound 12 had the most potent bacterial inhibitory activity. The MIC of this compound against both E. coli and S. aureus was 3.125 nmol ⋅ mL-1 , which was smaller than that against the reference agents amoxicillin and ciprofloxacin.

Coherent anti-Stokes Raman scattering imaging under ambient light.

We demonstrate an ambient light coherent anti-Stokes Raman scattering microscope that allows CARS imaging to be operated under environmental light for field use. The CARS signal is modulated at megahertz frequency and detected by a photodiode equipped with a lab-built resonant amplifier, then extracted through a lock-in amplifier. The filters in both the spectral domain and the frequency domain effectively blocked the room light contamination of the CARS image. In situ hyperspectral CARS imaging of tumor tissue under ambient light is demonstrated.