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To discover new antiproliferative agents with high efficacy and selectivity, a new series of 1-aryl-3-4-[(pyridin-2-ylmethyl)thio]phenylurea derivatives (7a–7t) were designed, synthesized and evaluated for their antiproliferative activity against A549, HCT-116 and PC-3 cancer cell lines in vitro. Most of the target compounds demonstrated significant antiproliferative effects on all the selective cancer cell lines. Among them, the target compound, 1-[4-chloro-3-(trifluoromethyl)phenyl]-3-4-[3-methyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]methylthiophenylurea (7i) was identified to be the most active one against three cell lines, which was more potent than the positive control with an IC50 value of 1.53 ± 0.46, 1.11 ± 0.34 and 1.98 ± 1.27 μM, respectively. Further cellular mechanism studies confirmed that compound 7i could induce the apoptosis of A549 cells in a concentration-dependent manner and elucidated compound 7i arrests cell cycle at G1 phase by flow cytometry analysis. Herein, the studies suggested that the 1-aryl-3-4-[(pyridin-2-ylmethyl)thio]phenylurea skeleton might be regarded as new chemotypes for designing effective antiproliferative agents.

Some new Bis-pyrazoline hybrids 8-17 with dual EGFR and BRAF[sup.V600E] inhibitors have been developed. The target compounds were synthesized and tested in vitro against four cancer cell lines. Compounds 12, 15, and 17 demonstrated strong antiproliferative activity with GI[sub.50] values of 1.05 µM, 1.50 µM, and 1.20 µM, respectively. Hybrids showed dual inhibition of EGFR and BRAF[sup.V600E]. Compounds 12, 15, and 17 inhibited EGFR-like erlotinib and exhibited promising anticancer activity. Compound 12 is the most potent inhibitor of cancer cell proliferation and BRAF[sup.V600E]. Compounds 12 and 17 induced apoptosis by increasing caspase 3, 8, and Bax levels, and resulted in the downregulation of the antiapoptotic Bcl2. The molecular docking studies verified that compounds 12, 15, and 17 have the potential to be dual EGFR/BRAF[sup.V600E] inhibitors. Additionally, in silico ADMET prediction revealed that most synthesized bis-pyrazoline hybrids have low toxicity and adverse effects. DFT studies for the two most active compounds, 12 and 15, were also carried out. The values of the HOMO and LUMO energies, as well as softness and hardness, were computationally investigated using the DFT method. These findings agreed well with those of the in vitro research and molecular docking study.

BackgroundIn the recent years, the health benefits of the pigmented rice varieties have reported due to the presence of bioactive compounds. In this study, the phytochemical constituents (total phenolic, flavonoid and anthocyanin content) and individual phenolics and flavonoids of the extracts of sixteen genotypes of pigmented rice bran were evaluated using spectrophotometric and ultra-high performance liquid chromatography method. Antioxidative properties of the free and bound fractions were evaluated using nitric oxide and 1,1-diphenyl-2-picrylhydrazyl scavenging assays. Extracts were evaluated for antiproliferative activity against breast cancer cell lines (MCF-7 and MDA-MB-231) using the MTT assay.ResultsSignifficant diferences were observed in the concentrations of phytochemicals and biological activities among different pigmented rice brans. The highest phytochemical content was observed in black rice bran followed by red and brown rice bran. The concentration of free individual flavonoids and phenolic compounds were significantly higher than those of bound compounds except those of ferulic acid and p-coumaric acid. Highest antioxidant activities were observed in black rice bran, followed by red and brown rice bran extracts. Extracts of black rice bran exhibited potent antiproliferative activity, with half maximal inhibitory concentrations (IC50) of 148.6 and 119.2 mg/mL against MCF-7 and MDA-MB-231 cell lines, respectively, compared to the activity of the extracts of red rice bran (175.0 and 151.0 mg/mL, respectively) and brown rice bran (382.3 and 346.1 mg/mL, respectively).ConclusionsBlack rice bran contains high levels of phytochemicals, and thus has potent pharmaceutical activity. This highlights opportunities for researcher to breed new genotypes of rice with higher nutritional values, which the food industry can use to develop new products that will compete in expanding functional food markets.

A series of novel quinoline-based tetracyclic ring-systems were synthesized and evaluated in vitro for their antiplasmodial, antiproliferative and antimicrobial activities. The novel hydroiodide salts 10 and 21 showed the most promising antiplasmodial inhibition, with compound 10 displaying higher selectivity than the employed standards. The antiproliferative assay revealed novel pyridophenanthridine 4b to be significantly more active against human prostate cancer (IC50 = 24 nM) than Puromycin (IC50 = 270 nM) and Doxorubicin (IC50 = 830 nM), which are used for clinical treatment. Pyridocarbazoles 9 was also moderately effective against all the employed cancer cell lines and moreover showed excellent biofilm inhibition (9a: MBIC = 100 µM; 9b: MBIC = 100 µM).

Kiwifruit ( ) peel has been always considered as useless because of the harsh taste. To promote the full utilization of kiwifruit resources it is essential to explore the nutritional benefits of kiwifruit peel. Our studies explored the difference in polyphenolic composition and biological activity including antioxidant, antimicrobial, and antiproliferative activity of the flesh and peel of kiwifruit. Antioxidant activity of the extracted polyphenols of the peel and flesh of was checked by 2,2-diphenyl-1-picrylhydrazyl, 2,2'-azino-bis3-ethylbenzothiazoline-6-sulphonic acid (ABTS), hydroxyl ion reduction, and ion chelating ability. Antibacterial activity against , , and and antiproliferative activity HepG2 was tested in a dose- and time-dependent manner. Liquid chromatography/mass spectrometry (LC/MS) chromatogram of the peel and flesh further differentiated the phenolic acid profile. The pericarp of kiwifruit was found to be more abundant in polyphenols and flavonoids than the flesh, with contents of 12.8 mg/g and 2.7 mg/g, respectively. LC/MS analysis revealed that the catachin, quercetin and epigallocatechin content (the main polyphenols in kiwifruit) in the peel was significantly higher than in the flesh ( < 0.05). The antioxidant and antibacterial activity of the peel was significantly higher when compared to the flesh. Moreover, the proliferation of HepG2 cells was time- and dose-dependently inhibited by kiwifruit polyphenols, with IC values of 170 μg/mL and 291 μg/mL for peel and flesh polyphenols after 72 h of treatment time, respectively. Kiwifruit peel, with higher content of phenolics and flavonoids, exerts more potent antioxidant, antibacterial, and anticancer activity than the flesh. Our study provides scientific evidence for the development of kiwifruit, especially peel-based, novel natural products with excellent bioactivity.

The challenges of glioblastoma multiforme treatment are related to limitations in tumor removal surgery, its high heterogeneity and aggressiveness, development of resistance to standard therapy, the blood–brain barrier, and the side and toxic effects of the conventional antitumor agents used in clinical practice. Although new treatment strategies continue to emerge, progress remains slow and has not resulted in substantial improvements in patient survival. The main goal of research in recent years has been aimed at developing ways to deal with all these challenges. One of the ways to improve the control of glioblastomas is the introduction of effective new antitumor agents. Metal complexes represent a particularly promising class of compounds in this context. This is why the aim of this study was to assess the effects of six homo- and heterometallic coordination compounds bearing Schiff base ligands—[Zn2(Ampy)(µ-OH)(H2O)2](ClO4)2 (ZnAmpy), [Zn2(Dmen)(µ-OH)(H2O)2](ClO4)2 (ZnDmen), 1∞[Zn2(Ampy)(μ3-OH)2(H2O)μ-[Au(CN)2]](ClO4)3·THF·H2O (ZnAmpyAu), [Zn2(Dmen)(μ-OH)2μ-[Au(CN)2][Au(CN)2]2](ClO4)·H2O (ZnDmenAu), 1∞[Zn(Salampy)μ-Au(CN)2] (ZnSalampyAu), and 1∞[Zn(Saldmen)(μ-Au(CN)2] (ZnSaldmenAu)—on the viability and proliferation of 8MGBA and U251MG human glioblastoma multiforme cells (HDmen and HAmpy are bicompartmental Schiff base ligands resulting from the condensation of 2,6-diformyl-p-cresol with N,N-dimethylethylenediamine and 2-(aminomethyl)pyridine, respectively, while HSaldmen and HSalampy are tridentate Schiff base ligands obtained via condensation of salicylaldehyde with N,N-dimethylethylenediamine and 2-(aminomethyl)pyridine, respectively). Among these compounds, ZnSaldmenAu is a new compound and is reported here for the first time. Cytotoxicity of the compounds was evaluated through analysis of cell viability, 2D/3D growth, cytopathological alterations, and induction of cell death. The results obtained by methods with different targets in cells and the associated mechanisms of action revealed that the compounds investigated show promising cytotoxic/potential antitumor activity in treated cells.

Nowadays, one of the most important research directions that concerns the scientific world is to exploit the earth’s resources in a sustainable way. Considering the increasing interest in finding new sources of bioactive molecules and functional products, many research studies focused their interest on demonstrating the sustainability of exploiting marine macroalgal biomass as feedstock for wastewater treatment and natural fertilizer, conversion into green biofuels, active ingredients in pharmaceutical and nutraceutical products, or even for the production of functional ingredients and integration in the human food chain. The objective of the present paper was to provide an overview on the recent progress in the exploitation of different macroalgae species as a source of bioactive compounds, mainly emphasizing the latter published data regarding their potential bioactivities, health benefits, and industrial applications.

In this study, the antibacterial and antifungal properties of silver nanoparticles synthesized with the aqueous plant extract of Acer oblongifolium leaves were defined using a simplistic, environmentally friendly, reliable, and cost-effective method. The aqueous plant extract of Acer oblongifolium, which served as a capping and reducing agent, was used to biosynthesize silver nanoparticles. UV visible spectroscopy, X-ray diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR), and scanning electron microscopy were used to analyze the biosynthesized Acer oblongifolium silver nanoparticles (AgNPs). Gram-positive bacteria (Bacillus paramycoides and Bacillus cereus) and Gram-negative bacteria (E. coli) were used to test the AgNPs’ antibacterial activity. The presence of different functional groups was determined by FTIR. The AgNPs were rod-like in shape. The nanoparticles were more toxic against Escherichiacoli than both Bacillus cereus and Bacillus paramycoides. The AgNPs had IC50 values of 6.22 and 9.43 and mg/mL on HeLa and MCF-7, respectively, proving their comparatively strong potency against MCF-7. This confirmed that silver nanoparticles had strong antibacterial activity and antiproliferative ability against MCF-7 and HeLa cell lines. The mathematical modeling revealed that the pure nanoparticle had a high heat-absorbing capacity compared to the mixed nanoparticle. This research demonstrated that the biosynthesized Acer oblongifolium AgNPs could be used as an antioxidant, antibacterial, and anticancer agent in the future.

2,3,4-trisubstituted thiazoles 3a–i, having a methyl group in position four, were synthesized by the reaction of 1,4-disubstituted thiosemicarbazides with chloroacetone in ethyl acetate/Et[sub.3] N at room temperature or in ethanol under reflux. The structures of new compounds were determined using NMR spectroscopy, mass spectrometry, and elemental analyses. Moreover, the structure of compound 3a was unambiguously confirmed with X-ray analysis. The cell viability assay of 3a–i at 50 µM was greater than 87%, and none of the tested substances were cytotoxic. Compounds 3a–i demonstrated good antiproliferative activity, with GI[sub.50] values ranging from 37 to 86 nM against the four tested human cancer cell lines, compared to the reference erlotinib, which had a GI[sub.50] value of 33 nM. The most potent derivatives were found to be compounds 3a, 3c, 3d, and 3f, with GI[sub.50] values ranging from 37 nM to 54 nM. The EGFR-TK and BRAF[sup.V600E] inhibitory assays’ results matched the antiproliferative assay’s results, with the most potent derivatives, as antiproliferative agents, also being the most potent EGFR and BRAF[sup.V600E] inhibitors. The docking computations were employed to investigate the docking modes and scores of compounds 3a, 3c, 3d, and 3f toward BRAF[sup.V600E] and EGFR. Docking computations demonstrated the good affinity of compound 3f against BRAF[sup.V600E] and EGFR, with values of −8.7 and −8.5 kcal/mol, respectively.

Various organisms exist in the oceanic environment. These marine organisms provide an abundant source of potential medicines. Many marine peptides possess anticancer properties, some of which have been evaluated for treatment of human cancer in clinical trials. Marine anticancer peptides kill cancer cells through different mechanisms, such as apoptosis, disruption of the tubulin-microtubule balance, and inhibition of angiogenesis. Traditional chemotherapeutic agents have side effects and depress immune responses. Thus, the research and development of novel anticancer peptides with low toxicity to normal human cells and mechanisms of action capable of avoiding multi-drug resistance may provide a new method for anticancer treatment. This review provides useful information on the potential of marine anticancer peptides for human therapy.