Green synthesis and characterization of hexagonal shaped MgO nanoparticles using insulin plant (Costus pictus D. Don) leave extract and its antimicrobial as well as anticancer activity

Green synthesis is an ecofriendly novel technology and attractive research area for the production of metal oxide nanoparticles in bio-medical and chemical applications. The green perspective includes solvents, reductants or stabilizing agents obtained from a natural resource as they are non-toxic and ecofriendly. In this study, a sustainable green synthetic strategy to synthesize magnesium oxide nanoparticles by employing Costus pictus D. Don plant leaf extract as a reducing agent. The successful formation of magnesium oxide nanoparticles was confirmed by comprehensive characterization techniques. The presence of biomolecules and metal oxides were confirmed by Fourier transform Infrared (FT-IR) spectral data analysis. The X-ray diffraction (XRD) revealed the formation of pure cubic MgO crystalline nanoparticles. The surface morphology of MgO particles observed by Scanning electron microscope (SEM) showed the hexagonal-shaped MgO crystallites. The average size of biosynthesized MgO nanoparticles was measured to be around 50?nm by Transmission Electron Microscopy (TEM). The mechanism for the formation of MgO nanoparticles was suggested in this study. The biosynthesized magnesium oxide particles showed good antimicrobial and exhibited maximum inhibition rate for MgO nanoparticles at 200?µg showing efficient anticancer activity.     

Anticancer Agents Derived from Cyclic Thiosulfonates: Structure-Reactivity and Structure-Activity Relationships

Reported are structure-property-function relationships associated with a class of cyclic thiosulfonate molecules—disulfide-bond disrupting agents (DDAs)—with the ability to downregulate the Epidermal Growth Factor Receptor (HER) family in parallel and selectively induce apoptosis of EGFR+ or HER2+ breast cancer cells. Recent findings have revealed that the DDA mechanism of action involves covalent binding to the thiol(ate) from the active site cysteine residue of members of the protein disulfide isomerase (PDI) family. Reported is how structural modifications to the pharmacophore can alter the anticancer activity of cyclic thiosulfonates by tuning the dynamics of thiol-thiosulfonate exchange reactions, and the studies reveal a correlation between the biological potency and thiol-reactivity. Specificity of the cyclic thiosulfonate ring-opening reaction by a nucleophilic attack can be modulated by substituent addition to a parent scaffold. Lead compound optimization efforts are also reported, and have resulted in a considerable decrease of the IC₅₀/IC₉₀ values toward HER-family overexpressing breast cancer cells.     

抗癌药物卡铂薄层色谱分析方法研究

研究抗癌药卡铂薄层色谱分析方法,采用硅胶Ｇ板为吸附剂,苯：丙酮：水（３：１７．５：４）为展开剂,碘蒸气显色,卡铂的Ｒｆ值为０．４５±０．０３,杂质二碘二氨合铂（Ⅱ）、１,１－环丁二羧酸银及水解产物的Ｒｆ值分别为０．８３±０．０２、０．００和０．００,最小检出限量分别为０．２４、０．２０和０．０２μｇ,本法分离效果好、操作简便、灵敏、快速。     

Binding and conformation of dendrimer-based drug delivery systems:a molecular dynamics study

All atomistic molecular dynamics simulations were performed on poly(amidoamine)(PAMAM) dendrimers that compound non-covalently with anticancer drug molecules including DOX,MTX,CE6,and SN38.The binding energies as well as their associated interaction energies and deformation energies were combined to evaluate the relative binding strength among drug,PAMAM,and PEG chains.We find that the deformation of dendrimers due to drug loading plays a crucial role in the drug binding.It is energetically favorable for the drug molecules to bind with PAMAM while the drugs bind with PEG metastable chains via kinetic confinement.Surface PEGylation helps dendrimers to accommodate more drug molecules with greater strength without inducing too much expansion.This work indicates that tuning the functionalized terminal groups of dendrimers is critical to design efficient dendrimer-based drug delivery systems.     

Functional peptides derived from rice bran proteins

Rice bran has been predominantly used in the feed industry, and only recently it has attracted greater attention in terms of human nutrition with increasing knowledge of its bioactivity. A growing interest is the analysis of physiologically active peptides derived from rice bran proteins. In this paper, the bioactivities of rice bran proteins hydrolysates and peptides are reviewed based on recent studies. These enzymatic hydrolysates and peptides exert various biological activities including antioxidant, antidiabetic, anticancer and inhibitory activity for angiotensin converting enzyme (ACE), which may ultimately prevent certain chronic diseases. Nevertheless, these functionalities can be highly associated with their corresponding structural characteristics, in particular specific sequences and molecular weight distribution. This article may facilitate the expansion of the prospective applications of the bioactive peptides in a number of fields and provide some clues of the relationship between peptides structure and functionality for future research.     

Development and Characterization of DOPEPEG2000 Coated Oleic Acid Liposomes Encapsulating Anticancer Drugs

Liposomes have been widely investigated as drug carriers for a broad range of anticancer drugs. However, their application as a drug delivery system may be challenging due to low encapsulation of active ingredient and poor stability which leads to uncontrolled delivery of bioactive ingredients. The present study aims at incorporating 1,2‐dioleoyl‐sn‐glycero‐3‐phosphoethanolamide‐N‐[methoxy(polyethylene glycol)‐2000 (DOPEPEG2000) into oleic acid (OA) liposomes in order to prolong the lifetime in blood circulation. The pH transition curve of oleic was obtained by titration of sodium oleate solution with 0.05 mol dm^?3 HCl to determine the region where liposomes were abundantly present. The critical vesicle concentration (CVC) was then determined by surface tension measurements. Dry lipid liposomes were hydrated with phosphate buffer at just over twice the CVC value. Optical polarizing microscopy (OPM) showed the presence of liposomes while transmission electron microscopy (TEM) confirmed that the liposomes prepared were spherical in shape and less than 200 nm in size. The incorporation of DOPEPEG2000 into the oleic acid liposomes reduced the average particle size and zeta potential to mimic the red blood cells. The encapsulation efficiency of various anticancer drugs was more than 60% while more than 20% of the drugs were released after 24 h. The results suggest that DOPEPEG2000: oleic acid at a molar ratio of 1:50 fulfilled the requirements for intravenous drug delivery.     

Cladonia lichens and their major metabolites as possible natural antioxidant,antimicrobial and anticancer agents

The aim of this study is to investigate in vitro antioxidant, antimicrobial, and anticancer activities of the acetone extracts of the lichens Cladonia furcata, Cladonia pyxidata and Cladonia rangiferina and their atranorin and fumarprotocetraric acid constituents. Antioxidant activity was evaluated by free radical scavenging, superoxide anion radical scavenging, reducing power, and determination of total phenolic and flavonoid compounds. As a result of the study atranorin had largest free radical scavenging activity with IC₅₀ values 131.48 μg/mL. Moreover, the tested samples had effective reducing power and superoxide anion radical scavenging. Total content of phenol and flavonoid in extracts was determined as pyrocatechol equivalent, and as rutin equivalent, respectively. The strong relationships between total phenolic and flavonoid contents and the antioxidant effect of tested extracts were observed. The antimicrobial activity was estimated by determination of the minimal inhibitory concentration by the broth microdilution method. The most active was fumarprotocetraric acid with minimum inhibitory concentration values ranging from 0.031 to 0.125 mg/mL. Anticancer activity was tested against FemX (human melanoma) and LS174 (human colon carcinoma) cell lines using MTT method. All samples were found to be strong anticancer activity toward both cell lines with IC₅₀ values ranging from 10.97 to 41.23 μg/mL.     

The inhibitory effect of helenalin on telomerase activity is attributed to the alkylation of the CYS445 residue: Evidence from QM/MM simulations

Enhanced telomerase activity is a hallmark in the majority of cancer cells. Thus, understanding the interactions between telomerase and its inhibitors is fundamentally important for the development of novel anticancer drugs without severe side effects. In this study, the covalent binding of helenalin to CYS445 of telomerase (PDB ID: 3DU6) was simulated using combined quantum chemical and molecular mechanical (QM/MM) methods. The results showed that the reaction was a reversible Michael-type addition and a hydrogen bond was formed between helenalin and the side chain of LYS416 of telomerase during the reaction procedure. The LYS416 residue is vital to telomere DNA recognition by interacting with DNA base through hydrogen bonds. The alkylation of CYS445 of telomerase by helenalin may interfere with the telomere DNA recognition at the telomerase active site, thus resulting in inhibition of the enzyme activity.     

Anticancer Activity and Mechanism of Action Evaluation of an Acylhydrazone Cu(II) Complex toward Breast Cancer Cells,Spheroids, and Mammospheres

The purpose of this work was to screen the anticancer activity and mechanisms of action of Cu(II)-acylhydrazone complex [Cu(HL)(H₂O)](NO₃)⋅H₂O, (CuHL), to find a potential novel agent for breast chemotherapies. Cytotoxicity studies on MCF7 cells demonstrated that CuHL has stronger anticancer properties than cisplatin over breast cancer cell models. Computational simulations showed that CuHL could interact in the minor groove of the DNA dodecamer, inducing a significant genotoxic effect on both cancer cells from 0.5 to 1 μM. In this sense, molecular docking and molecular dynamics simulations showed that the compound could interact with 20S proteasome subunits. Also, cell proteasome experiments using breast cancer cells revealed that the complex can inhibit proteasomal activity. Moreover, CuHL induced apoptosis in breast cancer cells at very low micromolar concentrations (0.5–2.5 μM) and displayed relevant anticancer activity over spheroids derived from MCF7 cells. Ultimately, CuHL diminished the number of mammospheres formed, disturbing their morphology and size.