Facile Design of Superparamagnetic Core-Shell EDC-Ascorbate-Fe3O4 Nanocomposites for Targeted Delivery of Doxorubicin to Triple Negative Breast Tumor by Fenton Reaction

Triple negative breast cancer (TNBC) phenotype accounts for its significant resistance to chemotherapy and other therapeutic procedures. So, the establishment of better and effective therapeutic procedures has become a challenge during recent years. Doxorubicin is a potent chemotherapeutic candidate but its prominent side effects can be subsided via its combination with nanocarriers. So, the present study was aimed to design ascorbic acid modified biopolymeric EDC/NHS-modified magnetic nanoparticles (MNP@MNP@AA-EDC/NHS-DOX for doxorubicin drug delivery to the triple negative breast cancers cell lines of MDA-MB-231, MDA-MB-468 and HCC1937. Monodisperse Fe3O4 MNPs were prepared by chemical co-precipitation method. According to the SEM and DLS results, MNP@AA-EDC/NHS-DOX, MNPs@AA, MNP@AA-MNP@AA-EDC/NHS and MNP@AA-EDC/NHS-DOX had average particle diameter of 53, 79 and 95 nm, respectively. While, XRD analysis showed that the MNP material had the strongest Fe crystal peak, while surface modified MNP@AA-EDC/NHS-DOX did not alter the characteristic properties of MNPs. VSM magnetization analysis revealed that MNP@AA-EDC/NHS-DOX exhibited sufficient paramagnetic potential in the presence of external magnetic field. The TG analysis showed that thermal decomposition capacity of present nanocomposites was: MNPs > MNP@AA-EDC/NHS > AA-MNPs > MNP@AA-EDC/NHS-DOX. AA-modified MNPs did not completely lose their thermal stability as compared to other modifications. Alamar blue analysis revealed that the bare MNPs did have non-significant cytotoxicity in MDA-MB-231, MDA-MB-468 and HCC1937 cell lines (p > 0.001). While, MNP@AA-EDC/NHS-DOX at 0.1, 1.0 and 10 μg/mL DOX concentrations showed significantly lowered cell survival percentages as compared to the free DOX regimens after 24 and 72h. While, HCC1937 cell line had the most accumulation of free (1.42 > 0.93 > 0.9 pg DOX/cell) and conjugated DOX (2.64 > 2.2 > 1.91 pg DOX/cell) after 6 h of incubation period as compared to MDA-MB-468 and MDA-MB-231, respectively (* p < 0.05). Present results provide a new insight into the design of paramagnetic targeted drug delivery nanocomposite system to overcome the obstacles and side effects of conventional chemotherapeutic agents

Asymmetric Hsp90 N domain SUMOylation recruits Aha1 and ATP-competitive inhibitors

The stability and activity of numerous signaling proteins in both normal and cancer cells depends on the dimeric molecular chaperone heat shock protein 90 (Hsp90). Hsp90's function is coupled to ATP binding and hydrolysis and requires a series of conformational changes that are regulated by cochaperones and numerous posttranslational modifications (PTMs). SUMOylation is one of the least-understood Hsp90 PTMs. Here, we show that asymmetric SUMOylation of a conserved lysine residue in the N domain of both yeast (K178) and human (K191) Hsp90 facilitates both recruitment of the adenosine triphosphatase (ATPase)-activating cochaperone Aha1 and, unexpectedly, the binding of Hsp90 inhibitors, suggesting that these drugs associate preferentially with Hsp90 proteins that are actively engaged in the chaperone cycle. Importantly, cellular transformation is accompanied by elevated steady-state N domain SUMOylation, and increased Hsp90 SUMOylation sensitizes yeast and mammalian cells to Hsp90 inhibitors, providing a mechanism to explain the sensitivity of cancer cells to these drugs. © 2014 Elsevier Inc

Novel fluoro substituted benzo[b]pyran with anti-lung cancer activity

1887-18936-Fluorobenzo[b]pyran-4-one 1 on condensation with aromatic aldehydes yields 3-arylmethylene-6-fluoro-2,3-dihydrobenzo[b]pyran-4-ones 2 which on treatment with phenylhydrazine and thiourea gives the pyrazole and pyrimidine thione derivatives 3 and 4, respectively. Compound 4 reacts with chloroacetic acid in acetic acid-acetic anhydride mixture to afford the thiazolopyrimidines 5 which on condensation with aromatic aldehyde furnish the corresponding arylmethylene­thiazolopyrimidine derivatives 6. The product 6 could be prepared directly by the action of chloroacetic acid and the proper aldehyde on 4 in the presence of acetic acid-acetic anhydride mixture. Product 2 reacts with malononitrile in the presence of ammonium acetate or piperidine to afford the pyridine- and pyran- 7 and 8 derivatives, respectively. Also, compound 1 on treatment with arylmethylenecyanoacetamide yields the pyridone derivatives 9. Condensation of 1 with malononitrile affords the yliedinemalononitrile 10, which on reaction with p-chlorobenzaldehyde-ammonium acetate or arylmethylene-cyano­acetamide yields the pyridine derivative 11 (isomer of 8) and the dicarbonitrile derivative 12, respectively. The synthesized compounds have been tested against three cell lines of human cancer (lung, breast and CNS cancer), and these compounds show anticancer activity at low concentration as compared to reference drug 5-fluorodeoxyuridine

Theoretical Investigation of the Effect of (8,0) Single-walled Carbon Nanotubes on Acidity of Aliphatic Alcohols

ONIOM calculation is carried out to estimate the acidity of five aliphatic alcohols before and after adsorbing on the tip of (8,0) singlewalled carbon nanotube. The ONIOM method is performed using a combination of density functional theory and AM1 semiemperical method for alcohols and their corresponding conjugated bases. Deprotonation Gibbs free energies of alcohols are calculated and compared before and after adsorbing on the nanotube. Solute-solvent interactions are taken into account by employing the conductor polarized continuum model (CPCM). The results show that the acidity of alcohols change after adsorbing on the nanotubes and these alcohols have a little effect on (8,0) SWCNT

Adsorption of formamide on pure, Al-, N-doped, and Al/N co-doped (8, 0) single-wall carbon nanotubes: a DFT study

This study investigates the sensing capabilities of (8,0) SWCNTs in detecting formamide (HCONH2), a molecule crucial for the structure of proteins, nucleic acids, and certain anti-cancer drugs. Adsorption of HCONH2 on pristine SWCNT, Al- and N-doped SWCNT, and Al/N co-doped SWCNT was studied using dispersion-corrected density functional theory (DFT-D). Formamide was adsorbed from both oxygen and –NH2 sides, and the structures were fully optimization. The relaxed structures were applied for calculating magnetic and electronic properties like adsorption energies, band structures, and partial density of states. Most negative adsorption energy in doped structures indicates the strongest adsorption of formamide in doped structures than pristine SWCNT. The results also indicates that formamide adsorption does not change the electronic properties of pure SWCNT and N-doped SWCNT. However, it removes the band gaps of Al- and Al/N-doped SWCNT. Therefore, the modified nanotubes convert from semiconductor to metallic character which can be detected using electronic devices. Moreover, formamide adsorption induces some magnetization to Al-doped SWCNT and Al/N co-doped which can be utilized in spin transport devices. These findings suggest that Al/N co-doped and Al-doped SWCNTs are good candidates for detecting HCONH2 molecules

Electronic and Optical Properties of SnGe and SnC Nanoribbons: A First-Principles Study

Structural, electronic, and optical properties of one-dimensional (1D) SnGeand SnC with two types (armchair and zigzag) and different widths are studied by usingfirst-principles calculations. The atoms of these structures in edges are passivated byhydrogen. The results show armchair SnGe and SnC nanoribbons (A-SnXNRs, X=Ge, C)are the direct semiconducting and divided into three distinct families W=3p, W=3p+1,and W=3p+2, (p is a positive integer). By increasing width, the band gaps converge to1.71 eV and 0.15 eV for A-SnCNRs and A-SnGeNRs, respectively. Furthermore, theposition of the first peak of the dielectric function in both of them occurs in their value ofdirect band gap at أ point. also, the absorption coefficient for 9, 11, 13 A-SnCNRsdisplays that there is no absorption at the lower energy range from 0 to 1.2 eV, whereasabsorption characteristics for 9, 11, and 13 A-SnGeNRs appeared at near-infrared to thevisible spectrum. These results can provide important information for the use of GroupIV binary compounds in electronic devices

Tenofovir-tethered gold nanoparticles as a novel multifunctional long-acting anti-HIV therapy to overcome deficient drug delivery-: an in vivo proof of concept

Abstract Background The adoption of Antiretroviral Therapy (ART) substantially extends the life expectancy and quality of HIV-infected patients. Yet, eliminating the latent reservoirs of HIV to achieve a cure remains an unmet need. The advent of nanomedicine has revolutionized the treatment of HIV/AIDS. The present study explores a unique combination of Tenofovir (TNF) with gold nanoparticles (AuNPs) as a potential therapeutic approach to overcome several limitations of the current ART. Results TNF-tethered AuNPs were successfully synthesized. Cell viability, genotoxicity, haemolysis, and histopathological studies confirmed the complete safety of the preparation. Most importantly, its anti-HIV1 reverse transcriptase activity was ~ 15 folds higher than the native TNF. In addition, it exhibited potent anti-HIV1 protease activity, a much sought-after target in anti-HIV1 therapeutics. Finally, the in vivo biodistribution studies validated that the AuNPs could reach many tissues/organs, serving as a secure nest for HIV and overcoming the problem of deficient drug delivery to HIV reservoirs. Conclusions We show that the combination of TNF and AuNPs exhibits multifunctional activity, viz . anti-HIV1 and anti-HIV1 protease. These findings are being reported for the first time and highlight the prospects of developing AuNP-TNF as a novel next-generation platform to treat HIV/AIDS. Graphical Abstrac

Ambulatory blood pressure monitoring in children and adolescents with type-1 diabetes mellitus and its relation to diabetic control and microalbuminuria

Diabetes mellitus (DM) is now considered as the major cause of end-stage kidney failure, and hypertension (HTN) is one of the main determinants of progression of renal disease. The aim of this study was to assess the role of blood pressure (BP) by ambulatory blood pressure monitoring (ABPM) in children and adolescents with type-1 DM and its correlation with micro-albuminuria (MA) and diabetic control. Eighty-one patients with type-1 DM (mean age 13 ± 4 years), whose duration of DM was at least two years, were enrolled in this study. The prevalence of HTN based on ABPM was 28.4%, while by casual method it was 32.1%. The pattern of HTN was as follows: mean systolic HTN 27.2%, mean diastolic HTN 11.2%, daytime systolic HTN 17.3%, daytime diastolic HTN 6.2%, night systolic HTN 30.9%, and night diastolic HTN 29.7%. The systolic and diastolic BP loads were 33.4 and 27.2%, respectively. About 70.4% of the patients were non-dippers, 12.4% had masked HTN, and 3.7% had white coat HTN. The pre-valence of MA was 34.6% and that of abnormal HbA 1 c was 82.7%. There was no correlation bet-ween HTN and both MA and HbA 1 c; also, no correlation was found between the duration of dia-betes and HbA 1 c. Moreover, no significant correlation was found between the duration of diabetes and MA (P = 0.080). Despite the high prevalence of abnormal BP profile among diabetic children, prospective longitudinal studies considering the other major risk factors, particularly genetic factors, which have an impact on the progression to diabetic nephropathy, are recommended

Moller-Plesset perturbation theory calculations of the pK(a) values for a range of carboxylic acids

This work presents calculated values of the pK for a series of carboxylic acids spanning a wide range of acidities, using quantum mechanical treatment of solute electronic structure in conjunction with a dielectric continuum model for solvation. The calculations are carried out using 3rd order Møller-Plesset perturbation theory. Solute-solvent interactions have been taken into account by employing the polarizable continuum model (PCM). The calculated pK values are in significantly better agreement with experimental data for the majority of the acids studied than other recently published results. The mean absolute deviation of the calculated pK values is 0.68 in pK units, for the carboxylic acids considered

Synthesis and anti-cancer activity of pyridine and thiazolopyrimidine derivatives using 1-ethylpiperidone as a synthon

213-2213,5-Bisarylmethylene-1-ethylpiperidone 2 on reaction with thiourea yield the thioxopyri midine derivatives 3, which on condensation with bromoacetic acid, 2-bromopropanoic acid or 3-bromopropanoic acid afford thiazolopyrimidine 4, 2-methyl-thiazolopyrimidines 5 and thiazinopyrimidine derivatives 6, respectively. Compounds 7 and 8 are also obtained via condensation of compounds 3 with 3-chloropentan-2, 4-dione, bromoacetic acid and aromatic aldehydes, respectively. However, compounds 8 are prepared directly by condensation of compounds 4 with aromatic aldehydes. Compounds 2 on condensation with malononitrile in ethanol/piperidine or acetic acid/ammonium acetate mixture give pyridopyran 9 and pyridopyridine 10, respectively. Also compound 10 could be prepared directly from compound 9. Compounds 2 when condensed with phenylhydrazine, ethyl cyanoacetate or guanidine hydrochloride yields pyridopyrazole 11, pyridopyridone 12 and pyridoaminopyrimidine derivatives 13, respectively