Vanadocene-functionalized mesoporous silica nanoparticles: platforms for the development of theranostic materials against breast cancer.

Nanoscale materials have demonstrated a very high potential in anticancer therapy by properly adjusting their functionalization and physicochemical properties. Herein, we report the synthesis of some novel vanadocene-loaded silica-based nanomaterials incorporating four different S-containing amino acids (penicillamine, methionine, captopril, and cysteine) and different fluorophores (rhodamine B, coumarin 343 or Alexa Fluor™ 647), which have been characterized by diverse solid-state spectroscopic techniques viz; FTIR, diffuse reflectance spectroscopies,13C and51V solid-state NMR spectroscopy, thermogravimetry and TEM. The analysis of the biological activity of the novel vanadocene-based nanostructured silicas showed that the materials containing cysteine and captopril aminoacids demonstrated high cytotoxicity and selectivity against triple negative breast cancer cells, making them very promising antineoplastic drug candidates. According to the biological results it seems that vanadium activity is connected to its incorporation through the amino acid, resulting in synergy that increases the cytotoxic activity against cancer cells of the studied materials presumably by increasing cell internalization. The results presented herein hold significant potential for future developments in mesoporous silica-supported metallodrugs, which exhibit strong cytotoxicity while maintaining low metal loading. They also show potential for theranostic applications highlighted by the analysis of the optical properties of the studied systems after incorporating rhodamine B, coumarin 343 (possible)in vitroanticancer analysis, or Alexa Fluor™ 647 (in vivostudies of cancer models).

Ligand-based design of chalcone analogues and thermodynamic analysis of their mechanism of free radical scavenge.

Overproduction of free radicals in the body may result in oxidative stress, which plays an active role in the development of various health disorders. Consequently, the development of efficient free radical scavengers and evaluation of their antioxidant properties is a research area of interest. In the present research, computational quantum chemical approach based on the density functional theory (DFT) method was employed to elucidate the free radical scavenge of chalcone derivatives via thermodynamic studies. New set of chalcone antioxidants were designed. Their reactivity towards hydroperoxyl (HOO·) and methyl peroxyl (CH3OO·) radicals were investigated through systematic study of their mechanism of free radical scavenge. Various reaction enthalpies and Gibbs free energy that characterize the various steps in these mechanisms were computed in the gas phase and aqueous solution, in order to identify the main channels of reaction. Results in the gas phase indicate that hydrogen atom transfer (HAT) and sequential proton loss electron transfer (SPLET) mechanisms represent the most plausible reaction pathways, while single electron transfer followed by proton transfer (SET-PT) mechanism was thermodynamically unfeasible. However, these mechanisms were thermodynamically favoured in aqueous solution. Also, these chalcone derivatives were observed to be more effective in scavenging HOO· than CH3OO· radicals in both phases. Based on the exergonicity of the obtained results, the molecule MCHM 17 ((E)-1-(3-bromo-5-hydroxyphenyl)-3-(2,5-dihydroxyphenyl)prop-2-en-1-one) at the 5-OH site was found to exhibit the greatest potential to scavenge HOO· and CH3OO· radicals in both phases. This research is a gateway to the efficient exploitation of these compounds in pharmacy and food chemistry.

Evaluation of the antioxidant properties of curcumin derivatives by genetic function algorithm.

The prevalence of degenerative diseases in recent time has triggered extensive research on their control. This condition could be prevented if the body has an efficient antioxidant mechanism to scavenge the free radicals which are their main causes. Curcumin and its derivatives are widely employed as antioxidants. The free radical scavenging activities of curcumin and its derivatives have been explored in this research by the application of quantitative structure activity relationship (QSAR). The entire data set was optimized at the density functional theory (DFT) level using the Becke's three-parameter Lee-Yang-Parr hybrid functional (B3LYP) in combination with the 6-311G∗ basis set. The training set was subjected to QSAR studies by genetic function algorithm (GFA). Five predictive QSAR models were developed and statistically subjected to both internal and external validations. Also the applicability domain of the developed model was accessed by the leverage approach. Furthermore, the variation inflation factor, (VIF), mean effect (MF) and the degree of contribution (DC) of each descriptor in the resulting model were calculated. The developed models met all the standard requirements for acceptability upon validation with highly impressive results ( R=0.965,R2=0.931,Q2(RCV2)=0.887,Rpred2=0.844,cRp2=0.842s=0.226,rmsep=0.362 ). Based on the results of this research, the most crucial descriptor that influence the free radical scavenge of the curcumins is the nsssN (count of atom-type E-state: >N-) descriptor with DC and MF values of 12.980 and 0.965 respectively.