Microwave-Assisted Functionalization of Multi-Walled Carbon Nanotubes for Biosensor and Drug Delivery Applications.

Microwave-assisted synthetic methods have emerged as a popular technique for surface modification and the functionalization of multi-walled carbon nanotubes (MWCNTs) for diverse drug delivery applications. Microwave-induced functionalization of MWCNTs provides a high functionalization and requires less time than conventional techniques. Microwave methods are simple, fast, and effective for the covalent and noncovalent conjugation of MWCNTs with various biomolecules and polymers. The present review focuses on the synthetic and drug delivery applications of microwave irradiation techniques (MITs) for the functionalization of MWCNTs, using amino acids and other molecular frameworks containing amino groups, vitamins, proteins, epoxy moieties, metal nanoparticles, and polymers.

Classification analysis of fatty acid synthase inhibitors using multialgorithms on topological descriptors and structural fingerprints.

Fatty acid synthase (FASN) is one of the enzymes required for fatty acid biosynthesis and is expressed as low or absent in most normal cells/tissues. However, this enzyme is upregulated in various cancer cells; hence, it can act as an important target to design and develop novel FASN inhibitors for cancer therapy. In the present investigation, a series of structurally diverse compounds that possessed FASN inhibitory activities were subjected to classification analysis using different algorithms such as support vector machine, decision tree, Naïve Bayes and random forest. The physicochemical descriptors and MACCS fingerprints were calculated using PaDEL software, and the WEKA software was utilized for the classification model building. The statistical parameters/confusion matrix calculated from the analysis revealed that the selected models have significant predictive performances. The results showed that the topological properties of the molecules are the main determinant for the activity classification. The key descriptors comprised of hydrogen bonding groups, especially acceptor (nHBAcc, minHBint9, minHBint5 and nwHBa), charge on the topological surface of the molecules (JGI10 & GGI2), ionization potential (GATS5i and GATS1i) and branching and distance between the groups (ETA_Eta_B_RC) are significantly contributed in the classification models. Further, the presence of heteroatoms (MACCSFP82, MACCSFP93 and MACCSFP131), especially nitrogen atom(s) and hydrogen bond acceptor groups (N-N group, NC(=O)N, N-C(=O)), actively contributed to the inhibitory activities. The results concluded that the topological polar properties concentrated in a specific region have significant FASN inhibitory activity. Hence, these results shall be used to develop novel molecules with increased FASN inhibitory activity.

Lysinated Multiwalled Carbon Nanotubes with Carbohydrate Ligands as an Effective Nanocarrier for Targeted Doxorubicin Delivery to Breast Cancer Cells.

Multiwalled carbon nanotubes (MWCNTs) are elongated, hollow cylindrical nanotubes made of sp2 carbon. MWCNTs have attracted significant attention in the area of drug delivery due to their high drug-loading capacity and large surface area. Furthermore, they can be linked to bioactive ligands molecules via covalent and noncovalent bonds that allow for the targeted delivery of anticancer drugs such as doxorubicin. The majority of methodologies reported for the functionalization of MWCNTs for drug delivery are quite complex and use expensive linkers and ligands. In the present study, we report a simple, cost-effective approach for functionalizing MWCNTs with the carbohydrate ligands, galactose (GA), mannose (MA) and lactose (LA), using lysine as a linker. The doxorubicin (Dox)-loaded functionalized MWCNTs were characterized using FT-IR, NMR, Raman, XRD and FE-SEM. The drug-loaded MWCNTs were evaluated for drug loading, drug release and cell toxicity in vitro, in breast cancer cells. The results indicated that the carbohydrate-modified lysinated MWCNTs had greater Dox loading capacity, compared to carboxylated MWCNTs (COOHMWCNTs) and lysinated MWCNTs (LyMWCNTs). In vitro drug release experiments indicated that the carbohydrate functionalized LyMWCNTs had higher Dox release at pH 5.0, compared to the physiological pH of 7.4, over 120 h, indicating that they are suitable candidates for targeting the tumor microenvironment as a result of their sustained release profile of Dox. Doxorubicin-loaded galactosylated MWCNTs (Dox-GAMWCNTs) and doxorubicin loaded mannosylated MWCNTs (Dox-MAMWCNTs) had greater anticancer efficacy and cellular uptake, compared to doxorubicin-loaded lactosylated MWCNTs (Dox-LAMWCNTs) and pure Dox, in MDA-MB231 and MCF7 breast cancer cells. However, neither the ligand conjugated multiwall blank carbon nanotubes (GAMWCNTs, MAMWCNTs and LAMWCNTs) nor the lysinated multiwalled blank carbon nanotubes produced significant toxicity in the normal cells. Our results suggest that sugar-tethered multiwalled carbon nanotubes, especially the galactosylated (Dox-GAMWCNTs) and mannosylated (Dox-MAMWCNTs) formulations, may be used to improve the targeted delivery of anticancer drugs to breast cancer cells.

In silico based structural analysis of some piperidine analogs as farnesyltransferase inhibitors.

In silico based QSAR and pharmacophore analyses of a series of piperidine derivatives were performed in order to investigate the structural features of the derivatives responsible for FTase inhibitory activity. The results derived from the QSAR analysis show that the FTase inhibitory activity mediated by the vdW surface area features such as partial charge (PEOE_VSA and Q_VSA) and v_surf (hydrophobic integy moment) of the molecules. The positive contribution of the partial charge descriptors such as Q_VSA_FPNEG and PEOE_VSA-4 reveal that the fractional negative charge on the vdW surface of the molecules and the aqueous solubility (LogS) of the molecules are important for the FTase inhibitory activity. While the hydrophobic integy moment reveals that a clear separation between the hydrophobic and the hydrophilic region in the molecules is important with electrostatic groups (fractional negative charge) for better activity. The pharmacophore analyses of the piperidine derivatives also show that the aromatic, acceptor and donor groups on the molecule favorable for the FTase inhibitory activity.

Synthesis, biological evaluation and in silico metabolic and toxicity prediction of some flavanone derivatives.

Flavones chemically are anthoxanthins, occur either in the free state or as glycosides associated with tannins (flavanoids). Flavanoids (derivatives of flavone) possess various pharmacological activities and due to its xanthine-oxidase enzyme inhibitory effect it also has superoxide-scavenging activities. A series of 2-phenyl-2,3-dihydrochromon-4-one derivatives (flavanone derivatives) were synthesized from chalcones by cyclization method and their activities were evaluated against some gram positive and gram-negative bacteria. IR, NMR and CHN analysis confirmed the structure of the synthesized compounds. The results of the antibacterial studies shows that compounds 2b, 2e, 2f and 2h possess activity against many bacterial strains. Among that the compound (2h) has remarkable activity against all strains viz. 25 microg/ml inhibitory concentration against S. aureus, S. sonnei, E. coli, S. typhimurium and V. cholerae. Compound 2f possess minimum inhibitory concentration of 200 microg/ml against E. coli and S. typhimurium and 25 microg/ml against S. sonnei, S. dysenteriae and V. cholerae. In silico metabolic and toxicity study of the synthesized compounds were performed and the predicted result showed that the compound having hydroxyl functional group undergo sulfate and O-glucuronide conjugation reaction and methoxy derivatives undergo demethylation reaction. The biologically active compounds are free of toxicity in oncogene, teratogen, sensitivity and immunotoxicity.