Ligand-conjugated multiwalled carbon nanotubes for cancer targeted drug delivery.

Multiwalled carbon nanotubes (MWCNTs) are at the forefront of nanotechnology-based advancements in cancer therapy, particularly in the field of targeted drug delivery. The nanotubes are characterized by their concentric graphene layers, which give them outstanding structural strength. They can deliver substantial doses of therapeutic agents, potentially reducing treatment frequency and improving patient compliance. MWCNTs' diminutive size and modifiable surface enable them to have a high drug loading capacity and penetrate biological barriers. As a result of the extensive research on these nanomaterials, they have been studied extensively as synthetic and chemically functionalized molecules, which can be combined with various ligands (such as folic acid, antibodies, peptides, mannose, galactose, polymers) and linkers, and to deliver anticancer drugs, including but not limited to paclitaxel, docetaxel, cisplatin, doxorubicin, tamoxifen, methotrexate, quercetin and others, to cancer cells. This functionalization facilitates selective targeting of cancer cells, as these ligands bind to specific receptors overexpressed in tumor cells. By sparing non-cancerous cells and delivering the therapeutic payload precisely to cancer cells, this therapeutic payload delivery ability reduces chemotherapy systemic toxicity. There is great potential for MWCNTs to be used as targeted delivery systems for drugs. In this review, we discuss techniques for functionalizing and conjugating MWCNTs to drugs using natural and biomacromolecular linkers, which can bind to the cancer cells' receptors/biomolecules. Using MWCNTs to administer cancer drugs is a transformative approach to cancer treatment that combines nanotechnology and pharmacotherapy. It is an exciting and rich field of research to explore and optimize MWCNTs for drug delivery purposes, which could result in significant benefits for cancer patients.

Design and discovery of silybin analogues as antiproliferative compounds using a ring disjunctive - Based, natural product lead optimization approach.

The present study reports the synthesis and anticancer activity evaluation of twelve novel silybin analogues designed using a ring disjunctive-based natural product lead (RDNPL) optimization approach. All twelve compounds were tested against a panel of cancer cells (i.e. breast, prostate, pancreatic, and ovarian) and compared with normal cells. While all of the compounds had significantly greater efficacy than silybin, derivative 15k was found to be highly potent (IC50 < 1 µM) and selective against ovarian cancer cell lines, as well as other cancer cell lines, compared to normal cells. Preliminary mechanistic studies indicated that the antiproliferative efficacy of 15k was mediated by its induction of apoptosis, loss of mitochondrial membrane potential and cell cycle arrest at the sub-G1 phase. Furthermore, 15k inhibited cellular microtubules dynamic and assembly by binding to tubulin and inhibiting its expression and function. Overall, the results of the study establish 15k as a novel tubulin inhibitor with significant activity against ovarian cancer cells.

Comparative structural analysis of α-glucosidase inhibitors on difference species: a computational study.

Structural feature analysis of chlorogenic acid derivatives made up of varying lengths of alkyl groups as α-glucosidases inhibitors were performed by QSAR techniques. The statistically significant models derived from the study were validated by leave one out, Y-randomization and test set methods. The predictive capacity of the models was assessed by its validation parameters such as crossvalidated correlation coefficients (Q(2)), predictive residual analysis and other correlation parameters. The results obtained from the study show that the models were constructed with vsurf like properties (vsurf_ID4, vsurf_ID7 and vsurf_CW8), partial charge (Q_VSA_FNEG) and conformation dependent charged (dipoleX) descriptors. The integy moments of hydrophobicity descriptors (ID4 and ID7) are contributed for the inhibitory activity of the α-glucosidases enzymes of both the species. The vsurf_ID7 descriptor has contributed significantly (negatively) for the inhibitory activity prediction of α-glucosidases enzymes of S. cerevisiae. The partial negative charge on the surface of the molecules is detrimental for the activity, which reveals that the active site of the enzymes may have negatively charged groups. The pharmacophore analysis results also confirm the presence of hydrophilic properties on the vdW surface of the molecules. These results explain that the active sites of α-glucosidase enzymes of both the species have the same environment for the interaction. The alkyl side chain on the molecules is important for the pharmacokinetic behavior of the molecules and reduces the interaction energy of the molecules with the water. Hence, these results will be useful for designing novel molecules with multiple activities.

In silico-based structural analysis of arylthiophene derivatives for FTase inhibitory activity, hERG, and other toxic effects.

In the present investigation, the authors have performed an in silico-based analysis on a series of arylthiophene derivatives for the determination of their structural features responsible for farnesyltransferase (FTase) inhibitory activity, hERG blocking activity, and toxicity by quantitative structure-activity relationship and pharmacophore analysis techniques. The statistically significant models derived through multiple linear regression analysis were validated by different validation methods. The applicability of the descriptors contributed in the selected models show that the polar and polarizable properties on the van der Waals (vdW) surface area of the molecules are important for the FTase inhibitory and hERG blocking activities, while being detrimental for the toxicity of the molecules. It is interesting to note that the topological properties, molecular flexibility, and connectivity of the molecules are positively correlated to all the activities (FTase inhibition, hERG blocking, and toxicity). This implies that the flexibility of the molecules is the common feature for interaction in all targets, whereas the presence of polar groups on the molecular surface (vdW) is a determinant for the favorable (FTase inhibition) or unwanted effect (hERG blocking and toxicity) of the molecules. The pharmacophore analysis of the molecules demonstrated that the aromatic/hydrophobicity and polarizability features are important pharmacophore contours favorable for these activities.