Targeted delivery of a novel anticancer compound anisomelic acid using chitosan-coated porous silica nanorods for enhancing the apoptotic effect, 2015, BIOMATERIALS SCIENCE, (3) Targeted cancer therapies are currently a strong focus in biomedical research. The most common approach is to use nanocarrier-based targeting to specifically deliver conventional anticancer drugs to enhance their therapeutic efficacy, increase bioavailabil ity, and decrease the side-effects on normal cells. A step further towards higher specificity and efficacy would be to employ specific novel drugs along with specific nanocarrier -based targeting. Our recent studies have demonstrated that a plant-derived diterpenoid compound, anisomelic acid (AA), induces apoptosis in cervical cancer cells. In this work, we describe the development of a folic acid (FA)-targeted AA delivery system using chitosan-coated rod-shaped mesoporous silica particles (Chitosan-NR-MSP). The cellular internalization and and uptake enhancement of the FA-Chitosan-NR-MSP towards cancerous folate receptor (FR) -positive (SiHa and HeLa) and/or normal FR-negative (HEK 293) cells were assessed, which indicated that the intracellular uptake of FA-conjugated Chitosan-NR-MSP was more target-specific. Furthermore, the induction of apoptosis by AA-loaded chitosan-coated rod-shaped particles on SiHa cells was studied. By employing caspase activation and PARP cleavage as measure of apoptosis, the FA-particle mediated AA treatment was clearly more effective, significantly enhancing apoptosis in comparison to non-targeted Chitosan-NR-MSP or free AA in SiHa cells, suggesting that the FA-Chitosan-NR-MSPs can be potentially utilized as a drug delivery system for cervical cancer treatment.

The molecular interaction of polymer-anchored cobalt(III) complex, cis-[Co(bpy) 2 (BPEI)Cl]Cl 2 $4H 2 O (bpy ¼ 2,2 0 -bipyridine, BPEI ¼ branched polyethyleneimine) with two plasma proteins, human serum albumin (HSA) and bovine serum albumin (BSA) using various spectrophotomeric techniques has been investigated. The steady-state and time-resolved fluorescence spectra clearly demonstrated the static quenching mechanism. The calculated thermodynamic parameters revealed that the interaction between the polymer-cobalt(III) complex and HSA/BSA was driven mainly by van der Waals forces and hydrogen bonds. The results observed from three dimensional fluorescence and circular dichorism (CD) spectral studies manifested the conformational changes of HSA/BSA upon addition of the polymer-cobalt(III) complex. Furthermore, the antimicrobial result showed that the polymer-cobalt(III) complex exhibits good antibacterial and antifungal activities against certain human pathogenic microorganisms. In addition, the antiproliferative properties of the polymercobalt(III) complex on the HEp-2 human larynx cancer cells were determined using the MTT assay.The mode of cell death induced by the complex following treatment was analyzed adopting specific staining techniques. MTT assay revealed that the viability of the cells thus treated was significantly decreased and the cells succumbed to apoptosis as well as necrosis as reflected in changes in the nuclear morphology and cytoplasmic features by AO & EB and Hoechst staining methods.

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Anisomelic acid (AA) is a macrocyclic cembranolide compound extracted from Anisomeles herbal species. Recently, we have shown that AA possesses both anticancer and antiviral activity. However, to date, the plasma protein binding properties of AA are unknown. Here, we describe the molecular interactions of AA with two serum proteins, human serum albumin (HSA) and bovine serum albumin (BSA), adopting multiple physicochemical methods. Besides, molecular docking and dynamics simulations were performed to predict the interaction mode and the dynamic behavior of AA with HSA and BSA. The experimental results revealed that hydrophobic forces play a significant part in the interaction of AA to HSA and BSA. The outcomes of the principal components analysis (PCA) of the poses based on root-mean-squared distances showed less variation in AA-HSA, opposed to what is seen for BSA-AA. Furthermore, binding free energies estimated for AA-HSA and AA-BSA complexes at different temperatures (298, 303, 308, and 313 K) based on molecular mechanics-generalized Born surface area (MMGBSA) approaches were well correlated with our experimental results.

The vast majority of cervical and 75% of oropharyngeal carcinomas are triggered by infection with a type of high-risk oncogenic human papillomavirus (HPV). It is well-known that E6 and E7 oncoproteins are critical for viral-induced cancer, and hence, they represent valuable targets for therapeutic intervention in HPV-mediated cancers. Our earlier research on the cembranoid, anisomelic acid (AA) showed that, AA has the potential to induce apoptosis in HPV cells by the depletion of E6 and E7 oncoproteins. The present study describes the structure-activity relationship and the evaluation of synthetic AA like compounds, i.e simplified cembranoid-like structures, as HPV inhibitors against some papilloma cell lines. Both from experimental and computational results, we observed that these compounds induced apoptosis by the same E6/E7-based mechanism as AA, but at earlier time points, thus being far more effective than AA. Further, the data indicated that only part of the structure of AA is required for the molecular action. Based on these results, we identified some novel and potential compounds for specific treatment of HPV-associated carcinomas.