Thermodynamic Studies of Interactions between Sertraline Hydrochloride and Randomly Methylated β-Cyclodextrin Molecules Supported by Circular Dichroism Spectroscopy and Molecular Docking Results

The interaction between sertraline hydrochloride (SRT) and randomly methylated β-cyclodextrin (RMβCD) molecules have been investigated at 298.15 K under atmospheric pressure. The method used—Isothermal Titration Calorimetry (ITC) enabled to determine values of the thermodynamic functions like the enthalpy (ΔH), the entropy (ΔS) and the Gibbs free energy (ΔG) of binding for the examined system. Moreover, the stoichiometry coefficient of binding (n) and binding/association constant (K) value have been calculated from the experimental results. The obtained outcome was compared with the data from the literature for other non-ionic βCD derivatives interacting with SRT and the enthalpy-entropy compensation were observed and interpreted. Furthermore, the connection of RMβCD with SRT was characterized by circular dichroism spectroscopy (CD) and complexes of βCD derivatives with SRT were characterized through the computational studies with the use of molecular docking (MD).

Preclinical Screening of Antidepressant Activity of Formulated Sertraline Hydrochloride-Loaded Solid Lipid Nanoparticles in Rats

Objective: The main goal of our study was to investigate the antidepressant activity of Formulated Sertraline hydrochloride-loaded Solid Lipid Nanoparticles (SLNPs) by using a rat forced swimming test (FST) and tail suspension test (TST). Materials and Methods: Animals were divided into three groups, consisting of six rats in each group. Out of these, one group served as control that received distilled water, second group was standard received Sertraline HCl (20 mg/kg intranasal) and third group was received test formulation (SLNPs 50 mg/kg intranasal). To assess the effect of SLNPs on immobility activity through FST and TST were used to take as a measure of antidepressant activity. Results: SLNPs reduced the immobility duration in TST as well as in FST. In both methods, there was a statistical significant decrease in immobility of SLNPs group when compared to the control group. Conclusion: The results suggested that SLNPs produced significant antidepressant effect in rats which was comparable with control group and standard Sertraline HCl group animals.

Antidepressant Sertraline Hydrochloride Inhibits the Growth of HER2+ AU565 Breast Cancer Cell Line through Induction of Apoptosis, and Arrest of Cell Cycle

Breast cancer is one the most aggressive cancer worldwide, especially Pakistan due to limited therapeutic options. This study was conducted to repurpose the use of selective serotonin reuptake inhibitors (SSRIs), in the treatment of breast cancers, and merit to pursue drug re-positioning in oncology. Anti-proliferative activity of SSRIs, such as fluoxetine, paroxetine, and sertraline hydrochloride on the growth of AU-565, MCF-7, MDA-MB-231, and BT-474 breast cancer cell lines, along with human fibroblast BJ cells was determined in vitro. Changes in nuclear morphology (DAPI staining), and induction of apoptosis (flow cytometry, and caspase-3 activation) were also studied. Sertraline hydrochloride most effectively inhibited the growth of breast cancer cells in vitro. Therefore, pharmacological mechanism involved in sertraline mediated cell death was investigated in HER2+ AU565 cell line. Enhanced nuclear fragmentation, increased Annexin (+) cells, and caspase-3/7 activation indicated that sertraline-mediated cell death could be a result of BCl2-independent apoptosis as evidenced by expression of Bax, and BCl2 genes. Taken together, our results identified sertraline hydrochloride, as a potential candidate for the treatment of HER2-positive breast cancer. Even though these are in vitro results, this study opens great opportunity in the field of drug repurposing for the development of chemotherapeutic agents.