In Silico Study: Combination of α-Mangostin and Chitosan Conjugated with Trastuzumab against Human Epidermal Growth Factor Receptor 2

Abstract

Breast cancer is a type of cancer with the highest prevalence worldwide. Almost 10–30% of breast cancer cases are diagnosed as positive for HER2 (human epidermal growth factor receptor 2). The currently available treatment methods still exhibit many shortcomings such as a high incidence of side effects and treatment failure due to resistance. This in silico study aims to simulate α-mangostin and chitosan combination conjugated to trastuzumab formulation against HER2 as an effort to improve breast cancer patient therapy. This molecular docking simulation was done through using PatchDock Server. The materials used including the two-dimensional structure of α-mangostin, chitosan, and sodium tripolyphosphate from the PubChem database; trastuzumab FASTA sequence from the DrugBank database; and HER2 structure obtained from a crystal complex with PDB ID: 1N8Z. The results indicated that the particle of α-mangostin and chitosan combinations interacted mostly with the crystallizable fragment (Fc region) of trastuzumab in the conjugation process. The conjugation of trastuzumab to the particle of a combination of α-mangostin and chitosan resulted in the greatest increase in the binding score of the smallest-sized particles (50 Å) with an increase in the score of 3828 and also gave the most similar mode of interaction with trastuzumab. However, the conjugation of trastuzumab eliminated the similarity of the mode of interaction and increased the value of atomic contact energy. Thus, a cominbation of α-mangostin and chitosan conjugated to a trastuzumab formulation was predicted can increase the effectiveness of breast cancer therapy at a relatively small particle size but with the consequence of decreasing atomic contact energy.

Gene expression and anticancer evaluation of Kigelia africana (Lam.) Benth. Extracts using MDA-MB-231 and MCF-7 cell lines

“…These genes and proteins are clinically significant in cancer diagnosis, prognosis, and treatment. Research on how these genes and proteins are expressed and regulated may provide important insights into cancer biology and thereby aid the development of advanced diagnostic and therapeutic options [ 48 ]. It is not reported earlier in the literature whether EKA extract regulates the mRNA expression of TP53 and BCL2 genes or not.…”

Molecular Docking Simulation of Phenolics towards Tyrosinase, Phenolic Content, and Radical Scavenging Activity of Some Zingiberaceae Plant Extracts

“…The 2D structures of the ligands (ethyl p-methoxycinnamate, 6-gingerol, galangin, and kaempferol) and standard ligands (arbutin, kojic acid, and hydroquinone) were built using ChemDraw 12.0 and saved in .cdx format. The geometry optimization of the ligands was performed by applying the molecular mechanic 2 (MM2), and the optimized ligands were saved in .pdb format [34,35].…”

Chitosan/Alginate-Based Nanoparticles for Antibacterial Agents Delivery

“…Nanotechnology emerges as a leading solution to address the challenge of low drug solubility in water. [18][19][20][21] Among the array nano-delivery systems available, polymeric nanoparticles stand out with additional advantages. Beyond enhancing drug solubility, polymeric nanoparticles provide excellent stability during storage and distribution through the bloodstream.…”