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Current Computer-Aided Drug Design

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ISSN (Print): 1573-4099
ISSN (Online): 1875-6697

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Research Article

A Computational Investigation on Chitosan Derivatives using Pharmacophore- based Screening, Molecular Docking, and Molecular Dynamics Simulations against Kaposi Sarcoma

Author(s): Kiruba Sakthivel, Priyanka Ganapathy, Kirubhanand Chandrasekaran, Gowtham Kumar Subbaraj and Langeswaran Kulanthaivel*

Volume 20, Issue 3, 2024

Published on: 17 May, 2023

Page: [248 - 263] Pages: 16

DOI: 10.2174/1573409919666230428100646

Price: $65

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Abstract

Background: Cancer is one of the most dangerous illnesses to the human body due to its severity and progressive nature. Kaposi's Sarcoma (KS) tumor can appear as painless purple spots on the legs, foot, or face. This cancer develops in the lining of lymph arteries and blood vessels. Along with the enlargement of lymph nodes, the vaginal region and the mouth portion are the additional target areas of KS. DNA-binding proteins known as Sox proteins are found in all mammals and belong to the HMG box superfamily. They controlled a wide range of developmental procedures, such as the formation of the germ layer, the growth of organs, and the selection of the cell type. Human developmental abnormalities and congenital illnesses are frequently caused by the deletion or mutation of the Sox protein.

Aim: The purpose of this study is to determine the promising Kaposi's sarcoma inhibitors through computational studies.

Objective: In this present study computational approaches were used to evaluate the anti- carcinogenic efficacy against Kaposi's sarcoma.

Methods: Ligand-based pharmacophore screening was performed utilising four different chemical libraries (Asinex, Chembridge, Specs, and NCI Natural products (NSC)) depending on the top hypothesis. The top hits were examined using molecular docking, absorption, distribution, metabolism and excretion. Highest occupied molecular orbital and lowest unoccupied molecular orbital were analysed to determine the lead compounds' biological and pharmacological efficacy. The results of the study indicated that the leading candidates were possible SOX protein inhibitors.

Results: A pharmacophore model to inhibit the production of SOX protein in Kaposi Sarcoma was generated in this computational experiment using a set of 19 Chitosan compounds.

Conclusion: The results revealed that the top hits responded to all of the pharmacological druglikening criteria and had the best interaction residues, fitness scores, and docking scores. The resulting leads might be potential Kaposi's Sarcoma alternative treatments.

Keywords: SOX (Shutoff Exonuclease), pharmacophore hypothesis, virtual screening, MM-GBSA, HOMO-LUMO, molecular docking and dynamic simulations.

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