Proposition of In silico Pharmacophore Models for Malaria: A Review

Abstract

In the field of medicinal chemistry, the concept of pharmacophore refers to the specific region of a molecule that possesses essential structural and chemical characteristics for binding to a receptor and eliciting biological activity. Understanding the pharmacophore is crucial for drug research and development, as it allows the design of new drugs. Malaria, a widespread disease, is commonly treated with chloroquine and artemisinin, but the emergence of parasite resistance limits their effectiveness. This study aims to explore computer simulations to discover a specific pharmacophore for Malaria, providing new alternatives for its treatment. A literature review was conducted, encompassing articles proposing a pharmacophore for Malaria, gathered from the "Web of Science" database, with a focus on recent publications to ensure up-to-date analysis. The selected articles employed diverse methods, including ligand-based and structurebased approaches, integrating molecular structure and biological activity data to yield comprehensive analyses. Affinity evaluation between the proposed pharmacophore and the target receptor involved calculating free energy to quantify their interaction. Multiple linear regression was commonly utilized, though it is sensitive to multicollinearity issues. Another recurrent methodology was the use of the Schrödinger package, employing tools such as the Phase module and the OPLS force field for interaction analysis. Pharmacophore model proposition allows threedimensional representations guiding the synthesis and design of new biologically active compounds, offering a promising avenue for discovering therapeutic agents to combat Malaria.