Quantitative Structure Activity Relationship (QSAR) Investigations and Molecular Docking Analysis of Plasmodium Protein Farnesyltransferase Inhibitors as Potent Antimalarial Agents
Journal Title: Jordan Journal of Pharmaceutical Sciences - Year 2022, Vol 15, Issue 3
Abstract
The development of farnesyltransferase inhibitors based on the benzophenone scaffold directed against Plasmodium falciparum is considered a strategy in malaria treatment. In this work, quantitative structure–activity relationship (QSAR) was performed to predict the protein farnesyltransferase (PFT) inhibitory activities for a series of 36 benzophenone derivatives. The data set was divided into two subsets of training and test sets, and the best model using multiple linear regression (MLR), with the values of internal and external validity (R2 = 0.884, R2adj = 0.865, R2pred = 0.821, Q2cv =0.822 and R2p=0.811) was found in agreement with the Tropsha and Golbraikh criteria. The applicability domain (AD) was determined using the Williams plot to describe the chemical space for the model used in this study. The model shows that antimalarial activities of benzophenone depend on logP, bpol, MAXDn, and FMF descriptors. These indications prompted us to design new benzophenones PFT inhibitors and predict the value of their anti-malarial activities based on the MLR equation. Docking results reveal that the newly designed benzophenones bind to the hydrophobic pocket and polar contact with high affinity. The predicted results from this study can help to design novel benzophenone as inhibitors of human PFT with high antimalarial activities.
Authors and Affiliations
Mebarka Ouassaf, Salah Belaidi, Amneh Shtaiwi, Samir Chtita
Keywords
Related Articles
- EP ID EP711678
- DOI -
- Views 24
- Downloads 0
Antidiabetic activity, polyphenols-based characterization and molecular interaction of extract of un-ripe pods of Vinca rosea cv. Pink
The study aimed to investigate extracts of un-ripe pods of Vinca rosea cv. Pink for antidiabetic activity and polyphenol-based characterization of extracts using HPLC. Moreover, the molecular interaction of the identifi...
Emergency Research Status in the Middle Eastern Region
Conducting research in emergency settings is paramount to advance knowledge and experiences on dealing with critically ill patients. However, the involvement of highly vulnerable subjects, who are mostly incapable of co...
Development and Validation of HPLC Method for quantification of Zonisamide in Spiked Human Plasma
In present work a simple, economic, accurate and precise HPLC method with UV detection was developed for the quantification of zonisamide (ZON) in spiked human plasma using trimethoprim (TRI) as an internal standard. Bo...
Public Perception of Pharmacist's Role during COVID-19 Outbreak in Jordan
Background: The pandemic COVID-19 requires collaborative teamwork by all healthcare professionals including Pharmacists who could help in combating epidemic diseases by providing several pharmaceutical services. Neverth...
Phytochemical Screening and Pharmacological Evaluation of the Methanolic Extract of Cissus Elongata Roxb. Leaves
This study evaluates the pharmacological activity of the methanolic extract of Cissus elongata Roxb. leaves. Dried leaves of C. elongata were extracted with methanol. The crude extract was then tested to identify the pr...