Predictive Modelling of Natural Medicinal Compounds for Alzheimer disease Using Machine Learning and Cheminformatics

TL;DR

This paper presents a machine learning framework using cheminformatics to predict neuroprotective activity of natural compounds for Alzheimer disease, aiding early drug discovery.

Contribution

It introduces an ensemble machine learning approach with feature importance analysis to identify key molecular descriptors influencing activity.

Findings

Random Forest achieved the highest predictive accuracy.

Lipophilicity, molecular weight, and polarity are key descriptors.

The approach reduces costs and time in neurodegenerative drug discovery.

Abstract

Alzheimer disease (AD) is a neurodegenerative disease that lacks specific treatment options. Natural drugs have displayed neuroprotective effects; however, their high-throughput discovery is challenging because of the expense of experimental testing.The study proposed a machine learning approach to identify the anti-dementia activity of natural compounds based on molecular descriptors obtained from cheminformatics. The study used a set of active and inactive compounds obtained from public databases like ChEMBL and PubChem. Various molecular descriptors, including molecular weight, lipophilicity (LogP), topological polar surface area (TPSA), and hydrogen bonding descriptors, were calculated with RDKit. Data preprocessing and feature selection were applied, followed by the development of several classification models (Random Forest, XGBoost, Support Vector Machines, Logistic Regression) and their evaluation based on accuracy, precision, recall, F1-score and ROC-AUC. The outcome suggests that ensemble techniques, such as Random Forest, delivered the best predictive accuracy and ROC-AUC values. This study also highlights that critical physicochemical descriptors in particular lipophilicity, molecular weight and polarity are important in driving neuroprotective activity as identified by feature importance analysis. The integrated machine learning approach shows the potential of combining natural product research and machine learning in early drug discovery for dementia. They provide a means of rapidly exploring large datasets and selecting candidates for experimental confirmation, thus minimising costs and time in the development of drugs for neurodegenerative diseases.