Quantitative structure-activity relationship and machine learning studies of 2-thiazolylhydrazone derivatives with anti-Cryptococcus neoformans activity

• Published in: Journal of biomolecular structure & dynamics 2022-01, Vol.40 (20), p.9789-9800
• Main Authors: Fernandes, Philipe de Oliveira, Martins, João Paulo A., de Melo, Eduardo B., de Oliveira, Renata Barbosa, Kronenberger, Thales, Maltarollo, Vinícius Gonçalves
• Format: Article
• Language: English
• Subjects: 2D-QSAR; 4D-QSAR; Antifungal agents; Antifungal Agents - chemistry; Antifungal Agents - pharmacology; Cryptococcus neoformans; Humans; ligand-based drug design (LBDD); Machine Learning; QSAR; Quantitative Structure-Activity Relationship; random forest; thiazolylhydrazones
• ISSN: 0739-1102; 1538-0254
• DOI: 10.1080/07391102.2021.1935321

Cryptococcus neoformans is a fungus responsible for infections in humans with a significant number of cases in immunosuppressed patients, mainly in underdeveloped countries. In this context, the thiazolylhydrazones are a promising class of compounds with activity against C. neoformans. The understanding of the structure-activity relationship of these derivatives could lead to the design of robust compounds that could be promising drug candidates for fungal infections. Specifically, modern techniques such as 4D-QSAR and machine learning methods were employed in this work to generate two QSAR models (one 2D and one 4D) with high predictive power (r 2 for the test set equals to 0.934 and 0.831, respectively), and one random forest classification model was reported with Matthews correlation coefficient equals to 1 and 0.62 for internal and external validations, respectively. The physicochemical interpretation of selected models, indicated the importance of aliphatic substituents at the hydrazone moiety to antifungal activity, corroborating experimental data. Communicated by Ramaswamy H. Sarma