Virtual screening and library enumeration of new hydroxycinnamates based antioxidant compounds: A complete framework

• DOI: 10.1016/j.jscs.2023.101670
• Publication Date: 2023-06-07T23:51:01Z
• Authors: Jameel Ahmed Bhutto; Tayyaba Mubashir; Mudassir Hussain ...; Hafsa; Farooq Ahmad; Shaban R.M. Sayed; Hosam O. El-ansary; Muhammad Ishfaq
• Keywords: Chemistry; Inverse design; Cheminformatics; Machine learning; QD1-999; 01 natural sciences; Antioxidants; 0104 chemical sciences

Designing of molecules for drugs is important topic from many decades. The search of new drugs is very hard, and it is expensive process. Computer assisted framework can provide the fastest way to design and screen drug-like compounds. In present work, a multidimensional approach is introduced for the designing and screening of antioxidant compounds. Antioxidants play a crucial role in ensuring that the body's oxidizing and reducing species are kept in the proper balance, minimizing oxidative stress. Machine learning models are used to predict antioxidant activity. Three hydroxycinnamates are selected as standard antioxidants. Similar compounds are searched from ChEMBL database using chemical structural similarity method. The libraries of new compounds are generated using evolutionary method. New compounds are also designed using automatic decomposition and construction building blocks. The antioxidant activity of all designed and searched compounds is predicted using machine learning models. The chemical space of searched and generated compounds is envisioned using t-distributed stochastic neighbor embedding (t-SNE) method. Best compounds are shortlisted, and their synthetic accessibility is predicted to further facilitate the experimental chemists. The chemical similarity between standard and selected compounds is also studied using fingerprints and heatmap.