Developing Correlation Between In Silico Molecular Modeling and In Vitro α‐Amylase, Anti‐Cancer and SARS‐COV‐2 Studies of Bis‐Indole Derived Triazine‐Based Thiazolidinone Hybrid Derivatives

Abstract

In the era of COVID‐19 most of the marketed drugs have been found with some negative effects as well as with fewer numbers in the market. There is a serious need of an anti‐COVID agent which can maintain the normal body function with fewer or no side effects. For this purpose, hybrid derivatives based on bis‐indole derived triazine based thiazolidinone derivatives (1–12) were successfully synthesized and characterized using various spectroscopic techniques including 1H NMR, 13C NMR and HREI‐MS. All the synthesized bis‐indole derived triazine‐bearing thiazolidinone derivatives were tested for in vitro α‐amylase, cancer cell and SARS‐COV‐2 enzymes under the positive control of Acarbose, Tetrandrine and GC‐376 as standard drugs. All derivatives showed varied range of biological activities against target enzymes having IC50 values ranging from 3.10±0.20 to 25.80±0.20 μM (α‐amylase), 0.20±0.30 to 19.10±0.20 μM (ant‐cancer) and 3.20±0.20 to 16.20±0.30 μM (SARS‐COV‐2), respectively. Specifically, derivatives 1, 3, 6, 8 and 9 were found to significantly active against target enzymes. Furthermore, the molecular docking approach was used to explore the binding interactions established by most active derivatives with the active sites of target enzymes and results corroborated that these active compounds developed several key interactions with the target enzymes and hence enhanced the enzymatic activities. Additionally, ADME prediction for the synthesized compounds were also explored which shows drug likeness of the synthesized compounds.