Comprehensive study for synthesis, antiviral activity, docking and ADME study for the new fluorinated hydrazonal and indeno[1,2-b]pyridine derivatives

Abstract

In this context, we synthesized a novel series of fluorinated-indeno[1,2-b]pyridin-5-one derivatives 6a-h and used spectral and elemental studies to demonstrate their structural validity. This series was achieved through the reaction of indandione with their related hydrazonal precursors 4a-h. The antiviral efficacy of sixteen derivatives, including fluorinated-indeno[1,2-b]pyridin-5-ones and their respective hydrazonal precursors, was assessed by a comprehensive screening procedure against a variety of viruses, including HSV-1, COX B3, and influenza A (H1N1). With respect to COX B3, five derivatives (4c, 4d, 4h, 6e, and 6h) had greater activity as shown by their reduced IC50 values, which ranged from 0.25 to 1268 nM. The presence of the 4‑bromo substituent in compound 4h was shown to be of significant importance in its activity against the three tested viruses; COX B3, H1N1, and HSV-1, as evidenced by the IC50 values of 0.78 µM, 5.54 µM, and 0.56 µM, respectively. Finally, ADME properties and molecular docking against Coxsackievirus B3 3C protease and RNA Polymerase of (4c, 4d, 4h, 6e, and 6h) were evaluated.