Novel Xylenyl-Spaced Bis-Thiazoles/Thiazines: Synthesis, Biological Profile as Herpes Simplex Virus Type 1 Inhibitors and in Silico Simulations

Aims: Development of some potent bis-thiazole and bis-thiazine derivatives that could be used as antiviral prototypes. Materials & methods: Xylenyl-spaced bis-carbazone scaffold 3 was used as a versatile building block for bis-thiazole derivatives 6a–e and 9a–d and bis-thiazine derivatives 12a–f. These bis-heterocycles were screened as herpes simplex virus type 1 (HSV-1) inhibitors. Results: The new bis-heterocyclic compounds showed remarkable antiviral activity (e.g., compound 6d cytotoxicity concentration CC50 >500 μg/ml). The antiviral capacity of the synthesized bis-compounds was supported by a molecular docking study against the glycoprotein D receptor of HSV-1. Compounds 6b, 9b, and 12c displayed the best binding coefficients. Conclusion: A new series of xylenyl-spaced bis-carbazone scaffolds were used as a building scaffold to construct a host of bis-thiazole/thiazine derivatives that could be used as antiviral prototypes.