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 mu g/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.

Automated summary

A new series of xylenyl-spaced bis-carbazones were successfully synthesized and used as building blocks to construct a variety of bis-thiazole/thiazine derivatives. These newly synthesized compounds exhibited remarkable antiviral activity, especially compound 6d. Molecular docking study further confirmed the antiviral mechanism of these compounds.