Versatile anti-infective properties of pyrido- and dihydropyrido[2,3-d] pyrimidine-based compounds

A series of 1H-indeno[2 & PRIME;,1 & PRIME;:5,6]dihydropyrido[2,3-d]pyrimidine and 1H-indeno[2 & PRIME;,1 & PRIME;:5,6]pyrido[2,3-d]pyrimi-dine derivatives was prepared and screened for antiparasitic and viral RNase H inhibitory activity. Several compounds showed considerable activity against Toxoplasma gondii parasites and Leishmania major amastigotes, which warrants further investigation. Based on the structural similarities of certain derivatives with common viral RNase H inhibitors, a HIV-1 RNase H assay was used to study the RNase H inhibition by selected test compounds. Docking of active derivatives into the active site of the HIV-1 RNase H enzyme was carried out. The new compound 2a, inactive in the antiparasitic tests, showed distinct HIV-1 RNase H inhibition. Thus, ring substitution determines antiparasitic or HIV-1 RNase H inhibitory activity of this promising compound class.

Automated summary

A series of 1H-indeno[2',1'-5,6]dihydropyrido[2,3-d]pyrimidine and 1H-indeno[2',1'-5,6]pyrido[2,3-d]pyrimidine derivatives were synthesized and screened for their activity against parasites and viral RNase H. Some compounds exhibited significant activity against Toxoplasma gondii parasites and Leishmania major amastigotes, suggesting further investigation is warranted. A HIV-1 RNase H assay was used to study the RNase H inhibition of selected compounds, and docking simulations were performed to investigate their binding to the active site of the HIV-1 RNase H enzyme. Compound 2a, which was inactive against parasites, showed distinct HIV-1 RNase H inhibitory activity, suggesting that ring substitution determines the antiparasitic or HIV-1 RNase H inhibitory activity of this compound class.