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

[Display omitted] •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 prepared.•High activity against Toxoplasma gondii parasites and Leishmania major amastigotes was observed.•A catechol derivative inhibits HIV-1 RT-associated RNase H.•Docking and ADME-T calculations confirmed drug-like properties of active compounds. 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 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.