Synthesis, DFT calculations, In silico studies, and biological evaluation of pyrano[2,3-c]pyrazole and pyrazolo[4′,3′:5,6]pyrano[2,3-d]pyrimidine derivatives

Abstract

An eco-friendly approach was conducted for synthesizing pyrano[2,3-c]pyrazoles M1-M25 via a one-pot reaction of hydrazine hydrate 99%, ethyl acetoacetate or diethyl malonate, carbonyl group source, and active methylene compounds. Besides, pyrazolo[4′,3′:5,6]pyrano[2,3-d]pyrimidines M26-M31 was synthesized via intramolecular cyclization of M10 and M13. Thereafter, the antimicrobial, antioxidant, and anti-cancer activities of the titled compounds were evaluated utilizing an array of techniques. Fortunately, the vast majority of the compounds exhibited promising biological activities. Over and above, in silico study was employed to determine the expected mode of action of the synthesized compounds. M21 was the most promising anti-bacterial agent, while M5 was the most cytotoxic compound. Finally, DFT theoretical calculations were used to study the stability and structural parameters of the newly synthesized compounds. DFT calculations showed the energy gaps between the HOMO-LUMO with all the investigated compounds in a range of 4.04–5.66 eV allowing for easy exchange of electrons and the reactivity.