In silico DFT and molecular modeling of novel pyrazine-bearing thiazolidinone hybrids derivatives: elucidating in vitro anti-cancer and urease inhibitors.

In the present work, one of the leading health issues i.e. cancer was targeted by synthesizing and biologically investigating the potential of pyrazine-based thiazolidinone derivatives (1-13). The basic structure of the synthesized compounds was determined using a variety of spectroscopic techniques, including ¹H NMR, ¹³C NMR, and HREI-MS. These scaffolds were studied for their biological profiles as anti-cancer as well as anti-urease agents. The biological effectiveness of these compounds was compared using the reference tetrandrine (IC₅₀ = 4.50 ± 0.20 µM) and thiourea (IC₅₀ = 5.10 ± 0.10 µM), respectively. Among novel compounds, scaffold 3, 6, 7 and 10 demonstrated an excellent potency with highest inhibitory potential (IC₅₀ = 1.70 ± 0.10 and 1.30 ± 0.20 µM), (IC₅₀ = 4.20 ± 0.10 and 5.10 ± 0.30 µM), (IC₅₀ = 2.10 ± 0.10 and 3.20 ± 0.20 µM) and (IC₅₀ = 2.70 ± 0.20 and 4.20 ± 0.20 µM), respectively, out of which scaffold 3 emerged as the leading compound due to the presence of highly reactive -CF₃ moiety which interacts via hydrogen bonding. Molecular docking investigations of the potent compounds was also carried out which revealed the binding interactions of ligands with the active sites of enzyme. Moreover, the electronic properties, nucleophilic and electrophilic sited of the lead compounds were also studied under density functional theory (DFT).