Multi-component sustainable catalytic crafting of novel heterocyclic spiranes as topoisomerase II inhibitors

Abstract

Scientists have recently focused on crafting a more natural approach to catalysis to make organic synthesis more sustainable and eco-friendly. This manuscript highlights an environment-friendly, efficient synthesis of novel spirocyclic derivatives (QP 1 – QP 12) of quinoxaline pyrimidine mediated through sustainable green catalyst potash alum. The research was conducted with thoroughness, as computational techniques were used to examine the interaction of topoisomerase II enzyme with spiro compounds. The computational analysis was also accompanied to determine the interaction of spirocyclic compounds with biomolecules, i.e., 1BNA and BSA. Anticancer activity was carried out on MCF-7 regarding IC₅₀ value, which ranges between 76.67 and 138.34 µg/mL. The spirocyclic compounds showed good antimicrobial activity and cytotoxic nature against five bacterial strains and artemia cysts. The compound’s MIC and LC₅₀ values were found in the 135–195 µM range and 6.26–10.91 µg/mL, respectively. Spectroscopic techniques were performed for evaluating the binding strength between spirocyclic compounds and biomolecules. The binding constant values of QP 1 – QP 12 with CT-DNA and BSA were found in the range of 0.61–1.45 × 10⁵ M⁻¹ and 0.16–2.19 × 10⁴ M⁻¹, respectively. SwissADME and admetSAR, two online platforms, were used to assess the pharmacokinetic profile and determine the drug-likeness of the synthesized compounds.