Synthesis and biological evaluation of primaquine– chloroquine twin drug: a novel heme-interacting molecule prevents free heme and hydroxyl radical-mediated protein degradation

摘要

Accumulations of oxidized and degraded proteins are the markers for oxidative stress. Degradation of hemoprotein e.g. hemoglobin during different pathological conditions produces heme, which induces oxidative stress and inflammation through its pro-oxidant nature and leads to protein degradation. Moreover reduced transition-metal ions Fe~(2+) can generate toxic hydroxyl radicals (OH) and leads to protein degradation. Therefore, synthesis of a compound that will detoxify free heme, chelate Fe~(+2) and show antioxidant activity by scavenging _OH would be beneficial against protein degradation. Here, we report the synthesis of a novel heme-interacting primaquine–chloroquine twin drug (PQCL) that could chelate free iron and showed excellent antioxidant activity as evident from ferric reducing antioxidant power. PQCL prevented OH and heme-mediated protein degradation. PQCL also could scavenge nitrogen-centered free radical (2,2-diphenyl-1-picrylhydrazyl). Thus, we have synthesized PQCL, a hemeinteracting molecule, which is capable to prevent free heme and _OH-mediated protein degradation.