Synthesis, characterization, and biological evaluation of the 2-hydroxy-benzylidene-cymanthrenyl-sulfonylhydrazone ligand and its complexes as inhibitors of 5-LOX and COX-2

In the search for new organometallic compounds that can be used as anti-inflammatory agents, the novel 2-hydroxy-benzylidene-cymanthrenyl-sulfonylhydrazone ligand [(eta Luo et al. (2022)5-C5H4S (O)2NH-N=CH-C6H4-2-OH)Mn(CO)3] (HL) and its palladium(II) (1a), nickel(II) (1b), and copper(II) (1c) complexes were synthesized. All compounds were characterized using conventional spectroscopic and analytical techniques (infrared and 1H and 13C NMR spectroscopy, mass spectrometry, and elemental analysis). The proposed molecular structures of HL, 1b, and 1c were confirmed via single-crystal X-ray diffraction. The inhibition of enzymes LOX and COX-2, which are associated with inflammation, by the new ligand and its metal complexes was studied. Our findings revealed that COX-2 was inhibited by the precursor [(eta Luo et al. (2022)5-C5H4S (O)2NH-NH2)Mn(CO)3] (p2) (23.6 mu M) and complex 1a (15.9 mu M), indicating high inhibitory potency. This study provides the first evidence of this type of complex functioning as a COX-2 inhibitor. Additionally, docking studies showed that the most significant interactions between COX-2 and the most potent inhibitors occurred through two key residues in the enzyme: Tyr385 and Tyr355.