Metal complexes as potential modulators of inflammatory and autoimmune responses

Abstract

Over the past few decades, the realm of inorganic medicinal chemistry has been dominated by the study of the anti-cancer properties of transition metal complexes, particularly those based on platinum or ruthenium. However, comparatively less attention has been focused on the development of metal complexes for the treatment of inflammatory or autoimmune diseases. Metal complexes possess a number of advantages that render them as attractive alternatives to organic small molecules for the development of therapeutic agents. In this perspective, we highlight recent examples in the development of transition metal complexes as modulators of inflammatory and autoimmune responses. The studies presented here serve to highlight the potential of transition metal complexes in modulating inflammatory or immune pathways in cells.

Fig. 1. Chemical structures of cisplatin 1, NAMI-A 2 and KP-1019 3.

Fig. 2. Chemical structures of auranofin 4, solganal 5 and myochrysine 6.

Fig. 3. Chemical structure of aspirin 7 and crystal structure of Cu₂(asp)₄(DMSO)₂ 8.

Fig. 4. Chemical structure of the NSAID aceclofenac 9.

Fig. 5. Chemical structures of [Co(mef)₂(MeOH)₄] 10 and [Co(mef)₂(MeOH)₂(N^N)] 11a–c (where mef = mefenamic acid and N^N = 2,2′-bipyridine, 1,10-phenanthroline or (pyridine)₂) complexes.

Fig. 6. Chemical structures of the metal complexes 12–16 containing Schiff base ligands derived from anthranilic acid and aldoses.

Fig. 7. Chemical structures of the salicylaldehyde benzoyl hydrazones 17 and 18.

Fig. 8. Chemical structures of the transition metal complexes 19–21 bearing Schiff base ligands derived from salicylaldehyde and glycine.

Fig. 9. Chemical structures of the Co(ii), Ni(ii), Cu(ii) and Zn(ii) complexes 22–29 with Schiff bases derived from 2-mercapto-3-formyl quinoline or 2-hydroxy-3-formyl quinoline with 2,6-diaminopyridine (DAP).

Fig. 10. Chemical structure of BIPTZ 30.

Fig. 11. Chemical structures of the chromium-containing arene (arene–Cr(CO)₃) complexes 31a–d.

Fig. 12. Chemical structures of the transition metal complexes 32–35 of pyridine-2-ethyl-(3-carboxylideneamine)-3-(2-phenyl)-1,2-dihydroquinazolin-4(3H)-one.

Fig. 13. Chemical structures of the complexes of enoxacin (eno) 36, [M(eno)₂(OH₂)₂]·3OH₂ 37–39 (where M = Cu(ii), Ni(ii) or Mn(ii)) and [Fe(eno)(OH₂)₂]Cl·4OH₂ 40.

Fig. 14. Chemical structure of fac-[Re(phendione)(CO)₃Cl] 41 (where phendione = 1,10-phenanthroline-5,6-dione).

Fig. 15. Synthesis and chemical structures of the gold(i) complexes with the general formula [Au(L)(PPh₃)]·xOH₂ (42a–h; x = 0–1.5).

Fig. 16. Chemical structures of CPA-1 43, CPA-3 44, CPA-7 45 and Pt(iv)Cl₄ 46 and IS3 295 47.

Fig. 17. Chemical structure of the cyclometalated Ir(iii) complex [Ir(ppy)₂(biq)]PF₆ 48.

Fig. 18. Chemical of structure of Rh(iii) complex 49.

Fig. 19. Chemical structures of rac-[Rh(ppy)₂(CNL)₂]OTf 50 and rac-[Rh(bzq)₂(CNL)₂]OTf 51 (ppy = 2-phenylpyridine; bzq = benzoquinoline and CNL = 2-naphthylisocyanide).

Fig. 20. Chemical of structure of Rh(iii) complex 52.

Fig. 21. Chemical structures of the coordination complexes 53, 54 and 55 as functional proteomimetics of the Src homology 2 (SH2) phosphopeptide-binding domain.

Fig. 22. Chemical structure of Rh(iii) complex 56.

Fig. 23. The dismutation of O₂˙^– catalyzed by MnSOD.

Fig. 24. Chemical structures of Mn porphyrins, Mn cyclic polyamines and Mn salen derivatives.

Chung-Hang Leung

Sheng Lin

Hai-Jing Zhong

Dik-Lung Ma