Synthesis and anticancer mechanisms of zinc(ii)-8-hydroxyquinoline complexes with 1,10-phenanthroline ancillary ligands?

Dalton Transactions Pub Date: 2023-03-10 DOI: 10.1039/D3DT00150D

Abstract

Twenty new zinc(II) complexes with 8-hydroxyquinoline (H-Q1–H-Q6) in the presence of 1,10-phenanthroline derivatives (D1–D10) were synthesized and formulated as [Zn(Q1)2(D1)] (DQ1), [Zn(Q2)2(D2)]·CH3OH (DQ2), [Zn(Q1)2(D3)] (DQ3), [Zn(Q1)2(D4)] (DQ4), [Zn(Q3)2(D5)] (DQ5), [Zn(Q3)2(D4)] (DQ6), [Zn(Q4)2(D5)]·CH3OH (DQ7), [Zn(Q4)2(D6)] (DQ8), [Zn(Q4)2(D3)]·CH3OH (DQ9), [Zn(Q4)2(D1)]·H2O (DQ10), [Zn(Q5)2(D4)] (DQ11), [Zn(Q6)2(D6)]·CH3OH (DQ12), [Zn(Q5)2(D2)]·5CH3OH·H2O (DQ13), [Zn(Q5)2(D7)]·CH3OH (DQ14), [Zn(Q5)2(D8)]·CH2Cl2 (DQ15), [Zn(Q5)2(D9)] (DQ16), [Zn(Q5)2(D1)] (DQ17), [Zn(Q5)2(D5)] (DQ18), [Zn(Q5)2(D10)]·CH2Cl2 (DQ19) and [Zn(Q5)2(D3)] (DQ20). They were characterized using multiple techniques. The cytotoxicity of DQ1–DQ20 was screened using human cisplatin-resistant SK-OV-3/DDP ovarian cancer (SK-OV-3CR) cells and normal hepatocyte (HL-7702) cells. Complex DQ6 showed low IC50 values (2.25 ± 0.13 μM) on SK-OV-3CR cells, more than 3.0–8.0 times more cytotoxic than DQ1–DQ5 and DQ7–DQ20 (≥6.78 μM), and even 22.2 times more cytotoxic than the standard cisplatin, the corresponding free H-Q1–H-Q6 and D1–D10 alone (>50 μM). As a comparison, DQ1–DQ20 displayed nontoxic rates against healthy HL-7702 cells. Furthermore, DQ6 and DQ11 induced significant apoptosis via mitophagy pathways. DQ6 also significantly inhibited tumor growth in an in vivo SK-OV-3-xenograft model (ca. 49.7%). Thus, DQ6 may serve as a lead complex for the discovery of new antitumor agents.

Graphical abstract: Synthesis and anticancer mechanisms of zinc(ii)-8-hydroxyquinoline complexes with 1,10-phenanthroline ancillary ligands
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