Mixed-ligand copper(ii)-diimine complexes of 3-formylchromone- N 4 -phenyl thiosemicarbazone: 5,6-dmp co-ligand confers enhanced cytotoxicity

• Published in: RSC advances 2024-10, Vol.14 (43), p.31704-31722
• Main Authors: Mamindla, Anjaneyulu, Murugan, Dhanashree, Varadhan, Manikandan, Ajaykamal, Tamilarasan, Rangasamy, Loganathan, Palaniandavar, Mallayan, Rajendiran, Venugopal
• Format: Article
• Language: English
• ISSN: 2046-2069; 2046-2069
• DOI: 10.1039/d4ra04997g

The promising biological applications of thiosemicarbazone derivatives have inspired the design, synthesis, and study of their Cu(ii) complexes for anticancer therapeutic applications. Herein, we have evaluated the DNA/protein binding, DNA cleaving, and cytotoxic properties of four mixed-ligand Cu(ii) complexes of the type [Cu(L)(diimine)](NO ) 1-4, where HL is 4-oxo-4 -chromene-3-carbaldehyde-4( )-phenylthiosemicarbazone and diimine is 2,2'-bipyridine (bpy, 1) 1,10-phenanthroline (phen, 2), 5,6-dimethyl-1,10-phenanthroline (5,6-dmp, 3), or dipyrido-[3,2- :2',3'- ]-quinoxaline (dpq, 4). Interestingly, complex 3 with higher lipophilicity shows stronger DNA binding and oxidative DNA cleavage, higher ROS production, and more reversible redox behaviour, resulting in its remarkable cytotoxicity (IC , 1.26 μM) against HeLa cervical cancer cells, and rendering it 5 times more potent than the widely used drug cisplatin. The same complex induces enhanced apoptotic cell death on HeLa cells but lower toxicity towards the non-cancerous PBMC cells. Molecular docking studies suggest that all the complexes bind in the minor groove of DNA and subdomain II of HSA, which is in close agreement with the experimental results. Also, 3 shows cytotoxicity higher than the analogous mixed ligand Cu(ii) complexes, reported already, emphasizing the importance of co-ligand in tuning the anticancer activity.