Synthesis and Chemical Characterization of Chloroquine, Hydroxychloroquine, Zinc, and Cinnamic Acid Organocomplexes: Potential Drug Candidates for SARS‐CoV‐2 Treatment and Microbial Control

COVID‐19, caused by the SARS‐CoV‐2 virus, continues to be a significant concern due to its ongoing circulation and the risk of bacterial co‐infections, particularly with Staphylococcus aureus and Escherichia coli . Drug repositioning strategies utilizing compounds such as chloroquine and hydroxychloroquine, in conjunction with metal coordination techniques, have emerged as a promising therapeutic approach. The coordination of these drugs with bioactive metals, such as zinc(II), can enhance their selectivity and bioavailability while also reducing potential toxicity. These multifunctional metal–drug complexes are in line with current trends in medicinal inorganic chemistry, which focus on the development of broad‐spectrum agents with both antiviral and antibacterial properties. In the search for an efficient chemical compound to treat COVID‐19, two new metallodrugs were synthesized from chloroquine (CQ), complex 1 [Zn(cin) 2 (CQ) 4 ], and hydroxychloroquine (HCQ), complex 2 [Zn(cin) 2 (HCQ) 4 ], using drug repositioning and the bioisosterism strategy, which focuses on selective active compounds with low toxicity. Additionally, the IC 50 values in green monkey kidney cells ( Vero cells) were 16.6 and 8.8 µM after 72 h for complexes 1 and 2, respectively. Against E. coli bacteria, the complexes showed 16.02% and 14.11% CFU inhibition, compared to 24.83% inhibition by HCQ. Against S. aureus , the complexes showed 77.17% and 70.46% CFU inhibition, compared to 115.45% inhibition by HCQ. Furthermore, cytotoxicity and antiviral activity against COVID‐19 were tested, showing post‐infection cell viability of 82% for CQ, while the complexes showed 59% and 90%, respectively. In summary, zinc improved both the antiviral activity and the antibacterial activity against E. coli and S. aureus strains. Thus, we present two candidate drug compounds for new antiviral and antibacterial agents in the fight against SARS‐CoV‐2.