Synthesis, Characterization and Evaluation of the Antibacterial and Antitumor Activity of HalogenatedSalen Copper (II) Complexes derived from Camphoric Acid

Abstract

Platinum metal complexes are the most common chemotherapeutics currently used in cancer treatment. However, the frequent adverse effects, as well as acquired resistance by tumor cells, urge the development of effective alternatives. In the recent past, copper complexes with Schiff base ligands have emerged as good alternatives, showing interesting results. Accordingly, and in continuation of previous studies in this area, three new camphoric acid‐derived halogenated salen ligands and their corresponding Cu (II) complexes were synthesized and their antitumor activity was evaluated in order to determine the influence of the type and number of halogens present (Br, Cl). The in vitro cytotoxic activity was screened against colorectal WiDr and LS1034 and against breast MCF‐7 and HCC1806 cancer cell lines. The results proved the halogenated complexes to be very efficient, the tetrachlorinated Cu (II) complex being the most promising, presenting IC50 of 0.63–1.09 μM for the cell lines studied. The complex also shows selectivity to colorectal cancer cells compared to non‐tumor colon cells. It is worth highlighting that the tetrachlorinated Cu (II) complex, our most efficient complex, shows a significantly more powerful antitumor effect than the reference drugs currently used in conventional chemotherapy. The halogenated salen and corresponding complexes were also screened for their antimicrobial activity against four bacterial species‐Staphylococcus aureus, Enterococcus faecalis, Escherichia coli and Pseudomonas aeruginosa‐and four fungal species‐Candida albicans, Candida glabrata, Aspergillus fumigatus and Alternaria alternata. The compounds were found to exhibit moderate to strong antibacterial activity against the bacterial strains studied. NMR studies and theoretical calculations provided some insight into the structure of the ligands and copper complexes. Considering the results presented herein, our work validates the potential use of copper‐based chemotherapeutics as alternatives for cancer treatment.

RETRACTED: Taguchi-Assisted Optimization Technique and Density Functional Theory for Green Synthesis of a Novel Cu-MOF Derived From Caffeic Acid and Its Anticancerious Activities

“…It is worth noting that the true nature of the active sites in many MOFs, including metal ions, is saturated with the coordination of organic ligands (Zou et al, 2007). Copper has more antibacterial and anticancer properties than others (Gu et al, 2017;Pires et al, 2020). The bactericidal mechanism of Cu-MOF is due to the diffusion of Cu 2+ ions.…”

Synthesis, spectroscopic, electrochemical characterization, density functional theory (DFT), time dependent density functional theory (TD‐DFT), and antibacterial studies of some Co(II), Ni(II), and Cu(II) chelates of (E)‐4‐(1,5‐dimethyl‐3‐oxo‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐4‐yl)‐1‐(3‐hydroxynaphthalen‐2‐yl)methylene) thiosemicarbazide Schiff base ligand

“…Furthermore, the free ligand and its metal chelates were more active against Gram‐positive bacteria ( S. aureus ) compared to Gram‐negative bacteria ( E. coli ). [ 95 ] In Gram‐positive bacteria, chelates 4 , 5 , and 6 were highly active with comparable zones of inhibition of 14.3, 14.8, and 14.6 mm, which is almost two times better than the ligand. However, in Gram‐negative bacteria metal chelate 5 was the most active, screening a comparable zone of inhibition of 16.1 mm, displaying better efficiency than the ligand and the other chelates.…”

Synthesis and Cytotoxicity Studies of Br‐Substituted Salphen Organic Compounds

“…[41][42][43] In these cases, as in other anticancer drugs, the compounds act under different mechanisms that depend not only upon their molecular descriptors but also upon other multifactorial phenomena that may either converge or not: e. g., metabolic pathway alterations, enzymatic inhibition, nucleic acid intercalation, unnatural allosterism, membrane disruption, etc. In this regard, the effect of introducing bromine groups in Schiff bases to enhance their antiproliferative properties was very recently confirmed in Salen [44][45][46] and Salphen-like [47] metal complexes from mostly Cu(II) and some examples from Fe(III) or Mn(III). In these works, the authors reported that bromine atoms symmetrically incorporated to each of the two o-salicylaldehyde moieties of a single skeleton could render between 12 % and 6-fold lower IC50 values if compared to their non-halogenated complex counterparts, thus facilitating the access to competitive values below 29 μM in different cancer cell lines.…”