Metal Complexes with Schiff Bases: Data Collection and Recent Studies on Biological Activities

Metal complexes play a crucial role in pharmaceutical sciences owing to their wide and significant activities. Schiff bases (SBs) are multifaceted pharmacophores capable of forming chelating complexes with various metals in different oxidation states. Complexes with SBs are extensively studied for their numerous advantages, including low cost and simple synthetic strategies. They have been reported to possess a variety of biological activities, including antimicrobial, anticancer, antioxidant, antimalarial, analgesic, antiviral, antipyretic, and antidiabetic ones. This review summarizes the most recent studies on the antimicrobial and antiproliferative activities of SBs-metal complexes. Moreover, recent studies regarding mononuclear and binuclear complexes with SBs are described, including antioxidant, antidiabetic, antimalarial, antileishmanial, anti-Alzheimer, and catecholase activities.


Introduction
Coordination chemistry is an attractive discipline for chemists and researchers who have reached pharmaco-therapeutic success in the field of remediation of severe diseases and improvements of several drugs. SBs are versatile organic compounds deriving from the condensation of primary amines with carbonyl compounds; they contain an imine group (azomethine, >C=N-). In addition to their usefulness in catalysis [1], they showed diverse biological activities [2,3] including antimicrobial [4], antiproliferative [5], antimalarial [6,7], analgesic, anxiolytic [8], antidepressant [9], anti-inflammatory [10,11], antiviral [12], antipyretic, antibacterial [13] and antifungal [14]. Moreover, several studies on SBs-metal complexes showed their use as anti-Alzheimer agents [15][16][17], and their potential in the management of diabetes mellitus [18]. Some SBs derivatives have demonstrated α-glucosidase inhibition and antiglycation activity [19,20], whereas other derivatives were synthesized and used as fluorescent sensors for the diabetic biomarker betahydroxybutyrate (β-HB) [21]. Metal complexes of different metals with SBs have demonstrated a myriad of activities [22,23], and catalytic applications [24] in which metals are represented by Mo [25], Cu [26][27][28], Zr [29][30][31], Pd [32], Cu [33], Ni [34], Ru [35], Mn [36], Zn [37,38] and W [39]. Several studies have been carried out on the transmetalation of by Mo [25], Cu [26][27][28], Zr [29][30][31], Pd [32], Cu [33], Ni [34], Ru [35], Mn [36], Zn [37,38] and W [39]. Several studies have been carried out on the transmetalation of Zn-SB complexes with other metal ions [40] for various purposes, such as the detection of Cu 2+ ions in aqueous solution [41] and the inhibition of acid-induced steel corrosion [42]. Recent studies addressed luminescence and fluorescence taking advantage of lanthanide (Ln 3+ ) complexes with SBs [43]. It is noteworthy that not only mononuclear but also binuclear metal complexes with SBs have recently attracted attention in diverse fields of research ( Figure 1). Chi et al. [44] have studied a Zn-Yb binuclear SBs complex, which enhanced near-infrared (NIR) luminescence. A ytterbium SBs complex was suggested for NIR-emitting organic light emitting diode (OLED), a technology recently emerged for its use in a vast range of applications such as medical diagnostics (oximetry, drug delivery, tumor therapy, atherosclerosis treatment) [45]. Fluorescence properties were found for mononuclear Dy(III)/heteropolynuclear Zn(II)-Dy (III) SBs [46]. Nano SBs are considered the most multitasking ligands as they are able to form complexes with metals [47]. SBs-metal complexes are frequently used as environmentally friendly catalysts [48]: Ni-SBs complexes have been used for green catalysis [49], whereas a copper (II) SBs complex was fixed on the surface of iron oxide nanoparticles, which was used for oxidation of olefins with H2O2 as an eco-friendly oxidant [50]. Despite the importance of all these activities, we would like to focus on the biological aspects of SBs-metal complexes. Indeed, various biological activities have been widely described for SBs-metal complexes, including antimicrobial [51,52], antioxidant, anticancer [53], and some DNA interaction studies [54][55][56]. The antiproliferative activity of SBs-metal complexes has been recently reviewed [57,58]. In this review, the most recent studies on these complexes are summarized, mainly focusing on the antimicrobial activity, which is one of the main challenges, currently, to overcome antimicrobial resistance [59]. For binuclear complexes, most of the studies are also in relation to antiproliferative, antioxidant, and catecholase activities.

Mononuclear SBs Complexes with Antibacterial and Antiproliferative Activities
The antimicrobial and antiproliferative activities of some mononuclear SBs complexes are reported in Table 1. Generally, the data refer to the lowest concentration of the assayed antimicrobial agent (minimal inhibitory concentration, MIC) that, under defined test conditions, inhibits the visible growth of the bacterium being investigated. Microbes were generally referred to in either the American Type Culture Collection (ATCC), Persian Type Culture Collection (PTCC), or Agricultural Culture Collection of China (ACCC),

Mononuclear SBs Complexes with Antibacterial and Antiproliferative Activities
The antimicrobial and antiproliferative activities of some mononuclear SBs complexes are reported in Table 1. Generally, the data refer to the lowest concentration of the assayed antimicrobial agent (minimal inhibitory concentration, MIC) that, under defined test conditions, inhibits the visible growth of the bacterium being investigated. Microbes were generally referred to in either the American Type Culture Collection (ATCC), Persian Type Culture Collection (PTCC), or Agricultural Culture Collection of China (ACCC), unless otherwise detailed. Several authors determined the antimicrobial activity by measuring the diameter (as mm) of the zone showing the complete inhibition (inhibition zone diameter, IZD). In one or more cases, the bacterial suspensions were prepared via the direct colony method. At the end of the assay, the number of survived bacterial colonies (measured as CFUs) was quantified and the rates of colony-forming units (R) were calculated as a percentage with respect to the control, which contained no antibacterial agent. Cytotoxicity studies were reported giving IC 50 values (the concentration that kills or inhibits the cell viability by 50%). Rajakkani et al., (2021) [60] reported the synthesis and biological evaluation of stable mononuclear metal (II) complexes (specifically, Co, Ni, and Zn) with an unsymmetrical 13-membered Knoevenagel macrocyclic SB ligand. Antimicrobial activity was determined by using the well dilution method against bacteria (two Gram-positive, Staphylococcus aureus, Bacillus subtilis, and three Gram-negative, Escherichia coli, Klebsiella pneumoniae, Salmonella typhi) compared with the standard kanamycin (MIC = 1.4, 1.2, 1.8, 2.2 and 2.0 µM, respectively) and fungi (Aspergillus niger, Fusarium solani, Aspergillus flavus, Rhizoctonia bataticola, Candida albicans) compared with the standard fluconazole (MIC = 1.2, 1.5, 1.2, 1.8 and 1.8 µM, respectively). The interesting results of the complex [CuL]Cl 2 (1), higher than those obtained with the ligand, were justified by the chelation theory, in which the chelation decreases the polarity of the metal ion partially sharing its positive charge with donor groups of ligand and the potential π electron delocalization may be found around each ring. Moreover, antiproliferative assays were carried out against human breast (MCF-7), cervical (HeLa), and epithelioma (Hep-2) cancer cell lines, as well as against the normal human dermal fibroblast (NHDF) cell line, by the MTT assay method. Indeed, higher anticancer activity of Cu(II) complex was interesting as compared to cisplatin (IC 50 = 15 ± 1.2, 18 ± 1.2, 14 ± 1.0 µM, and 82 ± 1.0 µM, respectively).
Al-Shboul et al., (2022) [64] reported an interesting study on metal complexes (Fe, Cu, and Zn) of substituted salicylideneamino-4,4 -dimethyl-1,1 -biphenyl SBs, which show differences of activities depending on the coordinating metal. Complexes with zinc, Z2Zn (7), Z3Zn (8), and Z4Zn (9), showed antimicrobial activity against Gram-positive bacteria (M. luteus ATCC 934 and S. aureus 29213), compared with amoxicillin (IZD = 25 mm and 35 mm, respectively) whereas complexes with copper, Z1Cu (10) and Z3Cu (11), showed activity against the Gram-negative E. coli ATCC25922 (IZD = 10 mm for amoxicillin). All complexes were also tested for their antiproliferative activities against parental breast cancer (MCF7) [65], non-small-cell lung cancer (A549), and human dermal fibroblast (HDF) cell lines, compared to doxorubicin (0.03 µg/mL, 0.15 µg/mL and 0.37 µg/mL, respectively) via the MTT assay. The highest antiproliferative activity was found for the copper complex Z2Cu (12). Maia et al., (2022) [66] recently described the synthesis of a nickel(II) chloride SB complex [(Ni(L2), 13] and its antimicrobial activity evaluation against multi-resistant S. aureus 10 (from catheter tip), E. coli 06 (from urine culture) and P. aeruginosa 15 (from rectal swab) strains and leishmania. This complex showed inhibition of the bacterial growth for the strains of P. aeruginosa, at the concentration of 256 µg/mL, while it was not active against E. coli and S. aureus (MIC ≥ 1024 µg/mL). The modulation of the antibiotic activity against multi-resistant strains was also studied, indeed complex 13 increased the activity of gentamicin against S. aureus, decreasing the MIC from 50.8 to 16 µg/mL that, proportionally, corresponds to a 68.5% reduction in the amount of gentamicin needed to produce the same effect on the strain under study. For E. coli, the decrease was about 20.6% (MIC from 32 to 25.4 µg/mL). Moreover, complex 13 increased the activity of amikacin against E. coli with a 37% reduction (MIC from 203.2 to 128 µg/mL). Thus, the same complex in combination with gentamicin or amikacin determined a decrease in the antimicrobial activity in both cases. The compound also showed interesting results against Leishmania amazonensis promastigote via the Promastigotes assay, by measuring the culture density after 24, 48, and 72 h of incubation and counting the viable parasites in a Neubauer chamber, in order to determine the IC 50 .
An interesting article has been recently reported by Hassona et al. [73] regarding the anticancer activity of a Pd complex with an SB the palladium(II) 2-hydroxyimino-3-(2hydrazonopyridyl)-butane [PdLCl]·H 2 O (19). This study investigated the antitumor and apoptotic activities of the complex against Ehrlich carcinoma in vitro and in vivo. Ehrlich ascites carcinoma (EAC) cells were used, and caspase 8 activity was estimated using the Caspase 8 FAM-FLICA kit. In vitro, the complex reduced the EAC cells' viability, enhanced the caspase 8 activity, arrested the cell cycle at G0/G1, and reduced the G2(M) population, indicating that the antiproliferative and antitumor activities were likely due to the induction of apoptosis. In vivo studies were carried out on adult female Swiss albino mice, divided into different groups: normal, EAC, EAC+cisplatin, EAC+complex, and normal+complex. Treatment with the complex in a dose-dependent mode significantly diminished the tumor volume and weight, prolonged the median survival time (MST) and the percent increase in life span (ILS%), enhanced the mice body weight gain, and improved the blood indexes. Treatment of EAC-bearing mice with the complex highest dose showed more desirable outcomes than the treatment with cisplatin, moreover, the normal+complex group showed no pathological changes, indicating safety. Zn(II)] complexes for their antimicrobial and anti-inflammatory activity. The antimicrobial activity was assessed against bacteria (B. subtilis, S. aureus, E. coli, K. pneumoniae, and P. aeruginosa) and fungi (C. albicans and A. niger) by the agar well diffusion method. The Zn complex Zn(HMHC)2]H2O (16) showed high activity against the bacteria K. pneumoniae and B. subtilis with respect to the standard amikacin (IZD = 24 and 22 mm, respectively) and against fungi compared to nystatin (C. albicans and A. niger, IZD = 15 and 17 mm, respectively). The enhanced activity of the complexes was explained on the basis of the Overtone's concept [69] and Tweedy's Chelation theory [70]. Moreover, the anti-inflammatory activity of complexes was studied by using the inhibition of albumin denaturation technique, according to a partially modified literature procedure [71]. Complex 16 showed activity in inhibiting the heat-induced albumin denaturation at different concentrations, showing a maximum inhibition of 92.2% at a concentration of 100 μg/mL, compared to diclofenac sodium (100% inhibition). Gowdhami et al. (2022) [72] recently described the antiproliferative activity of cobalt(III) SB complexes (17 = Co(1-phenylbutane-1,3-dione)(heptylamine)2](-ClO4) and 18 = [Co(1-phenylbutane-1,3-dione)(dodecyl amine)2](-ClO4)] against human breast MCF-7 and lung A549 cancer cell using the MTT cell viability assay. The two complexes showed high antiproliferative activity compared to the standard cisplatin (IC50 = 11.6 ± 0.1 µM and 14.4 ± 0.1 µM, respectively).
An interesting article has been recently reported by Hassona et al. [73] regarding the anticancer activity of a Pd complex with an SB the palladium(II) 2-hydroxyimino-3-(2hydrazonopyridyl)-butane [PdLCl] . H2O (19). This study investigated the antitumor and apoptotic activities of the complex against Ehrlich carcinoma in vitro and in vivo. Ehrlich ascites carcinoma (EAC) cells were used, and caspase 8 activity was estimated using the Caspase 8 FAM-FLICA kit. In vitro, the complex reduced the EAC cells' viability, enhanced the caspase 8 activity, arrested the cell cycle at G0/G1, and reduced the G2(M) population, indicating that the antiproliferative and antitumor activities were likely due to the induction of apoptosis. In vivo studies were carried out on adult female Swiss albino mice, divided into different groups: normal, EAC, EAC+cisplatin, EAC+complex, and nor-mal+complex. Treatment with the complex in a dose-dependent mode significantly diminished the tumor volume and weight, prolonged the median survival time (MST) and the percent increase in life span (ILS%), enhanced the mice body weight gain, and improved the blood indexes. Treatment of EAC-bearing mice with the complex highest dose showed more desirable outcomes than the treatment with cisplatin, moreover, the nor-mal+complex group showed no pathological changes, indicating safety.             (21), with a 65.54% inhibition value that is close to the value of the standard chloroquine diphosphate 68.90%. The results were surprising for the antidiabetic activity, which was tested by the α-amylase inhibition assay. In this assay, all the complexes exhibited values of inhibition in the range of 53.03-55.55%, whereas the SB ligand was more active (59.09%), and the standard acarbose showed 80.80% inhibition. Moreover, antioxidant studies were carried out via DPPH assay, indicating that the Fe(III) complex 21 scavenged the DPPH radicals close to acarbose (97.79%).
Şenocak et al., (2021) [76] studied three SBs Zn(II) complexes with amino acids for their potential activities in diabetes and Alzheimer disease. The activity for Alzheimer disease was evaluated in comparison with the standard tacrine, by measuring the activity on the AChE (IC50 = 25.72 µM and Ki = 23.11 ± 4.05 µM) and BChE (IC50 = 18.06 µM and Ki = 14.10 ± 5.62 µM). The three complexes effectively inhibited the AChE, being more active than the standard; the major activity was found for complexes 22 and 23. Moreover, the inhibitory effect of the three complexes on the α-glycosidase activity was determined using the p-nitrophenyl-D-glycopyranoside substrate, according to a previously reported procedure [77]. The three complexes showed inhibitory effects similar to the standard αglycosidase inhibitor acarbose (IC50 = 49.61 µM and Ki = 55.84 ± 7.35 µM), being complex 24 the most active.
Deswal et al., (2022) [78] recently reported a study on transition metal complexes, namely cobalt (II), nickel(II), copper(II), and zinc(II), with SB ligands and their potential antidiabetic activity by in vitro experiments on α-amylase and α-glucosidase enzymes. Complexes 25 and 26 showed good activities with IC50 values close to those of the standard acarbose (IC50 = 1.28 ± 0.05 and 0.58 ± 0.06 μmol/mL, respectively). This outcome was supported by molecular docking studies carried out using the active site of the human  (21), with a 65.54% inhibition value that is close to the value of the standard chloroquine diphosphate 68.90%. The results were surprising for the antidiabetic activity, which was tested by the α-amylase inhibition assay. In this assay, all the complexes exhibited values of inhibition in the range of 53.03-55.55%, whereas the SB ligand was more active (59.09%), and the standard acarbose showed 80.80% inhibition. Moreover, antioxidant studies were carried out via DPPH assay, indicating that the Fe(III) complex 21 scavenged the DPPH radicals close to acarbose (97.79%).
Senocak et al., (2021) [76] studied three SBs Zn(II) complexes with amino acids for their potential activities in diabetes and Alzheimer disease. The activity for Alzheimer disease was evaluated in comparison with the standard tacrine, by measuring the activity on the AChE (IC 50 = 25.72 µM and K i = 23.11 ± 4.05 µM) and BChE (IC 50 = 18.06 µM and K i = 14.10 ± 5.62 µM). The three complexes effectively inhibited the AChE, being more active than the standard; the major activity was found for complexes 22 and 23. Moreover, the inhibitory effect of the three complexes on the α-glycosidase activity was determined using the p-nitrophenyl-D-glycopyranoside substrate, according to a previously reported procedure [77]. The three complexes showed inhibitory effects similar to the standard αglycosidase inhibitor acarbose (IC 50 = 49.61 µM and K i = 55.84 ± 7.35 µM), being complex 24 the most active.
Deswal et al., (2022) [78] recently reported a study on transition metal complexes, namely cobalt (II), nickel(II), copper(II), and zinc(II), with SB ligands and their potential antidiabetic activity by in vitro experiments on α-amylase and α-glucosidase enzymes. Complexes 25 and 26 showed good activities with IC 50 values close to those of the standard acarbose (IC 50 = 1.28 ± 0.05 and 0.58 ± 0.06 µmol/mL, respectively). This outcome was supported by molecular docking studies carried out using the active site of the human pancreatic α-amylase (PDB code: 1BSI) and α-glucosidase (PDB code: 5ZCC). Moreover, in silico studies to check the drug-likeness were carried out, showing that the complexes can be used as orally active drugs. Table 2 summarizes the reported recent studies.

Binuclear SBs Complexes
Binuclear complexes may present in the same or two different metals and are often more interesting than the mononuclear variants in chemical and biological studies. Binuclear complexes with SBs have been widely studied as catalysts [79][80][81], in fluorescence and luminescence studies [82,83], and also antimicrobial activities were reported [84,85]. More recently, binuclear complexes with SBs have been suggested for the therapy of COVID-19 disease [86] on the basis of molecular modeling studies [87].
Dicopper(II) complexes are often used to study catecholase (or catechol oxidase) activity, a type-3 copper protein with a dicopper(II) moiety. Catecholase can reversibly bind oxygen at room temperature, thus it can be used to oxidize phenols to the respective obenzoquinones. Specifically, dicopper(II) complexes are often used to explore the catalytic activity of catecholase oxidation [88]. Recent studies on binuclear complexes with SBs are summarized in Table 3.

Binuclear SBs Complexes
Binuclear complexes may present in the same or two different metals and are often more interesting than the mononuclear variants in chemical and biological studies. Binuclear complexes with SBs have been widely studied as catalysts [79][80][81], in fluorescence and luminescence studies [82,83], and also antimicrobial activities were reported [84,85]. More recently, binuclear complexes with SBs have been suggested for the therapy of COVID-19 disease [86] on the basis of molecular modeling studies [87].
Dicopper(II) complexes are often used to study catecholase (or catechol oxidase) activity, a type-3 copper protein with a dicopper(II) moiety. Catecholase can reversibly bind oxygen at room temperature, thus it can be used to oxidize phenols to the respective obenzoquinones. Specifically, dicopper(II) complexes are often used to explore the catalytic activity of catecholase oxidation [88]. Recent studies on binuclear complexes with SBs are summarized in Table 3. Table 3. Binuclear metal complexes with SBs.

Structure Compound
Antimicrobial and Antioxidant Activities

Binuclear SBs Complexes
Binuclear complexes may present in the same or two different metals and are often more interesting than the mononuclear variants in chemical and biological studies. Binuclear complexes with SBs have been widely studied as catalysts [79][80][81], in fluorescence and luminescence studies [82,83], and also antimicrobial activities were reported [84,85]. More recently, binuclear complexes with SBs have been suggested for the therapy of COVID-19 disease [86] on the basis of molecular modeling studies [87].
Dicopper(II) complexes are often used to study catecholase (or catechol oxidase) activity, a type-3 copper protein with a dicopper(II) moiety. Catecholase can reversibly bind oxygen at room temperature, thus it can be used to oxidize phenols to the respective o-benzoquinones. Specifically, dicopper(II) complexes are often used to explore the catalytic activity of catecholase oxidation [88]. Recent studies on binuclear complexes with SBs are summarized in Table 3.

Binuclear SBs Complexes
Binuclear complexes may present in the same or two different metals and are often more interesting than the mononuclear variants in chemical and biological studies. Binuclear complexes with SBs have been widely studied as catalysts [79][80][81], in fluorescence and luminescence studies [82,83], and also antimicrobial activities were reported [84,85]. More recently, binuclear complexes with SBs have been suggested for the therapy of COVID-19 disease [86] on the basis of molecular modeling studies [87].
Dicopper(II) complexes are often used to study catecholase (or catechol oxidase) activity, a type-3 copper protein with a dicopper(II) moiety. Catecholase can reversibly bind oxygen at room temperature, thus it can be used to oxidize phenols to the respective obenzoquinones. Specifically, dicopper(II) complexes are often used to explore the catalytic activity of catecholase oxidation [88]. Recent studies on binuclear complexes with SBs are summarized in Table 3.

Binuclear SBs Complexes
Binuclear complexes may present in the same or two different metals and are often more interesting than the mononuclear variants in chemical and biological studies. Binuclear complexes with SBs have been widely studied as catalysts [79][80][81], in fluorescence and luminescence studies [82,83], and also antimicrobial activities were reported [84,85]. More recently, binuclear complexes with SBs have been suggested for the therapy of COVID-19 disease [86] on the basis of molecular modeling studies [87].
Dicopper(II) complexes are often used to study catecholase (or catechol oxidase) activity, a type-3 copper protein with a dicopper(II) moiety. Catecholase can reversibly bind oxygen at room temperature, thus it can be used to oxidize phenols to the respective obenzoquinones. Specifically, dicopper(II) complexes are often used to explore the catalytic activity of catecholase oxidation [88]. Recent studies on binuclear complexes with SBs are summarized in Table 3.       [95] ity, whereas carboplatin, used as a standard, exhibited no anticancer effect towards this cell line at the same concentration range within 24 h of incubation.
Keshavarzian et al., (2022) [93] described a study on a dimetallic complex with copper (II) and gadolinium (III). The Cu(II)-Gd(III) SB complex (35) was studied for its binding affinity with FS-DNA, by several analytical methods, and intercalation was suggested as the main mode of binding. The interaction with Bovine serum albumin (BSA) was also studied demonstrating a strong complexation. Antiproliferative activity was carried out by the MTT assay towards MCF-7, HeLa, and human prostate cancer (LNCaP) cancer cell lines. Finally, the mechanism and kinetics of the catalytic activity of the complex in the oxidation reaction of 3,5-di-tert-butylcatechol, was studied at 298 K. The complex exhibited moderate catecholase activity in DMF medium.
Savcı et al., (2022) [94] described the study of three dinuclear metal complexes with SBs, with Cu(II), Ru(II), and Pd(II) as metals, and their antiproliferative activity against human colon cancer (Caco-2) and fibroblast cells (L-929) evaluated via the MTT assay, compared to the reference drug 5-fluorouracil (IC 50 = 60.2 and 94.35 µM, respectively). The Cu(II) and Pd(II) complexes (36 and 37, respectively) showed a better cytotoxic effect against Caco-2 cells than the reference drug. Moreover, antioxidant studies were carried out via DPPH and ABTS assays, and the Pd(II) complex scavenged DPPH radicals close to the standard antioxidants (BHA, 70.19% and BHT, 44.71%), followed by the Cu(II) complex that scavenged the ABTS radicals in a better way (BHT, 85.16%; BHA, 84.7%). It is noteworthy that the antiproliferative effects of the complexes, as well as for the 5-fluorouracil, were significantly enhanced when used in combination with electroporation, resulting in a significant reduction of Caco-2 cancer cell viability.
Jahromi et al., (2022) [95] described a binuclear water-soluble Cu(II) complex [Cu II 2 L(µ 1,1 -NO 3 )(µ-OH)(NO 3 )(H 2 O), (38)], where L = [2,6-bis{N-(2-pyridylethyl)formidoyl}-4-methylphenol], which involves the µ-phenoxo N 2 O 4 SB ligand. The structure was determined, and it was evidenced by binuclear Cu(II) ions located in a six-coordinated distorted environment. The interaction of the complex with FS-DNA/BSA was investigated by several analytical techniques, revealing that the complex interacted with DNA in both UV-Vis absorption and a competitive binding experiment with ethidium bromide and revealed an intercalation mode (K b = 2.78 × 10 4 M −1 ). In Tris-buffer, the complex emitted relatively weak luminescence and increasing DNA concentration, a remarkable increase in fluorescence intensity of about two folds and a strong green fluorescence was observed by the naked eye, demonstrating that the complex behaves like a "light switch" for DNA in water. The antiproliferative effect of the complex was studied against three cell lines, including LNCaP, HeLa, and MCF-7, by MTT assay and was time-dependent and significantly lowered after the treatment with the complex (in Table data after 72 h). Moreover, the efficiency of the complex was studied for catecholase activity toward the oxidation of 3,5-di-tert-butylcatechol (3,5-DTBC) to 3,5-ditert-butylquinone (3,5-DTBQ) in acetonitrile and DMF by the UV-vis method. The complex showed high activity in catalyzing the oxidation of 3,5-DTBC to 3,5-DTBQ in acetonitrile.

Summary
SBs-metal complexes represent a fascinating and relevant research topic that continuously brings new information on newly synthesized compounds, which are usually inexpensive, easy to synthesize, and show numerous activities in a wide number of research fields. For instance, interesting biological activities have been found as antimicrobials, antiproliferative, and antioxidants, but other activities, such as anti-inflammatory, antimalarial, antidiabetic, and anti-Alzheimer have also been reported. The multiple activities are mostly due to the presence of the C=N linkage in the azomethine derivatives, but the wide range of applications is a consequence of the versatility of SBs reactions with several metals. This review presents an update of the most recent studies on mononuclear and binuclear metal complexes with SBs, focusing primarily on antimicrobial activity, which is one of the most important issues to date for overcoming antimicrobial resistance. Moreover, recent studies of these complexes as antimalarials and antidiabetics and as promising agents for the ever-present Alzheimer disease have also been described.