Metal complexes provide a rich platform for being used as therapeutic agents. Transition metals show variable oxidation states and an array of coordination geometries with different ligands. The ligands can alter the reactivity of the metal and also play a significant role in determining the nature of secondary coordination sphere interactions which involve recognition of biological targets such as enzymes, protein receptors, and DNA [25]. Schiff-based thiosemicarbazones are a versatile class of ligands, and their complexes have been used as therapeutic agents since long [30, 36]. Thiosemicarbazone-based metal complexes have been used as antineoplastic, antibacterial, antiviral, and antifungal agents [12, 20]. They are usually prepared by the condensation reaction between aldehydes or ketones with thiosemicarbazide [5]. Thiosemicarbazones as ligands show polydentate nature giving rise to a great variety of coordination modes [4]. The coordination ability of the basic ligand moiety can be enhanced by adding additional functional groups making them suitable for chelation [24]. Medical applications of thiosemicarbazones began to appear in the 1950s against tuberculosis and leprosy. In the 1960s, their antiviral properties were discovered, and after a considerable amount of research, methisazone and Marboran® were commercialized to treat smallpox [3, 23, 27]. Enhancement in activity can be obtained by optimization of the structure, which can result in groundbreaking discovery of new drug compounds [22]. It has been observed that coordination to a metal ion almost systematically increases the activity or contributes to mitigate the side effects of the organic parent compounds [14]. The major known effects related to the anticancer activity of thiosemicarbazone complexes include inhibition of ribonucleotide reductase (RR) [6], reactive oxygen species (ROS) production [38], topoisomerase II inhibition [17], mitochondrial disruption [43], and more recently, a multidrug resistance protein (MDR1) inhibition [31, 41]. The gray zone between chemistry and molecular biology further needs to be elucidated.

Materials and methods

Molecular docking was performed using Auto Dock Tools (ADT) version 1.5.6 and Auto Dock version 2.0. The structures of receptors topoisomerase II (PDB ID: 5IWI) and ribonucleoside diphosphate reductase (PDB ID: 5CI3) were downloaded from protein data bank ( IR spectra were recorded on a Bruker vertex 70 IR spectrophotometer in the frequency range 4000–500 cm−1. The samples were run as their KBr pellets. 1H NMR spectra were recorded on a Bruker spectrophotometer on 500.1 MHz at 295 K in the range of 0–10 δ using tetramethylsilane (TMS) as an internal standard. The samples were run in CDCl3 and dimethyl sulfoxide (DMSO)-d6, and chemical shifts were given relative to TMS (Merck) in ppm. UV spectra were recorded on a SpectraMax-5 spectrophotometer (Molecular Devices) in the range 200–400 nm. Mass spectrum of ligand was recorded on FAB-MS, JEOL SX-102. The conditions applied were as follows: ion source: ESI, positive; temperature 350 °C; nebulizer pressure 45 psi (N2); fragmenter voltage 130 V; capillary voltage 4000 V, and scan range m/z 100–700 (cycle time 800 ms). For chemical syntheses, all chemicals and solvents were of analytical grade and purchased from commercial sources. Hydrated salts of metals, i.e., CuSO4.5H2O, ZnSO4.7H2O, CoCl2.6H2O and FeSO4.7H2O, were used for complex formation. Melting points were assessed in Ambassador electrical melting point apparatus up to 400 °C by the open glass capillary method. Conductivity measurements were made on an EI Deluxe conductivity meter, Model-601, in DMSO (1.0 × 10−3 mol). For biological activity evaluation, 0.4% Trypan blue, PBS (pH = 7.2, 1×), 0.25% trypsin-EDTA (1×), DMEM/F-12 (1×) (Dulbecco’s modified Eagle’s medium), and antibiotic/antimycotic solution (100×) were obtained from Gibco, Life Technologies, whereas fetal bovine serum (FBS) and MTT were from HiMedia. DMSO was purchased from Calbiochem. MDA-MB-231 (human breast carcinoma, ER, tumorigenic and invasive), abbreviated as MDA cells, and A549 (lung carcinoma epithelial cell line) were obtained from the National Centre for Cell Science (NCCS), Pune, India. All other chemicals used in the biological activity study were of analytical grade.

Molecular docking studies

The synthesized ligand and metal complexes were subjected to molecular docking studies using the Auto Dock Tools (ADT) version 1.5.6 and Auto Dock version 2 docking programs (interactive molecular graphics programs) to understand the drug molecule interaction with topoisomerase II and ribonucleotide diphosphate reductase (RR) enzymes to investigate the potential binding mode and energy.

Toxicity potential assessment

Toxicity risk assessment gives an idea about the probable side effects of synthesized compounds that may be used for further processing in drug development and discovery. The mutagenic, tumorigenic, irritant, and reproductive toxicities were measured by means of precomputed set of structural fragments. The prediction of different properties of molecules in the early stage is a vital step in the drug discovery and development process. Toxic parameters of the ligand and complexes were generated by OSIRIS Data Warrior Software.

Bioactivity score prediction

Drug score values indicate overall potential of a compound to be a drug candidate. Mol inspiration is a web-based tool used to predict the bioactivity score of the synthesized compounds against regular human receptors such as GPCRs, ion channels, kinases, nuclear receptors, proteases and enzymes [34].

Evaluation of drug likeliness based on Lipinski’s rule of five

Lipinski’s rule of five is helpful in describing molecular properties of drug compounds required for estimation of important pharmacokinetic parameters such as absorption, distribution, metabolism, and excretion. The rule is helpful in drug design and development [13, 28, 40].


Synthesis of 2-butanone thiosemicarbazone

The ligand was prepared using a previously reported procedure with some modifications [26]. Reaction was monitored by TLC in CHCl3, Rf value (0.514). Mass spectrometry data confirmed the structure of ligand as indicated by molecular ion peak (M+1) corresponding to its molecular formula C5H11N3S. Yield 90%; MW 145; MP (°C) 99 °C; FTIR (KBr) (cm−1) 1609 (C=N), 761, 1077 (C=S); 1H NMR (MeOD) (MHz) 1.1 (t-3H), 1.9 (s, 3H), 2.3 (q, 2H), 3.3 (s, 1H,NH), 4.9 (s, 2H,NH2); 13C NMR (DMSO) (δ) 10.70 (CH3), 18.72 (CH3), 31.62 (CH2), 155.5 (C=N) and 178.72 (C=S); ESI MS (m/z) 146.1 M+; solubility: ethanol, DMSO, DMF; λ max (nm) 267.

Synthesis of metal complexes

Hydrated AR-grade metal salts were used for the preparation of metal adducts. The complexes were synthesized in 1:2 (metal-ligand) molar ratios through a general preparatory route. After refluxing the ethanolic solution of ligand with the aqueous solution of metal salts, colored precipitate was obtained which was filtered under vacuum. The precipitate was washed with ethanol and dried in a desiccator. The Co(II) salt was first oxidized to (III) state by using a few drops of conc. HNO3 as an oxidizing agent.


Yield 38%; MW 450; MP (°C) 195; FTIR (KBr) (cm−1) 1562 (C=N), 705, 1058 (C=S); 1H NMR (DMSO) (ppm) 0.31 (t, 3H), 2.3 (s, 3H), 2.5 (q, 2H), 6.6 (br s, 1H,NH), 7.8 (br s, 2H,NH2); Solubility DMSO, DMF; λ max (nm) 299; molar conductance 12.78 Ω−1 cm−1 mol−1.


Yield 23%; MW 442; MP (°C) 190; FTIR (KBr) (cm−1) 1562 (C=N), 705, 1050 (C=S); 1H NMR (DMSO) (ppm) not obtained as 1H NMR spectrum of the Fe(II)-thiosemicarbazone complex system is difficult to detect due to high spin state of Fe(II) in its complex [9, 15, 37]; solubility: DMSO, DMF; λ max (nm) 300; molar conductance 19.68 Ω−1 cm−1 mol−1.


Yield 62%; MW 452; MP (°C) 250; (KBr) (cm−1) 1570 (C=N), 705, 1050 (C=S); 1H NMR (DMSO) (ppm) 1.1 (t, 3H), 1.9 (s, 3H), 2.5 (q, 2H), 7.3 (br s, 1H,NH), 7.5 (br s, 2H,NH2); solubility: DMSO, DMF; λ max (nm) 300; molar conductance: 8.08 Ω−1 cm−1 mol−1.


Yield 46%; MW 420; MP (°C) 210; FTIR (KBr) (cm−1) 1570 (C=N), 700, 1050 (C=S); 1H NMR (DMSO) (ppm) 1.1 (t-3H), 2.2 (s,3H), 2.5 (q, 2H), 7.6 (br s, 1H,NH), 8.3 (br s,2H,NH2); solubility DMSO, DMF; λ max (nm) 320; molar conductance 105.04 Ω−1 cm−1 mol−1.

Biological activity evaluation

MDA-MB-231 and A549 cell lines were maintained by subculturing and passaging as monolayers in 25- and 75-cm2 cell culture flasks (Nest, Tarsons) at 37 °C in Tissue and Cell Culture Lab, Era’s Medical College, Lucknow, in a 5% CO2 incubator at 95% humidity for producing HCO3 buffering capacity as reported earlier [21]. The cells were maintained at pH 7.4 in DMEM containing phenol red as a pH indicator and supplemented with 5% FBS [21]. The medium, prior to being used in cell culture experiments, was vacuum filtered using a Corning filtration system (Corning®, Sigma-Aldrich).

Anticancer activity

Solutions (0.1 M) of the ligand and its four complexes were prepared in 1.0 mL 50% DMSO solution. The solutions were diluted ten times in DMEM to give 0.01 M (104 μM) solutions. In separate experiments, cells were trypsinized and cultured in a six-well plates (0.5 × 105 cells/well) initially for 24 h, so as to allow the cells to adhere. After 24 h of incubation, the cells were exposed to 20–100 μM of the ligand and its complexes for the next 48 h. Suitable untreated controls (containing 50% DMSO as vehicle) were also concomitantly employed. Each dose was tested in at least three replicate wells. For morphological analysis, cells in six-well plates were observed under a phase contrast microscope (Nikon Eclipse Ti, Japan) and photographed.

Cell viability/cytotoxicity analysis

  1. 1.

    Cell viability analysis using Trypan blue dye exclusion assay

To determine the cell viability, cells exposed to varying concentrations of the ligand and its synthesized complexes were subjected to Trypan blue assay. Briefly, cell suspensions were made at a suitable dilution (105cells/mL) in PBS. Respective cell suspensions (50 µL) were taken and mixed with an equal volume of 0.4% Trypan blue, mixed thoroughly and allowed to stand for 5 min at room temperature. Solution (50 µL)was transferred to a hemocytometer and viable cells were counted as clear cells and dead cells as blue ones. The number of live cells in both treated (ligand and its complexes) and control (cells and vehicle) wells was used for calculating the percentage cytotoxicity as % Cytotoxicity = Live Cell No. in Treated Wells − Live Cell No. in Control Wells/Live Cell No. in Control Wells × 100).

  1. 2.

    Methyl tetrazolium-MTT assay

    MTT was performed as per published protocol [33] in 96-well microtiter tissue culture plates (Linbro, MP Biomedicals). For MTT assay, 104 MDA cells were seeded in 200 μL of medium in a 96-well microtiter tissue culture plate and cultured in a humidified 5% CO2 incubator at 37 °C for 24 h. Defined concentrations (20–100 μM) of the ligand and its complexes in 50% DMSO were freshly prepared in culture media by serial dilution. Serial dilution was carried out in cell culture media in such a way that the final concentration of DMSO in the well did not exceed 0.5% (v/v). Three control wells containing the medium alone to serve as blanks were also included. After 24 h of incubation, in separate experiments, cells were treated with the previously mentioned concentrations of the ligand and its four complexes in triplicates for 48 h. Equal volumes of 50% DMSO (in cell culture media) were used as vehicle controls. At the end of treatment, cell culture medium containing varying amounts of ligand/complexes was removed and 20 μL of MTT (stock made in PSS at 5.0 mg/mL) reagent was added to each well and incubated for 4 h. Thereafter, MTT was removed and formazan crystals were dissolved in 200 μL of DMSO. The plates were read in a Bio-Rad PW41 ELISA plate reader at a wavelength of 570 nm with a reference wavelength of 630 nm. Percentage cell viability (Y-axis) was calculated from absorbance and plotted against concentration in micromolar (X-axis).

    % Cell survival was calculated as = {(A T − A B)/(AC − A B)} × 100 where

    A T = Absorbance of treatment well.

    A B = Absorbance of blank.

    Ac = Absorbance of control well.

    % cell inhibition = 100 − Cell Survival.

    IC50 values were obtained from the graph as the concentration, which decreased cell by viability 50%.

Antibacterial activity

The in vitro antibacterial activity of the ligand and its complexes was evaluated against Staphylococcus aureus (Gram-positive) and Escherichia coli (Gram-negative) bacteria by the disc diffusion method [1] using Mueller-Hinton agar (MHA) medium. The bacteria were subcultured in the agar medium and were incubated for 24 h at 37 °C. The discs (sterile filter paper discs, Whatman No. 1.0), having a diameter of 5 mm, were then soaked in the test solutions with the appropriate equivalent amounts of the ligand and its four complexes dissolved in sterile 50% DMSO at concentrations of 2–10 mg/disc and placed on lawn culture of the respective microbial organism and stored in an incubator for the previously mentioned period of time. Formation of inhibition zone (if any) around each disc was measured, and the results were recorded in the form of inhibition zones as a function of diameter (mm). To clarify any effect of DMSO (used as a vehicle for the dissolution of the ligand and its complexes) on biological screening, 50% DMSO was used as negative control where it showed no activity against any bacterial strains. Tetracycline was used as a positive control.

Data interpretation and statistical analysis

Absorbance values that were lower than the control wells indicated a reduction in the rate of cell proliferation. Conversely, a higher absorbance value indicated an increase in cell proliferation. Rarely, an increase in proliferation might be offset by cell death; evidence of cell death was inferred from morphological analysis. Results were expressed as mean ± SD of experiments done in duplicates.

Results and discussion

Computational docking is an extremely useful tool to gain an understanding about synthesized compounds and their interactions with biological drug targets, which is very important in drug discovery research. The Molecular Docking software predicted the amino acids in active site region of the studied target proteins.

Docking with topoisomerase II

Calculated binding energies and inhibition constants (Ki) of 2-Butanone Thiosemicarbazone and its Fe(II) and Zn(II) complexes with respect to the enzyme and the interacting amino acids in its active site have been summarized in Table 1. Fe (II) complex was found to have minimum binding energy (-5.08 kcal/mol) released on interaction with target protein (Topo II) and also the lowest Ki value (188.07 µM) as compared to the Zn (II) complex and ligand. The docking interactions of the ligand and its Fe(II) and Zn(II) complexes with Topo II have been shown in Fig. 1a–c.

Table 1 Docking results with Topo II (PDB ID: 5IWI)
Fig. 1
figure 1

Docking pose of ligand (a), its Fe complex (b), and Zn complex (c) in the active site of Topo II

Docking with ribonucleotide diphosphate reductase

Calculated binding energies and inhibition constants (Ki) of the ligand and its Fe(II) and Zn(II) complexes with respect to the enzyme RR and the interacting amino acids in its active site have been summarized in Table 2. The interactions between the drug compound and the active sites on the target receptors may be through non-covalent interactions like hydrogen bonding, hydrophobic, and van der Waals interaction [10]. Zn (II) complex had a lower binding energy (-4.42 kcal/mol) and lower Ki value (571.48 µM) with respect to RR as compared to Fe (II) complex.The docking interactions of the ligand and its Fe(II) and Zn(II) complexes with RR have been shown in Fig. 2a–c.

Table 2 Docking results with RR (PDB ID: 5 CI3)
Fig. 2
figure 2

Docking pose of ligand (a), its Fe complex (b), and Zn complex (c) in the active site of RR

Characterization and complex formation

Preparatory scheme of the ligand and metal complexes is given in Fig. 3. Spectral analysis confirmed complex formation. 1H NMR spectrum of the ligand revealed that NH and NH2 protons were observed downfield due to higher electronegativity of nitrogen making the attached protons de-shielded. On complexation, the frequencies further got down field (7–8 ppm) due to electronegativity difference between the metal ion and nitrogen. In the 13C spectrum of ligand, the thiol carbon peak (C=S, 178.72) and the carbon attached to nitrogen (C=N, 155.5) were found to be the most downfield because of electronegativity difference. The 1H NMR spectrum of the Fe(II) thiosemicarbazone complex (t2g4, eg 2 system) was difficult to detect due high spin state of the Fe(II) complex. In order to characterize d6 Fe-thiosemicarbazone complex, the signal of protons centered at 0 to 10 ppm was found to be very broad and difficult to distinguish from the baseline, thereby making it not useful for monitoring the existence of the Fe(II) complex [9, 15, 37]. Mass spectrum data gave a molecular ion peak (M+1) at 146 corresponding to its molecular weight of 145. The bonding mode of the ligand to metal ion was elucidated by analysis of the IR data. By comparing the frequencies of the ligand with the metal complexes, it was concluded that ligand coordinates with the metal centre through the azomethene nitrogen [11, 19] and the thione sulfur [7, 42], hence indicating the bidentate nature of the ligand because the C=N and C=S frequencies decrease in case of metal complex formation. The ligand may show thione-thiol tautomerization because it has a thiomide functional group. However, the absence of v (S–H) stretching in 2500–2600-cm−1 region of the IR spectrum of the ligand indicated that the ligand retained its thione form in the solid state. In addition, the band at 1119 cm−1 found in ligand was found to be missing in complexes. Appearance of new bands at 1058 cm−1 (Cu (II) complex), 1050 cm−1 (Co (III) complex, 1050 cm−1 (Fe (II) complex), and 1050 cm−1 (Zn (II) complex) confirmed the fact that there was a contribution of C=S vibration in this region. Bands higher than 1080 cm−1 disappeared in complexes [16]. 1H NMR data provided information about the different positions of protons. In the 1HNMR spectra of the complexes, a high-frequency shift of the methyl hydrogen atoms (C–CH3), vis-à-vis ligand spectrum, gave evidence that coordination occurred through the azomethine nitrogen atom [39]. High melting points of the complexes were another indication of coordination. λ max of the ligand (267 nm) corresponded to π–π* transition [2], whereas in complexes, the absorption maximum between 285 and 385 nm was assigned to n–π* transition [8, 18]. Increase in absorbance (hyperchromic shift) in all the complexes was attributed to complexation behavior of ligand towards metal ions confirming the coordination of the ligands to the metal ions.

Fig. 3
figure 3

Synthesis scheme

Conductivity measurements can predict the mode of coordination of counter ions to metal complexes. They provide a method of testing degree of ionization of the complexes. The larger the number of ions outside the coordination sphere, the greater would be the molar conductance [35]. Low molar conductivities of the Cu(II), Zn(II), and Fe(II) butanone thiosemicarbazone complexes were indicative of non-electrolytic nature indicating the bonding of sulfate ions to the metal ions [32]. Co(III) complex showed higher molar conductance of 105.04 Ω−1 cm−1 mol−1, which may be due to positive charge over the coordination sphere. The Fe, Cu, and Zn complexes dissolved in DMSO and DMF with time whereas Co complex dissolved readily further confirming its electrolytic nature. The solubility difference can be explained on the basis of different salts used for the synthesis having sulfate and chloride as anions.

$$ n=+1\ \mathrm{in}\ \mathrm{case}\ \mathrm{of}\ \mathrm{Co}\ \left(\mathrm{III}\right)\ \mathrm{complex},\mathrm{A}={{\ \mathrm{SO}}_4}^{2-}{\mathrm{or}\ \mathrm{Cl}}^{-} $$

Toxic parameters of the complexes

The parameters predict the probable side effects of the compounds. The synthesized ligand and complexes were predicted to have no side effects as shown in Table 3.

Table 3 Toxicity potential of the ligand and its complexes

Bioactivity score prediction

The pharmacological activity describes the beneficial effects of drugs in living beings. The drug is supposed to bind with a biological target. Biological targets are the most common proteins such as enzymes, ion channels, and receptors. The biological target is also referred to as drug target. The bioactivity scores of the synthesized complexes were calculated for different parameters such as binding to G protein-coupled receptor (GPCR) ligand and nuclear receptor ligand, ion channel modulation, kinase inhibition, protease inhibition, and enzyme activity inhibition. All the parameters were calculated with the help of online software Molinspiration (, which predicted moderate biological activity for the synthesized complexes. The bioactivity score is given in Table 4. It is known that for metal complexes, if the bioactivity score is more than 0.0, then the complex is active; if it is between −5.0 and 0.0, then the complex is moderately active, and if the bioactivity score is less than −5.0, then it is inactive. As seen in Table 4, the bioactivity scores of the ligand as well as all the four complexes were between −5.0 and 0.0, which clearly indicate that they possess such properties as are required for the complexes to act as potential drugs with some modifications in chemical structure [10].

Table 4 Bioactivity score of the ligand and its complexes

PASS Analysis: Lipinski’s parameters

Lipinski’s rule of five (RO5) is used to evaluate drug likeliness of a chemical compound possessing properties that would make it a likely or potential drug in humans [29]. The oral activity of a drug compound is predicted by calculating certain molecular parameters like log P (partition coefficient), polar surface area, number of hydrogen bond donors, number of hydrogen bond acceptors, and molecular weight. The rule states that most metal complexes with good membrane permeability have log P ≤ 5, number of hydrogen bond acceptors ≤10, and number of hydrogen bond donors ≤5 [10]. In general, an orally active drug has no more than one violation of the given criteria. In the present study, the synthesized ligand and its complexes were found to be in good agreement with the given criteria and can be said to possess good oral bioavailability (Table 5).

Table 5 Physicochemical properties of the synthesized ligand and its complexes

Biological evaluation of ligand and complexes

  1. 1.

    Morphological analysis

Suppl. Figs. 1-10 (a-l) respectively depict the dose-dependent effect of the ligand and its four complexes on MDA and A549 cells using phase contrast microscopy. Ligand was found to be active against MDA cells in the tested range. No significant activity of the ligand was detected in the tested range against A549 cells. However, all complexes were found to possess significant activity against both cell lines with IC50 values of <50 μM (refer to Suppl. data).

  1. 2.

    Cell viability analysis

Suppl. Tables 1-5 present the dose-dependent cytotoxicity of the ligand and its complexes when tested in the range of 20–100 μM against breast cancer cells MDA-MB-231 and lung carcinoma cells A549 cells using the Trypan blue dye exclusion assay. As mentioned before, ligand did not exhibit any activity against A549 cells whereas its complexes displayed significant cytotoxicity against both the tested cell lines. Results were expressed as mean ± SD of experiments done in duplicates (refer to Suppl. data).

  1. 3.

    MTT assay

Figures 4 and 5 respectively depict the dose-dependent effect of the ligand (Figs. 4a and 5a), its Co (Figs. 4b and 5b), Fe (Figs. 4c and 5c),Cu (Figs. 4d and 5d) and Zn (Figs. 4e and 5e) on MDA and A549 cells using the MTT assay. Ligand showed 50% cytotoxicity against MDA at 80 μM (IC50 value approx. 80 μM). As mentioned earlier, the ligand did not show any significant activity against A549 cells within the tested range. However, complexation with metals significantly increased the cytotoxicity of the ligand against both cell lines.

Fig. 4
figure 4

ae Dose-dependent effect of ligand (a), its Co (b), Fe (c), Cu (d), and Zn (e) complexes on viability of MDA cells in vitro using MTT assay. Final concentration of DMSO in each well did not exceed 0.5% (v/v). Results were expressed as mean ± SD of experiments done in triplicates.

Fig. 5
figure 5

ae Dose-dependent effect of ligand (a), its Co (b), Fe (c), Cu (d), and Zn (e) complexes on viability of A549 cells in vitro using MTT assay. Final concentration of DMSO in each well did not exceed 0.5% (v/v). Results were expressed as mean ± SD of experiments done in triplicates.

Antibacterial activity

The ligand together with its complexes was also evaluated for their potential antibacterial activity against S. aureus and E. coli. The ligand did not exhibit any significant activity against both species. However, Co and Cu complexes exhibited mild antibacterial activities against S. aureus (Fig. 6, Table 6), whereas Cu complex alone showed moderate activity against E. coli (Fig. 7, Table 7).

Fig. 6
figure 6

Antibacterial activity of ligand (a), its Co (b), Fe (b), Cu (c), and Zn (d) complexes against S. aureus using disc diffusion method

Table 6 Comparison of MIC values (in mg/mL) of ligand and its complexes and standard antibiotic tetracycline against S. aureus
Fig. 7
figure 7

Antibacterial activity of ligand (a), its Co (b), Fe (b), Cu (c), and Zn (d) complexes against E. coli using disc diffusion method

Table 7 Comparison of MIC values (in mg/mL) of ligand and its Co and Fe complexes and standard antibiotic tetracycline against E. coli


The overall activity spectrum of biologically active compounds can be predicted by computational analyses like molecular docking with probable receptors or by prediction of bioactivity score and physicochemical properties. In this paper, anticancer and antibacterial activities of ligand 2-butanaone thiosemicarbazone and its four metal complexes have been reported against two cancer cell lines and two species of bacteria. While the ligand displayed mild anticancer activity against MDA cell line (80 μM) and none against A549 cell line, its four complexes displayed significant anticancer activities against both the tested cell lines with IC50 <50 μM for Co, Fe, and Zn complexes. However, only Cu complex exhibited appreciable activity against S. aureus and E. coli while Co complex was found to be mildly active against S. aureus only. Molecular docking studies showed significant binding of the ligand with selected targets. Bioactivity score and PASS analysis showed that the metal complexes can have potential inhibitory action against the selected cell lines. The study has shed light on the role of different anions on the overall solubility of the complexes, which can also affect their conductivity. Likewise, the oxidation state of metal significantly influences its affinity for a particular ligand working on the hard-soft acid-base concept. This phenomenon would be explored in more detail in future. In future, the complexes of ligand would be tested against other cancer as well as normal cell lines and would also be evaluated for their probable anticancer and antibacterial activities in vivo. The complexes would also be analyzed for their potential antioxidant and DNA cleavage activity.