Antimicrobial activity of novel synthesized coumarin based transitional metal complexes.

OBJECTIVES: To synthesize new transitional metal complexes derived from 3-aryl-azo-4-hydroxy coumarin analogues and to evaluate their antimicrobial activities.
METHODS: The syntheses of complexes of coumarin analogues were accomplished by mixing a hydro-alcoholic solution of 3-aryl-azo-4-hydroxy coumarin analogues with transition metal chlorides. The structural environment of the synthesized molecules was characterized using different instrumental methods. The antimicrobial activity of the compounds was determined by the agar well diffusion method.
RESULTS: The cobalt complexes of (E)-3-((4-chlorophenyl) diazenyl)-4-hydroxy-2H-chromen-2-one (HL1): (4a) and (E)-3-((4-methoxyphenyl) diazenyl)-4-hydroxy-2H-chromen-2-one (HL2): (4e) showed excellent antimicrobial activities compared with their ligands.
CONCLUSION: The reports of the antimicrobial investigation showed that the cobalt complexes of 3-aryl-azo-4-hydroxy coumarin analogues exhibited potential antimicrobial activity that was stronger than that of their ligands.

Introduction

Due to the increasing number of multi-drug-resistant microbial pathogens and the inclusion of emerging infectious diseases such as severe acute respiratory syndrome and avian influenza, the treatment of microbial infections still remains a challenging job with the available antimicrobials and remains a worldwide problem for clinical management. Development of newer molecules with less expense and minimum toxicity for the management of infections due to multi-drug-resistant (MDR) microbial pathogens should represent the vital sphere of antimicrobial research today. A literature survey revealed that azo molecules are popular for versatile uses such as antiseptics, antimicrobial, antidiabetics, antineoplastics, transmissible spongiform encephalopathy, antiulcerative, antoxidant, analgesic, antiinflammatory, antiviral, antitubercular and antitumour activities.

A literature survey also revealed that azo-bearing ligands have a modified therapeutic effect when combined with transition metal ions.13, 14 The complexes of transition metals have significant biological functions including antibacterial, antifungal and anticancer activities. Cobalt, copper, nickel and zinc are the potentially used metal ions that form low-molecular-weight complexes, which are found to be effective against various diseases. Literature support even suggests that metal complexes are more active than their ligands because the metal complexes serve as a vehicle for activation of the ligands as principal cytotoxic species.16, 17

The biological aspects of metallic ligands depend upon the ease of cleaving the bond between the metal ion and the ligand. It is well known that the metals present in complexes generally accelerate the drug action and the efficacy of therapeutic agents and that the pharmacological efficiencies of drug-based metal complexes depend upon the nature of the metal ion and the ligands. The present work is the continuation of our previously reported work to obtain some novel complexes where the 4-chlorophenyl and 4-methoxyphenyl substituted 4-hydroxycumarin azo-analogues are conjugated with different transitional metals with an intention to produce target molecules possessing good antimicrobial properties.3, 19

Materials and Methods

All the chemicals used in the present studies were of synthetic grade and were obtained from Merck specialties Ltd. and HiMedia laboratories Pvt. Ltd, (Mumbai, India). The prepared products were analysed by FT/IR (JASCO FT/IR 4100 Spectrophotometer) using KBr pellets. An LC-MS column C6 (150 mm × 4.6 mm) with a 5 μm particle size (Shimadzu-Mass spectrophotometer) was used. The 1H NMR spectra were recorded on a Bruker 1H NMR 400 MHz using tetramethylsilane as an internal standard, and the chemical shifts were reported in δ ppm. The UV (Jasco V-630 Spectrophotometer) and elemental analyses for C, H, N and S were performed on a Perkin Elmer model 2400 CHNS/O analyser. A Shimadzu XRD 7000 was used for the study of the structural environment of the synthesized ligands and their metal complexes. The Faraday balance technique was employed for the measurement of magnetic susceptibility of the metal complexes. The in vitro antimicrobial activities against different bacterial and fungal pathogens were determined by the agar well diffusion method, sourced from IMTECH, India, Chandigarh.

Synthesis of ligands (3a–3b)

The synthetic procedures yielding the ligands (E)-3-((4-chlorophenyl) diazenyl)-4-hydroxy-2H-chromen-2-one (HL): (3a) and (E)-3-((4-methoxyphenyl) diazenyl)-4-hydroxy-2H-chromen-2-one (HL): (3b) were carried out as described previously.

Synthesis procedure of metal complexes (4a–4h)

A mixture of 25 mL was prepared with the appropriate metal chloride (Cu(II), Ni(II), Co(II) and Zn(II) of 10 mmol in ethanol and water, 1:1). The above mixture was added to the solution of azo compound 3a–3b (0.40 g, 10 mmol) in ethanol and water in equal proportions to obtain 50 mL of solution. The resulting solution was refluxed for 30 min at a controlled temperature not more than 78 °C. The precipitated complexes were separated by filtration using Whatman filter paper. Separated precipitates were washed with 1:1 ethanol-water. Finally, obtained products were re-crystallized from diethyl ether and air dried.

Spectral characterization

(E)-3-((4-chlorophenyl)diazenyl)-4-hydroxy-2H-chromen-2-one (HL1), (3a)

Off yellow-coloured powder; yield 91%; Rf: 0.7; m.p.: 235–40 °C; UV–Vis (λ max, DMSO): 409 nm; IR (KBr, ν, cm−1): 3445(O—H str.), 1619 (CC str.), 1500 (–NN–), 1726 (CO str.), 1298 (C—O str.), 828 (1, 4 disubst. Ar.); 1H NMR (DMSO-d, δ ppm, 400 MHz): 16.86 (s, 1H, 4-enolic OH), 7.65 (m, coumarin H-7), 7.45 (m, coumarin H-6), 7.47 (d, coumarin H-8), 7.90 (d, coumarin H-5), 7.21–7.39 (m, 4H, Ar—H); LC-MS (RT, % area); 2.291, 60.04 m/z; 301.2 (M+1); Analysis for C15H9ClN2O3: Calcd: C, 59.91; H, 3.02; N, 9.32; Found: C, 59.93; H, 3.04; N, 9.36%.

(E)-3-((4-methoxyphenyl)diazenyl)-4-hydroxy-2H-chromen-2-one (HL2), (3b)

Brick red-coloured powder; yield 93%; Rf: 0.8; m.p.: 205–10 °C; UV–Vis (λ max, DMSO): 413 nm; IR (KBr, ν, cm−1): 3479 (O—H str.), 2929 (CH2 str.), 1603 (CC str.), 1745 (–CO str.), 1505 (–NN–), 1487, 1113 (C—O—CH3 str), 1246 (C—O str.), 758 (1, 2 disubst. Ar.); 1H NMR (DMSO-d, δ ppm, 400 MHz): 16.81 (s, 1H, 4-enolic OH), 7.65 (m, coumarin H-7), 7.46 (m, coumarin H-6), 8.09 (d, coumarin H-5), 7.57 (d, coumarin H-8), 6.94–7.34 (d, 4H, Ar—H), 3.83 (s, 3H, Ar—OCH3); LC-MS (RT, % area); 2.291, 60.04 m/z; 297.0 (M+1); Analysis for C16H12N2O4: Calcd: C, 64.86; H, 4.08; N, 9.46; Found: C, 64.91; H, 4.11; N, 9.43%.

Nickel complex of (E)-3-((4-chlorophenyl)diazenyl)-4-hydroxy-2H-chromen-2-one (HL1), (4b)

Light green-coloured powder; yield 37%; Rf: 0.8; m.p.: 245–50 °C; UV–Vis (λ max, DMSO): 440 nm; IR (KBr, ν, cm−1): 1625 (CC str.), 1529 (–NN–), 1723 (CO str.), 1299 (C—O str.), 829 (1, 4 disubst. Ar.), 446 (Ni—N), 535 (Ni—O); 1H NMR (DMSO-d, δ ppm, 400 MHz): 7.71 (m, coumarin H-7), 7.36 (m, coumarin H-6), 7.38 (d, coumarin H-8), 8.11 (d, coumarin H-5), 7.26–7.33 {m, 8H, (C6H4)2; LC-MS (RT, % area); 1.147, 63.31 m/z; 654.01 (M+1); Analysis for C32H24ClN4NiO6: Calcd: C, 58.70; H, 3.69; N, 8.56; Ni, 8.56 Found: C, 58.68; H, 3.72; N, 8.58; Ni, 8.54%.

Cobalt complex of (E)-3-((4-methoxyphenyl)diazenyl)-4-hydroxy-2H-chromen-2-one (HL2), (4e)

Brown-coloured powder; yield 43%; Rf: 0.7; m.p.: 245–50 °C; UV–Vis (λ max, DMSO): 450 nm; IR (KBr, ν, cm−1): 3012 (Ar H), 2939 (CH2 str.), 1619 (CC str.), 1725 (–CO str.), 1525 (–NN–), 1488, 1115 (C—O—CH3 str), 1248 (C—O str.), 759 (1, 2 disubst Ar.), 449 (Co—N), 538 (Co—O); 1H NMR (DMSO-d, δ ppm, 400 MHz): 7.64 (m, coumarin H-7), 7.41 (m, coumarin H-6), 8.07 (d, coumarin H-5), 7.49 (d, coumarin H-8), 6.91–7.23 {m, 8H, (C6H4)2}, 3.82 {s, 6H, (OCH3)2}; LC-MS (RT, % area); 1.871, 51.04 m/z; 651.0 (M + 1); Analysis for C33H27CoN4O7: Calcd: C, 60.93; H, 4.18; N, 8.61; Co, 9.06 Found: C, 60.94; H, 4.15; N, 8.65, Co, 9.09%.

Antimicrobial activity

The above newly synthesized 4-HC azo-analogues and their metal complexes were investigated over different freshly sub cultured microbial strains, viz. Escherichia coli (MTCC 614), Klebsiella pneumonia (MTCC 109) and Candida albicans (MTCC 3017), that were procured from the Institute of Microbial Technology and Gene bank (IMTECH), Chandigarh, India. Staphylococcus aureus and Cryptococcus neoformans were obtained from the University Department of Pharmaceutical Sciences, Utkal University. Ampicillin and fluconazole were used as reference antibiotics.

The antimicrobial diffusion test was performed using a cell suspension of approximately 1.5 × 106 CFU mL−1 employing a McFarland turbidity standard No. 0.5. The antimicrobial activities of the novel 4-HC analogues (3a–3b) and the reported complexes (4a–4g) were determined by the agar well diffusion method using sterile molten nutrient agar (antibacterial activity) preparations of the compounds and Sabouraud dextrose agar (antifungal activity) preparations of compound 4d and their respective complexes.

Minimum inhibitory concentration (MIC)

A 1 mg mL−1 stock solution of each of the synthesized compounds and reference antibiotic was prepared using DMF. Further, five different concentrations (500–31.25 μg mL−1) were prepared by the serial dilution method. The different concentrations for the respective compounds were loaded into the wells and incubated at 37 °C for 18–24 h. After incubation, the MIC was determined.

Acute toxicity study

The experiment was carried under the guideline of the Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA) and approved by the Institutional Animal Ethical Committee (IAEC), School of Pharmaceutical Sciences. Siksha ‘O’ Anusandhan University, Bhubaneswar, Odisha, India, with registration number 1171/C/08/CPCSEA and Ref. No. 60/SPS/IAEC/SOAU. The said synthesized compounds were subjected to an acute oral toxicity study to establish their safety dose. Healthy young female Wister rats that were 8–12 weeks of age were selected. OECD guideline No. 420 (2000) for the acute oral toxicity fixed dose procedure of the test compounds (3a–3b and 4a–4h) was followed. To conduct the sighting study, a single animal was provided with suspensions of the synthesized compounds having a specific dose, viz. 5 mg, 50 mg, 300 mg and 2000 mg/kg body weight, with the aid of an intubation canula. A period of 24 h was maintained between each dosing. In the main study, another 4 animals were administered 2000 mg/kg. The animals were observed for a period of 14 days. However, the acute toxic symptoms and the behavioural changes produced by the test compounds were observed continuously at an interval of 4 h up to 24 h.

Statistical analysis

The observed data on the zone of inhibitions were subjected to a one way analysis of variance. The mean zone of inhibition for each compound on each strain was compared with the reference antibiotic through a Dunnett Post Hoc test (https://www.statstodo.com/SSizAOV_Pgm.php). The test of significance was performed at the 5% level of type one error. The research hypothesis was ‘the zone of inhibition for the test compound was higher than the reference antibiotics’ against the hypothesis of no difference (null hypotheses), which states that there is no significant difference between the zone of inhibition of the test compound and the reference antibiotics.

Sample size determination

A minimum sample size of five was calculated taking the probability of type 1 error (d) = 0.05, Power (1-β) = 0.8, Number of groups = 13 within group SD = 2. However, a sample size of six has been taken in the study for each compound against each strain.

Results

The metal complexes of 3-aryl-azo-4-hydroxy coumarin analogues were synthesized by refluxing different hydro alcoholic solutions of metal chlorides with 3-(4-chloro phenyl/4-methoxy phenyl)-azo-4-hydroxy coumarin analogues (Scheme 1) and finally re-crystallized from diethyl ether. The structures of the prepared compounds are confirmed by different instrumental methods of analysis. The physical characteristics of the synthesized compounds are reported in Table 1. The FT/IR spectra of synthesized ligands 3a and 3b showed strong vibration bands at 3479–3445 cm−1, 1619–1603 cm−1, 1726–1745 cm−1, 1298–1246 cm−1 and 1529–1505 cm−1 due to presence of functional groups such as OH str., CC str., CO str., C—O str. and NN str., respectively. The strong vibration bands of compound 3a at 1726, 1619 and 1298 cm−1 may be due to presence of a lactone carbonyl of CO str., CC str. and C—O str., respectively, and are illustrated in Figure 1. The frequencies of all the complexes (4a–4h) assigned at 1629–1613 cm−1, 1729–1721 cm−1, 1296–1248 cm−1 and 1529–1524 cm−1 correspond to CC str., CO str., C—O str. and NN str., respectively. The IR spectral bands of all metal complexes appearing at 451–441 and 538–531 cm−1 are assigned to (M−N) and (M−O), respectively. The 1H NMR spectra of the ligands showed a broad singlet at δ 16.81–16.86 ppm towards the presence of the enolic OH group of 4-hydroxy coumarin. The 1H NMR spectrum of compound 3b showed a sharp singlet at δ 3.83 ppm corresponding to the proton of –OCH3 (Figure 2). All of the complexes showed signals at a range of (6.90–7.26)–(7.23–7.37) ppm corresponding to {m, 8H, (C6H4)2}.

Scheme 1

Synthesis of coumarin based transitional metal complexes.

Table 1

Physical characteristic data of the synthesized 4-hydroxy coumarin analogues and their complexes.

Comps.	Substitution	M. formula	m/z (Calc)	m/z (Found)	Rf	M. P. (°C)	Colour	Yield (%)	UVλ maxDMSO	Elemental Analysis Cal. (Found)
										C	H	N
3a	4-Chlorophenyl HL1	C15H9ClN2O3	300.03	301.2	0.7	235–40	Off yellow	91	409	59.91 (59.93)	3.02 (3.04)	9.32 (9.36)
3b	4-Methoxyphenyl Hl2	C16H12N2O4	296.08	297.0	0.8	205–10	Brick red	93	413	64.86 (64.91)	4.08 (4.11)	9.46 (9.43)

Figure 1

FT/IR spectra of 3-((4-chlorophenyl) diazenyl)-4-hydroxy-2H-chromen-2-one (3a).

Figure 2

1H NMR spectra of 4-hydroxy-3-((4-methoxyphenyl)diazenyl)-2H-chromen-2-one (3b).

The magnetic susceptibility of the Co(II) complex is 5.09 BM, which is nearer to the reported value for octahedral symmetry. The Ni(II) complex showed a magnetic moment of 2.94 BM, whereas the Cu(II) complex showed a magnetic moment of 1.98 BM, suggesting an octahedral geometry. Compounds 3a–3b act as bidentate ligands by coordinating to the transitional metal ions through their azo and enolic hydroxyl moiety. Based upon the study of magnetic susceptibility values of the complexes, the probable structure is given in Scheme 1.

The predicted molecular weights of the synthesized compounds were confirmed by LC–MS and the results are summarized in Table 1. Compound 3a possesses a molecular ion peak at 301.2 m/z that strongly reveals the predicted molecular formula C15H9ClN2O3 that is reported in Figure 4.

Figure 4

LCMS of (E)-3-((4-chlorophenyl)diazenyl)-4-hydroxy-2H-chromen-2-one (HL1): (3a).

The UV spectroscopic analyses of the synthesized ligands and complexes revealed that complexes 4a and 4e demonstrated a good bathochromic shift at 463 and 450 nm, whereas ligands 3a and 3b possessed a λ max at 409 and 413 nm, respectively. The solvent effect of the ligands and their respective complexes are spectrally presented in Figure 3.

Figure 3

Solvent effect of the complexes of 3a its metal complexes (plate a) and 3b its metal complexes (plate b) using DMSO.

The X-ray diffraction (XRD) technique provides the most definitive structural information. The study of the XRD pattern of the synthesized complexes was performed using a Cu Kα X-ray source and a step of 0.02 (2θ) and run at 2θ = 2–80° using a Shimadzu XRD 7000 instrument at a scanning speed of 2.000 (deg/min). Using Origin data analysis software, the structures of the obtained complexes were interpreted. The pattern and the number of reflections reported in Figure 5 clearly declared the structural difference of compounds 4e and 4f.

Figure 5

XRD of 4e and 4f respectively in plate a & b.

The results of the antimicrobial activity of the newly synthesized 3-aryl-azo-4-hydroxy coumarin analogues and their complexes compared with reference antibiotics (RA) ampicillin and fluconazole (as antibacterial and antifungal standard drugs, respectively) expressed in mean ± SD are reported in Table 2. The reported results revealed that compounds 4a and 4e showed significant antimicrobial activity in comparison to standard drugs (p < 0.05) against E. coli, K. pneumonia, S. aureus, C. albicans and C. neoformans. All compounds except for 4d and 4h showed significant antibacterial activity against S. aureus. However, complex 4a showed highest mean zone of inhibition (mm) against K. pneumonia and C. neoformans, 19 ± 1.1 and 27.5 ± 1.64, respectively. The largest mean zones of inhibition exhibited by complex 4e against S. aureus and C. neoformans was 23 ± 2.28 and 28.17 ± 1.72, respectively. The anti-biogram pattern of compound 3a, 3b and their complexes against different fungal strains are illustrated in Figure 6. The graphical representation of complexes 4a and 4e is illustrated in Figure 7.

Table 2

Antimicrobial activity (Zone of inhibition in mm) of the newly synthesized 4-hydroxy coumarin analogues and their complexes against different microbial strains (Mean ± S.D.) at a concentration of 1 μg μL−1.

Comps.	E. colia	K. pneumoniab	S. aureusc	C. albicansd	C. neoformanse
3a	17.33 ± 1.63*	16.67 ± 2.42	15.33 ± 2.34	20.67 ± 1.86	25.17 ± 1.84
3b	19.17 ± 2.56*	18.5 ± 3.27	18.83 ± 1.47*	21.83 ± 1.84	26.83 ± 2.64*
4a	19.17 ± 2.4*	19 ± 1.1*	18.33 ± 2.34*	23.67 ± 2.16*	27.5 ± 1.64*
4b	19.17 ± 1.72*	18 ± 1.1	18.83 ± 3.25*	20.83 ± 2.56	14 ± 0.89
4c	–	14.17 ± 2.71	17.5 ± 1.64*	18.33 ± 1.63	26.67 ± 1.03*
4d	–	11.5 ± 0.84	12.67 ± 1.51	12.5 ± 2.35	11.5 ± 1.64
4e	21.17 ± 2.71*	21.17 ± 4.45*	23 ± 2.28*	25.5 ± 2.07*	28.17 ± 1.72*
4f	23.17 ± 2.23*	19.83 ± 4.07*	21.5 ± 1.76*	22.33 ± 3.27	15.83 ± 1.84
4g	–	14.83 ± 2.14	16.83 ± 2.71*	25.17 ± 1.6*	27 ± 2.1*
4h	–	12.33 ± 1.51	12.67 ± 2.25	13 ± 3.1	10.83 ± 1.33
RA	12.67 ± 1.51	15.33 ± 1.97	13 ± 1.67	19.33 ± 4.68	24.17 ± 1.94

Results are expressed as the Mean ± S.D. (n = 6). The data were analysed by one-way ANOVA followed by Dunnett's Post Hoc test. (Statistical significance at *p < 0.05 in comparison to RA (Reference Antibiotic): ampicillin (antibacterial); fluconazole (antifungal)); –, No zone of inhibition; a, Escherichia coli; b, Klebsiella pneumonia; c, Staphylococcus aureus; d, Candida albicans; e, Cryptococcus neoformans.

Figure 6

Antifungal activity of 3a its metal complexes (plate a) and 3b its metal complexes (plate b) against C. neoformans and C. albicans respectively.

Figure 7

Graphical presentation of antimicrobial activity of 4d and 4e.

The inhibitory property of the compounds was determined in terms of MIC (μg mL−1). The Co++ complexes of both the ligands showed the antimicrobial activity against all the selected strains at MIC level 31.25 μg mL−1. All compounds except for 4d and 4h showed a zone of inhibition at the MIC level 31.25 μg mL−1 against C. albicans (Table 3).

Table 3

Minimum inhibitory concentration MIC (μg mL−1) of the newly synthesized 4-hydroxy coumarin analogues and their complexes against different microbial strains against different microbial strains.

Comps.	E. colia	K. pneumoniab	S. aureusc	C. albicansd	C. neoformanse
3a	31.25	31.25	250	31.25	31.25
3b	31.25	31.25	31.25	31.25	31.25
4a	31.25	31.25	31.25	31.25	31.25
4b	31.25	31.25	31.25	31.25	250
4c	>500	250	31.25	31.25	31.25
4d	>500	500	500	500	500
4e	31.25	31.25	31.25	31.25	31.25
4f	31.25	31.25	31.25	31.25	250
4g	>500	500	250	31.25	31.25
4h	>500	>500	>500	500	>500

Escherichia coli.

Klebsiella pneumonia.

Staphylococcus aureus.

Candida albicans.

Cryptococcus neoformans.

No mortality was found for all of the test compounds per the results of the toxicity study. The synthesized compounds were safe up to 2000 mg/kg body weight. No significant change in the body weight of the animals was observed. No toxic symptoms and gross behavioural changes were observed in the animals.

Discussion

The FT/IR spectra of synthesized ligands 3a and 3b showed vibrations at 1619–1603 cm−1, 1726–1745 cm−1, 1298–1246 cm−1 and 1529–1505 cm−1 corresponding to CC str., CO str., C—O str. and NN str., respectively, which were also observed in the synthesized complexes (4a–4h). The only exception is the bands due to OH str. at 3479–3445 cm−1 exhibited in the ligands that are not observable in the complexes. In metal Cu(II), Ni(II) Co(II) and Zn(II) complexes of 3a and 3b, the FT/IR absorption band due to the hydroxyl group at 4-HC has been diminished and indicates the metal co-ordination of the OH group via deprotonation due to liberation of hydrochloric acid. In addition to these FT/IR spectral data, stretching of the M−N and M−O bonds of the complexes, which appear in the higher frequency wavenumber region in the range 451–441 and 538–531 cm−1, also indicates that complexation occurred through nitrogen and oxygen atoms from the azo-enolic ligands.22, 23 The 1H NMR spectra of ligands 3a and 3b showed the enolic OH peak at 16.81 and 16.86 ppm. The disappearance of the enolic OH group in all the complexes (4a–4h) may be due to the interaction of metal chlorides with the hydroxyl group of the ligands resulting in deprotonation and complexation of the ligands to the metal ions. Ligand 3b shows three identical, similar-environment protons at 3.83 ppm, which indicates the presence of an –OCH3 functional group. The good bathochromic shift at 463 and 450 nm exhibited by complexes 4a and 4e may be due to the attachment of transition metal ion Co++ to the respective ligands 3a and 3b. Most of the compounds showed good antimicrobial activity in comparison to ampicillin. The enhanced antimicrobial activity exhibited by complexes 4a, 4b, 4e and 4f relative to their ligands against E. coli may be due to coordination of Co++ and Ni++ ions to the respective ligands 3a and 3b. However, complexes 4a and 4e showed considerably enhanced antimicrobial activity against most of the pathogenic strains relative to their ligands. Complexation reduces the polarity of the metal ion by coordinating with ligands and increases the lipophilicity of the metals. Thus, it facilitates the penetration of the novel synthesized complexes into the lipoid cell membrane of microorganisms and inhibits their growth.

The limitations of our study include only the investigation of antimicrobial activity of the novel synthesized complexes against a few bacterial and fungal strains. Furthermore, it is necessary to investigate the antimicrobial activities of the novel complexes against multidrug-resistant microorganisms. A literature survey revealed that the metal complexes serve as vehicles for activation of the ligands as principal cytotoxic species. Therefore, these complexes may be implemented for the investigation of cytotoxic activity against different cancer cell lines.

Conclusions

In the present work, metal complexes from 3-aryl-azo-4-hydroxy coumarin analogues were synthesized. The spectral characterization of the complexes confirmed their structural environment. It is suggested that the pronounced antimicrobial activity executed by the complexes (4a and 4e) relative to their ligands permits their recommendation as a new chemical class of antimicrobial agents.

Conflict of interest

The authors have no conflict of interest to declare.

Authors' contribution

The conceptualization of this research work was designed by SKP. The experimental work, interpretation of the data and drafting of the manuscript were performed by JS. Both authors substantially contributed to fulfilling the requirements.