Synthesis and evaluation of antibacterial and antioxidative activities of carbazole derivatives

INTRODUCTION

Even though there are many antibacterial agents, multidrug resistant bacteria pose a  huge threat to public health and have become one of the biggest health problems in the last decade. Therefore, there is an urgent need to develop and provide novel and more potent antibacterial agents to overcome drug resistance [1].

Carbazole and its derivatives are an important type of nitrogen-containing aromatic heterocyclic compounds that can be found in the nature or synthesized by various methods. In nature carbazole is found as an alkaloid that is isolated from various parts of the  plant [2]. Such carbazole ring containing alkaloids are carbomycins that were first isolated from Streptoverticillium ehimense and showed a good activity against various organisms, which made carbazoles a desirable target for further biological research [3]. Carbazole and its derivatives are extensively used in various chemistry fields such as photoelectrical materials, dyes and supramolecular recognition [4–6]. Also, it is known that natural and synthesized carbazole derivatives have shown good biological activities.

It has been observed that carbazole compounds exhibit multiple mechanisms of antibacterial activity action. One is that carbazole compounds increase membrane permeability by inhibiting specific enzymatic processes. Increased penetration of free radicals violates integrity of bacterial cells [7]. Second, the mechanism of action is that carbazole compounds can interact with bacterial DNA by forming non-covalent interactions with DNA gyrase [8]. Therefore, various N and C substituted carbazoles are attractive targets to develop and produce new antibacterial agents with two possible antibacterial mechanisms of action, that could help resolve the drug resistance problem.

Even though scientific and clinical communities made a big step towards understanding how to fight with various bacterial infections, the emergence of multidrug resistant bacteria such as Escherichia coli [9], which remains a frequent cause of various urinary tract, enteric and systemic infections in humans [10], continues to present challenges to human health.

In this work, we have chosen known carbazole compounds with appropriate halogens, cyano and alkyl groups at various carbazole positions to evaluate their antibacterial activities against Gram-negative, Escherichia coli, and compare it to Gram-positive, Bacillus subtilis, as possible lead structures for further development and research of antibacterial agents; as well as to evaluate and compare the influence of different substitutes and different carbazole ring positions on antioxidant properties, seeing that there was no published information about antioxidant activities of selected compounds.

EXPERIMENTAL

Materials and methods

9H-Carbazole (I), 4,4’-dibromobiphenyl (III), 9-ethyl-9H-carbazole (5) and 1,6-dibromohexane were purchased from Sigma Aldrich.

¹H NMR (300 MHz) and ¹³C NMR (75 MHz) spectra were recorded on a Varian Unity Inova 300 apparatus.

Synthesis

3-Bromo-9H-carbazole (II). A solution of N-bromosuccinimide (NBS) (4.48 g, 23.92 mmol) in 10 mL DMF was added slowly to a solution of 9H-carbazole (I) (4 g, 0.02392 mol) in dichloromethane (75 mL) in a two-necked round bottom flask. The reaction mixture was stirred for 3  h at room temperature. The mixture was extracted with H₂O and dried over anhydrous MgSO₄ for 12 h and filtered. The excess of the solvent was evaporated and dried under vacuum. The final compound was obtained in 98% (5.76 g) as a white solid. M. p. 188–189°C. ¹H NMR (300 MHz, CDCl₃): δ 7.25 (m, 1H), 7.31 (d, J = 8.4 Hz, 1H), 7.43 (m, 1H), 7.5 (d, J = 6.6 Hz, 1H), 8.0 (d, J = 7.8 Hz, 1H), 8.08 (s, 1H), 8.1 (s, 1H), 8.18 (d, J = 4 Hz, 1H). ¹³C NMR (75 MHz, CDCl₃): δ 139.9, 138.1, 128.6, 126.7, 125.2, 123.4, 122.5, 120.6, 120.0, 112.3, 112.1, 110.9.

3-Cyano-9H-carbazole (1a) [11]. A solution of 3-bromo-9H-carbazole (II) (23.08 g, 94 mmol) and cuprous cyanide (9.33  g, 0.103  mol) in N-methyl-pyrrolidone (300 ml) was heated at 200°C for 5 h. The cooled reaction mixture was poured on to water (600 ml) and the precipitate was filtered off and washed with ethyl acetate (3 × 50 ml). The filtrate was extracted with ethyl acetate (3 × 250 ml) and the  combined ethyl acetate extracts were washed with water (150 ml) and brine (150 ml), dried using MgSO₄ and concentrated in vacuum. The  residue was crystallized from heptane and recrystallized from acetonitrile (70  ml) acquiring 7.16  g, 40% of 1a as a white solid. M. p. 180–181°C. ¹H NMR (300 MHz, DMSO) δ 11.91 (s, 1H), 8.85 (s, 1H), 8.27 (d, J = 7.8 Hz, 1H), 7.78 (dd, J = 8.4, 1.6 Hz, 1H), 7.67 (d, J = 8.4 Hz, 1H), 7.61 (d, J = 8.0 Hz, 1H), 7.56 (t, J = 7.2 Hz, 1H), 7.33 (t, J = 8.0 Hz, 1H). ¹³CNMR (75 MHz, DMSO): δ 142.6, 141.2, 129.5, 127.9, 126.5, 123.6, 122.5, 121.9, 121.5, 120.8, 113.0, 112.5, 101.1.

4,4’-Dibromo-2-nitrobiphenyl (IV). 4,4’-Dibromobiphenyl (III) (10 g, 32 mmol) was dissolved in glacial acetic acid (120 mL), and the mixture was stirred and heated to 100°C for 24 h. Then, fuming concentrated nitric acid (95%, 40 mL) was added and the resulting mixture was allowed to react for another 30 min. After the reaction, the solution was cooled to room temperature, the  crude product was filtered. After recrystallization from ethanol, the  title compound was obtained in 91% yield as white crystals. ¹H  NMR (300  MHz, CDCl₃): δ 8.03 (d, J = 1.8 Hz, 1H), 7.76 (dd, J₁ = 8.1 Hz, J₂ = 1.8 Hz, 1H), 7.54–7.59 (m, 2H), 7.31 (s, 1H), 7.14–7.18 (m, 2H).

2,7-Dibromo-9H-carbazole (V). 7.8 g (22 mmol) of 4,4’-dibromo-2-nitrobiphenyl (IV) was dissolved in phosphorous acid triethyl ester (30  mL) and the mixture was heated to 150°C under the protection of argon. The system was allowed to react for 24 h and a brown solution was obtained. The volatile solvents were then removed by vacuum distillation. The  solution left was purified by column chromatography with ethyl acetate/petroleum ether (10:1, v/v) as the eluent. Finally, a white solid was obtained for 2,7-dibromocarbazole (V) in 48% yield. ¹H NMR (300 MHz, acetone-d₆): δ 10.64 (s, 1H), 8.09 (d, J = 8.4 Hz, 2H), 7.75 (d, J = 1.8 Hz, 2H), 7.37 (dd, J = 8.4, 1.8 Hz, 2H).

2,7-Dicyano-9H-carbazole (1b) [12]. Copper(I) cyanide (CuCN) (14.7 g, 164.3 mmol) was added to a stirred solution of 2,7-dibromo-9H-carbazole (IV) (12.28 g, 37.75 mmol) in DMF (150 mL). The solution was maintained at reflux under nitrogen for 9 h. In the reaction mixture 40 mL of ethylenediamine and 20 g of CuCN were used to give a white powder (7.92 g, 96.6%). M. p. 279–281°C. ¹H NMR (300  MHz, acetone-d₆): δ 11.3 (br, 1H), 8.46–8.43 (d, 2H), 8.06 (s, 2H), 7.62–7.59 (d, 2H). ¹³C NMR (75 MHz, acetone-d₆): δ 141.0, 126.1, 123.4, 123.1, 120.1, 116.8, 110.7.

3-Iodo-9H-carbazole (2a) [13]. 9H-carbazole (I) (16.7 g, 101 mmol) was dissolved in boiling glacial acetic acid (250 mL) and KI (11.73 g, 135 mmol) was added. The solution was cooled, ground potassium iodate (23.42 g, 150 mmol) was added, and the  mixture was boiled until it acquired a  clear straw-coloured tint (10 min). The hot solution was decanted from the  undissolved potassium iodate, and it was cooled to 45°C. The faintly brown plates were rapidly filtered off and recrystallized from alcohol, and the solution was allowed to cool to 45°C. The  faintly brown plates were rapidly filtered off and recrystallized from ethanol; the  solution was allowed to cool to 45°C and filtered, yielding 9.73 g, 47% of 2a as a brown solid. M. p. 202°C. ¹H NMR (300  MHz, CDCl₃): δ 8.41 (s, 1H), 8.11 (s, 1H), 8.04 (d, J = 1.7 Hz, 1H), 7.68 (dd, J = 1.7 Hz, 1H), 7.42–7.49 (m, 2H), 7.22–7.28 (m, 2H). ¹³C  NMR (75  MHz, CDCl₃): δ 139.5, 138.6, 134.1, 129.2, 126.6, 125.9, 122.1, 120.5, 119.9, 112.6, 110.7.

3,6-Diiodo-9H-carbazole (2b) [13]. To a solution of 9H-carbazole (I) (5.00  g, 30.43  mmol) in acetic acid (85  mL) potassium iodide (6.67  g, 40.17  mmol) was added. With stirring, potassium iodate (9.77 g, 45.65 mmol) was slowly added into the mixture and refluxed for 10 min. The reaction mixture was cooled to room temperature, filtered and washed with acetic acid (50 mL) to yield in 96% (11.94 g) as pale-yellow powder. M. p. 208–211°C. ¹H NMR (300 MHz, CDCl₃): δ 8.30 (d, J = 1.6 Hz, 2H), 8.07 (s, 1H), 7.67 (d, J = 8.8 Hz, 1.6 Hz, 2H), 7.20 (d, J = 8.4 Hz, 2H). ¹³C NMR (75 MHz, CDCl₃): δ 138.4, 134.7, 129.2, 123.4, 112.6, 82.4.

1,3,6-Tribromo-9H-carbazole (3) [14]. To a stirred solution of 9H-carbazole (I) (1 mmol) in dichloromethane (50 mL), containing silica (10 g), a  solution of NBS (0.890  g, 5.0  mmol) in dichloromethane (75  mL) was added dropwise. The  reaction mixture was stirred for appropriate time in the  absence of light at ambient temperature until TLC indicated that it was complete. The  reaction mixture was then filtered, and the silica washed with dichloromethane (3  ×  15  mL). The  combined extracts were washed with water (100 mL) and the organic layer was dried and evaporated to yield 3 as a  white solid in 96%. M.  p. 172–173°C. ¹H  NMR (300 MHz, acetone-d₆): δ 7.50 (d, J = 8.0 Hz, 1H), 7.54 (d, J = 8.0 Hz, lH), 7.67 (s, 1H); 8.26 (s, 2H); 10.70 (s, 1H). ¹³C NMR (75  MHz, acetone-d₆): δ 105.19, 112.1, 113.1, 114.2, 123.3, 124.4, 124.8, 125.5, 130.5, 131.1, 138.5, 139.8.

1,6-Di(3-iodo-9H-carbazolyl)hexane (4) [15]. A mixture containing (12 g, 41 mmol) of 3-iodo-9H-carbazole (2a), (3.9 g, 16 mmol) of 1,6-dibromohexane, and (0.4 g, 1.2 mmol) of KOH were heated to reflux in 70 mL of acetone, and then (1.8 g, 32 mmol) of powdered potassium hydroxide was added. After refluxing for 12 h, during which time a white precipitate formed, acetone was removed, and the reaction product was dissolved in chloroform. The obtained suspension was filtered, and the solution was washed with water. After removal of the solvent, the product was purified by two crystallizations from acetone to yield 4.7  g, 44% of white crystals. ¹H  NMR (300 MHz, CDCl₃): δ 1.24–1.31 (m, 4H), 1.67–1.82 (m, 4H), 4.15 (t, J = 6.9 Hz, 4H), 7.04 (d, J = 8.8 Hz, 2H), 7.16–7.64 (m, 8H), 7.99 (d, J = 7.8 Hz, 2H), 8.35 (s, 2H).

Evaluation of antibacterial activity

Antibacterial activity of the compounds was tested using the disk diffusion method [16]. In this study inhibition of bacterial growth was investigated against Gram-positive bacteria Bacillus subtilis and Gram-negative bacteria Escherichia coli. The  solution (1 mg/ml) of the compounds was prepared in DMSO and then diluted to various concentrations (31.25–1000  μg/ml) in DMSO. Bacterial cultures were cultivated in Petri dishes at 37°C for 24 h on the Luria-Bertani (LB) agar medium [17]. 50 μL inoculum containing bacterial cells were spread across the LB agar medium. Sterile filter paper disks were soaked in 25  μL of each compound solution, and then the  disks were put on the  LB agar medium. Amoxicillin and ciprofloxacin were used as positive control, and DMSO was used as the negative control. Petri dishes were incubated aerobically at 37°C and examined for zones of inhibition after 24 h. The inhibition zones were measured using a ruler (Fig. 1).

1,1-Diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay

The free radical scavenging activity of the  compounds was measured by the DPPH method [18]. At first, a solution (5 mM) of the compounds was prepared in DMSO. Then, a  1  mM solution of DPPH in ethanol was prepared and 1 mL of this solution was added to the solutions of the selected compounds. The mixture was vigorously stirred and allowed to stand at room temperature. After 20 min, the absorbance of the reaction mixture was measured at 517 nm with a UV-1280 spectrophotometer (Shmidazu). The activity of DPPH radical scavenging was calculated according to the following equation:

Here A_b is the absorbance of the control reaction, and A_a is the absorbance in the presence of the compounds. Each experiment was repeated three times.

Ferric reducing antioxidant power assay (FRAP)

Reducing properties were investigated using the FRAP method, which is based on the reduction of a ferric-tripyridyl triazine complex to its ferrous coloured form in the presence of antioxidants [19]. The FRAP reagent contained 2.5 mL of a 10 mM TPTZ (2,4,6-tripyridyl-s-triazine) solution in 40 mM HCl, also 2.5 ml of FeCl₃ (20 mM) and 25 ml of acetate buffer (0.3 M, pH = 3.6). 100 μL of the  tested compounds (5 mM) were mixed with 3 mL of the FRAP reagent. Afterwards, the reaction mixture was incubated at 37°C. After 24 h, the absorbance of the reaction mixture at 593 nm was measured spectrophotometrically. For comprising of the calibration curve, five concentrations of FeSO₄∙7H₂O (5, 10, 15, 20, 25 μM) were used and the absorbances were measured as a sample solution [20]. Each experiment was repeated three times.

RESULTS AND DISCUSSION

A series of carbazole-based derivatives have been designed and synthesized (Scheme, Table 1), and their antibacterial activity was evaluated against Bacillus subtilis and Escherichia coli. Various functional groups were introduced into carbazole-based compounds in order to investigate their biological activity.

Under the standard reaction conditions, when the mixture of II, CuCN in NMP was stirred in air at 155°C for 22 h, 3-cyano-9H-carbazole (1a) was isolated in 30% yield. The reaction of dibromide V with CuCN in DMF gave 2,7-dicyano-9H-carbazole (1b) within 9 h. Other materials 3-iodo-9H-carbazole (2a) and 3,6-diiodo-9H-carbazole (2b) were synthesized from commercially available 9H-carbazole (I) by Tucker iodination with KI/KIO₃ in acetic acid. Production of 1,3,6-tribromo-9H-carbazole (3) provided a simple and clean synthesis of 9H-carbazole (I) by use of three equivalents of NBS/silica. 9,9’-(Hexane-1,6-diyl)bis(3-iodo-9H-carbazole) (4) was synthesized by the alkylation reaction with an excess amount of 1,6-dibromohexane in acetone. All derivatives (1a, 1b, 2a, 2b, 3 and 4) were characterized by using ¹H NMR, ¹³C NMR spectroscopies and mass spectrometry.

Compounds 1a–5 were evaluated for their antibacterial activity against the strains of Bacillus subtilis and Escherchia coli by the disk diffusion method. The antibacterial activity of the tested compounds was compared with the activity of the known antibiotics – amoxicillin, 62.50 μg/ml (171.1 μM) and ciprofloxacin, 3.90 μg/ml (11.8 μM).

Carbazole-based compounds 1a, 2a and 2b were the most active against Gram-positive Bacillus subtilis, they showed inhibitory activity at 31.25 μg/ml (162.6, 106.6, 74.6 μM) (Table 2). These compounds showed a greater activity than that of amoxicillin, which was active only at 62.5 μg/ml (171.1 μM). Brominated carbazole compound 3 was slightly less active, 62.5 μg/ml (154.8 μM), but still comparable to amoxicillin. Against Gram-negative Escherichia coli strains the  selected compounds were slightly less active, but still showed good results. Three -Br groups containing carbazole compound 3 were the most active at 31.25 μg/ml (77.4 μM), it showed a greater activity than that of amoxicillin 62.5 μg/ml (171.1 μM). Compounds 2a and 2b were not as active as against Bacillus subtilis, but still comparable to amoxicillin and showed activity at 62.5 μg/ml (213.2, 149.2 μM). Ciprofloxacin suppressed the growth of tested bacteria at 3.9 μg/ml (11.8 μM).

Table 1. Structures of the carbazolyl fragment containing compounds 1a–5

Abbreviation	Name	Structure
1a	3-Cyano-9H-carbazole
1b	2,7-Dicyano-9H-carbazole
2a	3-Iodo-9H-carbazole
2b	3,6-Diiodo-9H-carbazole
3	1,3,6-Tribromo-9H-carbazole
4	9,9’-(Hexane-1,6-diyl)bis(3-iodo-9H-carbazole)
5	9-Ethyl-9H-carbazole

Evaluation of the antibacterial activity revealed that -Br, -CN and -I groups introduced into various carbazole ring positions determined its antibacterial activity. We can see that -Br carbazole compound 3 had a greater activity against Gram-negative, Escherichia coli, and -I groups containing carbazole compounds 2a and 2b showed better results against Gram-positive, Bacillus subtilis, strains. Interestingly, compound 1a containing only one -CN group at the C-3 position showed a significant inhibitory activity against both tested bacteria, whereas compound 1b containing two -CN groups at C-2 and C-7 positions, showed a  very weak activity. This suggests that the  substitutes introduced into C-3 and C-6 positions have a greater influence on antibacterial properties than the substitutes introduced into C-2 and C-7 positions. This tendency has also been observed among isopropanol-conjugated carbazole azole derivatives [6]. They noted that the -Br substitute at the carbazole C-3 position had a greater antibacterial activity than that of the -Br substitute at the C-2 position containing carbazole [6].

DMSO for negative control, NA for no inhibitory activity.

It should also be noted that compound 4 containing two 3-iodo-9H-carbazolyl fragments showed a weaker activity than that of compound 2a, made of only a  3-iodo-9H-carbazolyl fragment. Also, compound 5, consisting of an ethyl group at the C-9 position, did not show any antibacterial activity against the tested bacteria. This could suggest that introducing alkyl or other closed form structures has a negative effect on antibacterial properties.

Antioxidant activities of compounds 1a–5 were evaluated using the (1,1-diphenyl-2-picrylhy-drazyl) (DPPH) radical scavenging method (Fig. 2) and the ferric reducing antioxidant power (FRAP) assay (Fig. 3).

The DPPH assay method is based on the reduction of DPPH. When a  free radical DPPH meets with a hydrogen donor, it is reduced to the DPPHH therefore the free radical DPPH which has purple colour is decolourized to yellow. Measuring this change absorption at 517 nm allows the  calculations of antioxidant activity [21].

As seen from the  results presented in Fig. 2, 5 out of 7 compounds showed weak to moderate DPPH radical scavenging properties. The best antioxidative activity was shown by ascorbic acid (797.57 μM), which was used as standard. Standard moderate radical scavenging abilities were shown by compounds 2a (365.64 μM) and 2b (348.02 μM), containing one and two -I atoms at C3 and C6 carbazole positions. Two -CN groups containing compound 1b showed two times weaker activity, at 163.00 μM, whereas compound 1a with only one -CN group showed no radical scavenging activity at the  tested concentration. Compound 5, with an introduced ethyl substitute at the  C9 position, and two 3-iodo-9H-carbazolyl fragments containing compound 4 showed weak radical scavenging abilities, 9.53 μM and 54.33 μM, respectively. Compound 3, containing three -Br atoms, showed no antioxidative activity.

The radical scavenging activities of compounds 1a–5 may be attributed to the electronic effects of substituent groups on the carbazole scaffold and the free -NH group at the C9 carbazole position. The importance of the free -NH group can be seen between compound 2a, containing one –I atom at the C3 position, which showed the best radical scavenging ability, and compound 4, containing two 3-iodo-9H-carbazolyl fragments and no free -NH group, which showed a  lot weaker radical scavenging activity.

The FRAP method is based on electron transfer rather than hydrogen atom transfer [17]. The method is based on the ability of an antioxidant to reduce the Fe³⁺ complex with 2,4,6-trypyridyl-s-triazine (Fe(TPTZ)³⁺) to the  Fe²⁺ complex (Fe(TPTZ)²⁺) [22]. The increase in absorbance of the intensely blue coloured Fe²⁺ complex is measured at 593 nm and results can be expressed as Fe²⁺ concentration (μM).

The results, shown in Fig. 3, revealed that compared to ascorbic acid (115.67 μM), which was used as standard, all tested compounds showed a weak activity to reduce Fe(TPTZ)³⁺ to Fe(TPTZ)²⁺. Out of the tested compounds, compound 2a, containing one -I atom, at the C3 carbazole ring position, showed a notably higher ability (16.60 μM) to reduce Fe(TPTZ)³⁺. Compounds 1b, 2b, 3, 4 and 5 showed similar results (4.80–9.02 μM). Lastly, only at 1.05 μM, compound 1a showed the weakest antioxidant activity according to the FRAP assay.

Even though the literature review revealed that good reductive properties were shown by carbazoles containing -OH [23], -NO₂ and OCH₃ [24], the ability to reduce Fe(TPTZ)³⁺ to Fe(TPTZ)²⁺ of the tested compounds 1a–5 can also be related to the  electronic effects of substituent groups and the redox properties of these compounds.

CONCLUSIONS

In summary, various mono-, di- and tri-substituted carbazole derivatives, containing appropriate halogens, cyano and alkyl groups, were synthesized. Screening of their antibacterial activity has displayed that against Bacillus subtilis the  most active antibacterial agents were 3-cyano-9H-carbazole, 3-iodo-9H-carbazole and 3,6-diiodo-9H-carbazole, they suppressed the growth of bacteria at a  concentration of 31.25 μg/ml (162.6, 106.6, 74.6 μM). Escherichia coli bacteria were the most sensitive to 1,3,6-tribromo-9H-carbazole, which inhibited their growth at a  concentration of 31.25 μg/ml (77.4 μM). The antibacterial activity assay also revealed that the carbazole derivatives substituted at C-3 and C-6 positions displayed better antibacterial activities than the carbazoles substituted at C-2 and C-7 positions. Also, it should be noted that the carbazoles containing -I substitutes better suppressed the growth of Gram-positive bacteria and the -Br containing carbazole better inhibited the growth of Gram-negative bacteria. The antioxidant activity assay revealed that the tested compounds displayed weak to moderate radical scavenging properties according to the 1,1-diphenyl-2-picryl-hydrazyl method and weak reductive properties according to the ferric reducing antioxidant power method, resulting in that CN, -Br and -I substitutes introduced into carbazole did not determine good radical scavenging and reducing properties.

ACKNOWLEDGEMENTS

This research was supported by the Research, Development and Innovation Fund of Kaunas University of Technology and the Research Fund of Lithuanian University of Health Sciences/The Research, Development and Innovation Fund of Vytautas Magnus University (SLOPSINT). We are grateful to Dr. Eigirdas Skuodis and Dr. Gintarė Krucaitė for the provided compounds.

Received 19 November 2019

Accepted 10 December 2020

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Kęstutis Dabrovolskas, Ilona Jonuškienė, Simona Sutkuvienė, Dalius Gudeika

KARBAZOLO DARINIŲ SINTEZĖ BEI JŲ ANTIBAKTERINIŲ IR ANTIOKSIDACINIŲ SAVYBIŲ VERTINIMAS

Santrauka
Pagal žinomus metodus buvo susintetinti septyni junginiai ir, taikant diskelių difuzijos metodą, ištirtos jų antibakterinės savybės dviems bakterijoms (Bacillus subtilis ir Escherichia coli). Antioksidacinės savybės buvo nustatytos remiantis laisvųjų 1,1-difenil-2-pikrilhidrazilo radikalų sugaudymo ir geležies jonų redukcijos antioksidacinio aktyvumo nustatymo metodais. Diskelių difuzijos metodu buvo nustatyta, kad šeši iš septynių junginių turėjo antibakterinį poveikį tirtoms bakterijoms ir jų augimą slopino esant įvairioms junginių koncentracijoms – nuo 31,25 iki 250 μg/ml. Bacillus subtilis bakterijas stipriau veikė 3-ciano-9H-karbazolas, 3-jod-9H-karbazolas ir 3,6-dijod-9H-karbazolas, o Echerichia coli bakterijas  –  1,3,6-tribrom-9H-karbazolas, palyginti su amoksicilinu. Tirti junginiai pasižymėjo silpnomis vidutinėmis radikalų sugaudymo savybėmis, kai buvo taikytas 1-difenil-2-pikrilhidrazilo laisvųjų radikalų sugaudymo metodas, ir silpnomis redukcinėmis savybėmis taikant geležies jonų redukcijos antioksidacinio aktyvumo nustatymo metodą.