5-Bromo-1-(4-chlorobenzyl)-1H-indole-2-carboxamides as new potent antibacterial agents

Yogesh D. Mane; Smita S. Patil; Dhanraj O. Biradar; Bhimrao C. Khade

doi:10.1515/hc-2018-0107

Article Open Access

5-Bromo-1-(4-chlorobenzyl)-1H-indole-2-carboxamides as new potent antibacterial agents

Yogesh D. Mane , Smita S. Patil , Dhanraj O. Biradar and Bhimrao C. Khade

Published/Copyright: November 13, 2018

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From the journal Heterocyclic Communications Volume 24 Issue 6

Abstract

Ten 5-bromoindole-2-carboxamides were synthesized, characterized and evaluated for antibacterial activity against pathogenic Gram-negative bacteria Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa and Salmonella Typhi using gentamicin and ciprofloxacin as internal standards. Compounds 7a–c, 7g and 7h exhibit high antibacterial activity with a minimum inhibitory concentration (MIC) of 0.35–1.25 μg/mL. Compounds 7a–c exhibit antibacterial activities that are higher than those of the standards against E. coli and P. aeruginosa.

Keywords: antibacterial activity; indole; indole-2- carboxamide

Introduction

The treatment of bacterial infections is a challenging therapeutic problem because of the increasing resistance of disease-causing bacteria against existing antibacterial agents [1], [2]. Infections with Gram-negative bacteria are especially worrisome [3]. Considering the magnitude of ever-growing antibacterial resistance, it is necessary to discover novel chemical entities with improved pharmacological profiles. Natural and synthetic heterocycles containing an indole moiety [4] are known for their significant biological activities [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22]. Compounds with an indole-2-carboxamide scaffold (Figure 1) are of special interest (Figure 1). In this paper, we report the synthesis and antibacterial activities of indole-2-carboxamides 7a–j (Scheme 1).

Figure 1

Reported bioactive indole-2-carboxamides.

Scheme 1

Synthesis of indole-2-carboxamides: (a) (i) NaNO₂, HCl, 0°C, 15 min; (ii) SnCl₂, HCl, 0°C, 4 h; (b) ethyl pyruvate, EtOH, argon, reflux 5.5 h; (c) polyphosphoric acid (PPA), 120°C, 20–30 min; (d) 4-chlorobenzyl chloride, Cs₂CO₃, DMF, 60°C, 16 h; (e) LiOH, THF, H₂O, EtOH, stirring, room temperature (rt), 3–4 h; (f) amine, EDC·HCl, HOBt, DIPEA, DMF, 0°C to rt, 20–30 h.

Results and discussion

As can be seen from Scheme 1, the intermediate product 6 was prepared starting with commercially available 4-bromoaniline (1). Diazotization of 1 followed by reduction afforded 4-bromophenylhydrazine (2) [23]. Condensation of 2 with ethyl pyruvate followed by cyclization of the resultant product 3 furnished ethyl 5-bromo-1H-indole-2-carboxylate (4) [23]. Benzylation of 4 with 4-chlorobenzyl chloride gave N-benzylated ester 5, the hydrolysis of which furnished the desired carboxylic acid 6. Coupling of the carboxylic acid 6 with appropriate amines using 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC.HCl), hydroxybenzotriazole (HOBt) and N,N-diisopropylethylamine (DIPEA)/ triethylamine (TEA) in dimethylformamide (DMF) afforded the target carboxamides 7a–j in good to excellent yields.

Compounds 7a–j were evaluated for their in vitro antibacterial activity against pathogenic Gram-negative bacteria Klebsiella pneumoniae (ATCC 27736), Escherichia coli (ATCC 9637), Pseudomonas aeruginosa (ATCC BAA427) and Salmonella enterica serovar Typhi (ATCC 19430) [24]. The experiments were conducted using the broth microdilution technique described by Clinical and Laboratory Standards Institute (CLSI), 2012 (formerly NCCLS) [24]. The activities were compared with those of antibacterial drugs gentamicin and ciprofloxacin. The results are reported in Table 1.

Table 1

In vitro antibacterial activity of compounds 7a–j against pathogenic bacteria.

Compound	MIC (μg/mL)
Compound	K. pneumoniaATCC 27736	E. coliATCC 9637	P. aeruginosaATCC BAA427	S. Typhi ATCC 19430
7a	12.25	0.35	3.25	>50
7b	12.5	0.39	6.25	>50
7c	1.25	1.05	0.15	1.05
7d	12.5	12.25	12.25	>50
7e	12.25	12.5	6.35	>50
7f	>50	>50	>50	>50
7g	25.0	12.25	0.15	>50
7h	12.25	6.25	0.65	>50
7i	>50	7.39	6.25	>50
7j	30.6	8.42	20.7	>50
Gentamicin	0.25	1.25	3.02	1.65
Ciprofloxacin	0.5	1.05	1.25	3.01

Among the tested compounds, carboxamides 7a–c, 7g and 7h show good antibacterial activity against E. coli and P. aeruginosa with a minimum inhibitory concentration (MIC) of 0.15–3.25 μg/mL. When compared with the commercial references (gentamicin and ciprofloxacin) as positive controls, the activity of 7c is identical with that of ciprofloxacin and, more significantly, better than the activity of gentamicin against E. coli. Compounds 7a and 7b show a 2.5- to 3-fold greater effect than both standards against E. coli. Compound 7c exhibits excellent activity against Salmonella Typhi and is 1.6 and 3-fold more active than gentamicin and ciprofloxacin, respectively.

Conclusions

New 1-benzyl-5-bromoindole-2-carboxamides 7a–j were synthesized and screened in vitro for antibacterial activity. Many compounds show moderate to excellent antibacterial activity compared to the reference drugs. Compounds 7a,b show higher antibacterial activity than standard drugs against E. coli while compounds 7c, 7g and 7h are more active against P. aeruginosa than the standard drugs.

Experimental

Reagents and solvents were purchased from commercial sources and used without further purification. Melting points were determined in open capillary tubes and are uncorrected. Synthesis of compounds was monitored by thin-layer chromatography (TLC) on silica gel-G plates of 0.5-mm thickness and spots were visualized by treatment with iodine and UV light. All compounds were purified by crystallization. Mass spectra were recorded on the Shimadzu GC-MS-QP-2010 model using the direct inlet probe technique. The ¹H NMR (400 MHz) and ¹³C NMR (100 MHz) spectra were recorded in dimethyl sulfoxide-d₆ (DMSO-d₆) solutions on a Bruker spectrometer.

4-Bromophenylhydrazine (2)

This compound was obtained by using a previously published procedure [23]; yield 82% of orange crystals; ¹H NMR: δ 7.2 (d, J=8.8 Hz, 2H), 6.9 (s, 1H), 6.7 (d, J=8.8 Hz, 2H), 4.4 (s, 2H); ¹³C NMR: δ 113.4, 117.2, 133.6, 134.3.

Ethyl pyruvate 4-bromophenylhydrazone (3)

A mixture of compound 2 (5.0 g, 26.7 mmol) and ethyl pyruvate (3.7 g, 32.1 mmol) in EtOH (30 mL) was heated under reflux under argon for 5 h. After cooling, the resultant precipitate was filtered and washed with water. The crude product was triturated with cyclohexane and filtered to give a yellow solid 3 [23]; yield 76% of yellow crystals; ¹H NMR: δ 9.9 (s, 1H), 7.4 (d, J=8.8 Hz, 2H), 7.2 (d, J=8.8 Hz, 2H), 4.2 (q, J=7.2 Hz, 2H), 2.1 (s, 3H), 1.3 (t, J=7.2 Hz, 3H); ¹³C NMR: δ 12.4, 14.7, 60.8, 112.6, 116.1, 132.2, 133.3, 144.2, 165.3.

Ethyl 5-bromo-1H-indole-2-carboxylate (4)

A mixture of ethyl pyruvate 4-bromophenylhydrazone 3 (5.0 g, 17.5 mmol) and polyphosphoric acid (44 g) was heated to 120°C for 0.5 h. The mixture was then cooled, poured into ice-cold water and neutralized with saturated aqueous sodium bicarbonate. The product was extracted with EtOAc and the extract was dried over Na₂SO₄, filtered and concentrated under reduced pressure to give 4 [23]; yield 82% of pale-yellow crystals; ¹H NMR: δ 12.0 (s, 1H), 7.8 (d, J=0.8 Hz, 1H), 7.4 (dd, J=8.8 Hz and 0.8 Hz, 1H), 7.3 (dd, J=8.8 Hz and 1.2 Hz, 1H), 7.1 (d, J=1.2 Hz, 1H), 4.3 (q, J=7.2 Hz, 2H), 1.3 (t, J=7.2 Hz, 3H); ¹³C NMR: δ 13.8, 61.2, 109.1, 113.8, 114.1, 121.8, 124.9, 126.1, 133.4, 135.6, 162.3.

Ethyl 1-(4-chlorobenzyl)-5-bromo-1H-indole-2-carboxylate (5)

4-Chlorobenzyl chloride (2.1 mL, 13.0 mmol) was added to a suspension of cesium carbonate (4.25 g, 13.0 mmol) and ethyl 5-bromo-1H-indole-2-carboxylate (4, 3.5 g. 13.0 mmol) in DMF (35 mL). The mixture was stirred at 60°C for 6 h (monitored by TLC), poured into water (25 mL) and extracted with EtOAc (3×20 mL). The extract was washed with a saturated solution of NaHCO₃ (20 mL), water (10 mL), brine (10 mL), dried over anhydrous Na₂SO₄ and concentrated under reduced pressure. The residue was subjected to silica gel chromatography eluting with hexanes/EtOAc (90:10) to afford 4.5 g (88%) of compound 5 as a white solid; yield 88%; ¹H NMR: δ 7.8 (d, J=1.5 Hz, 1H), 7.6 (d, J=8.1 Hz, 2H), 7.5 (dd, J=8.5 Hz and 1.5 Hz, 1H), 7.4 (d, J=8.5 Hz, 1H), 7.3 (d, J=8.1 Hz, 2H), 7.1 (s, 1H), 5.8 (s, 2H), 4.3 (q, 2H), 1.3 (t, 3H); ¹³C NMR: δ 14.5, 47.2, 61.2, 110.5, 113.8, 125.1, 127.7, 128.2, 128.5, 128.7, 128.9, 132.2, 137.6, 138.0, 161.3.

1-(4-Chlorobenzyl)-5-bromo-1H-indole-2-carboxylic acid (6)

A solution of ethyl 1-(4-chlorobenzyl)-5-bromo-1H-indole-2-carboxylate (5, 3.0 g, 7.6 mmol) in tetrahydrofuran (THF) (24 mL) was treated dropwise with a solution of lithium hydroxide monohydrate (0.63 g, 11.5 mmol) in water (6 mL). The mixture was stirred at room temperature for 16 h and then acidified to pH 2–3 with 1N HCl. The mixture was extracted with EtOAc (3×30 mL). The extract was dried over anhydrous Na₂SO₄ and then concentrated under reduced pressure. The product 6 was isolated by silica gel chromatography eluting with hexanes/EtOAc (50:50); yield 2.61 g (94%) of a white solid; ¹H NMR: δ 11.2 (s, 1H), 7.9 (d, J=1.5 Hz, 1H), 7.6 (d, J=8.1 Hz, 2H), 7.5 (dd, J=8.5 Hz and 1.5 Hz, 1H), 7.4 (d, J=8.5 Hz, 1H), 7.3 (d, J=8.1 Hz, 2H), 7.1 (s, 1H), 5.8 (s, 2H); ¹³C NMR: δ 46.9, 110.3, 113.6, 113.7, 125.0, 127.7, 127.9, 128.5, 128.9, 129.7, 132.1, 137.7, 137.9, 162.9.

General procedure for synthesis of 1-(4-chlorobenzyl)-5-bromo-1H-indole-2-carboxamides 7a–j

A solution of 1-(4-chlorobenzyl)-5-bromo-1H-indole-2-carboxylic acid (6, 250 mg, 0.68 mmol) in DMF/CH₂Cl₂ (10 mL) was cooled to 0°C and treated with EDC·HCl (261 mg, 1.36 mmol), HOBt (110 mg, 0.82 mmol) and DIPEA/TEA (12 μL, 1.36 mmol). The mixture was stirred for 30 min, treated with an amine (0.82 mmol) and stirred for an additional 20–30 h at room temperature. After completion of the reaction (monitored by TLC), the mixture was diluted with dichloromethane (20 mL) and washed with saturated solution of NH₄Cl (20 mL), water (20 mL) and brine (20 mL). The organic layer was dried over anhydrous Na₂SO₄ and concentrated under reduced pressure. The product 7a–j was isolated by flash chromatography on silica gel eluting with hexanes/EtOAc (95:5).

5-Bromo-1-(4-chlorobenzyl)-N-(4-methoxybenzyl)-1H-indole-2-carboxamide (7a)

Yield 82% of white crystals; mp 270–272°C; ¹H NMR: δ 9.1 (t, J=4.0 Hz, 1H), 7.9 (s, 1H), 7.5 (d, J=8.0 Hz, 1H), 7.4 (d, J=8.0, 1H), 7.3 (d, J=8.1 Hz, 2H), 7.2 (s, 1H), 7.1 (d, J=8.1 Hz, 2H), 7.0 (d, J=8.0 Hz, 2H), 6.8 (d, J=8.0 Hz, 2H), 5.8 (s, 2H), 4.3 (d, J=4.0 Hz, 2H), 3.7 (s, 3H); ¹³C NMR: δ 41.6, 46.4, 55.1, 104.8, 113.0, 113.7, 124.0, 126.4, 127.7, 128.5, 131.3, 131.7, 132.9, 136.7, 137.5, 158.2, 161.3; MS (ESI): m/e 482 (M)⁺, 484 (M+2)⁺, 486 (M+4)⁺. Anal. Calcd for C₂₄H₂₀BrClN₂O₂: C, 59.58; H, 4.17; N, 5.79. Found: C, 59.51; H, 4.09; N, 5.73.

5-Bromo-1-(4-chlorobenzyl)-N-(4-iodobenzyl)-1H-indole-2-carboxamide (7b)

Yield 78% of white crystals; mp 284–286°C; ¹H NMR: δ 9.1 (t, J=5.8 Hz, 1H), 7.7 (s, 1H), 7.5 (d, 1H), 7.4 (d, 1H), 7.3 (d, 2H), 7.1 (m, 3H), 6.9 (d, J=8.2 Hz, 2H), 6.7 (d, J=8.2 Hz, 2H), 5.7 (s, 2H), 4.3 (d, J=5.8 Hz, 2H); ¹³C NMR: δ 45.4, 50.0, 92.0, 108.6, 116.7, 117.4, 127.7, 130.1, 131.4, 132.2, 135.0, 135.4, 136.7, 140.4, 141.3, 161.9; MS (ESI): m/e 578 (M)⁺, 580 (M+2)⁺, 582 (M+4)⁺. Anal. Calcd for C₂₃H₁₇BrClIN₂O: C, 47.66; H, 2.96; N, 4.83. Found: C, 47.61; H, 2.89; N, 4.77.

5-Bromo-1-(4-chlorobenzyl)-N-(1-(2-methoxyphenyl)propan-2-yl)-N-methyl-1H-indole-2-carboxamide (7c)

Yield 76% of white crystals; mp 291–293°C; ¹H NMR: δ 8.0 (d, J=1.4 Hz, 1H), 7.6 (d, J=8.1 Hz, 1H), 7.5 (dd, J=8.1 Hz and 1.4 Hz, 1H), 7.4 (d, J=8.5 Hz, 2H), 7.3 (s, 1H), 7.2 (d, J=8.5 Hz, 2H), 6.9–7.1 (m, 4H), 5.8 (s, 2H), 4.2 (m, 1H), 3.8 (s, 3H), 3.4 (s, 3H), 2.9 (dd, 1H), 2.6 (dd, 1H), 1.2 (d, 3H); ¹³C NMR: δ 18.4, 32.7, 33.4, 49.5, 55.70, 56.7, 104.5, 112.3, 113.4, 123.9, 126.5, 127.1, 127.8, 127.9, 128.7, 130.7, 131.5, 132.8, 135.7, 137.6, 161.0; MS (ESI): m/e 524 (M)⁺, 526 (M+2)⁺, 528 (M+4)⁺. Anal. Calcd for C₂₇H₂₆BrClN₂O₂: C, 61.67; H, 4.98; N, 5.33. Found: C, 61.59; H, 4.94; N, 5.28.

1′-(5-Bromo-1-(4-chlorobenzyl)-1H-indole-2-carbonyl)spiro[chroman-2,4′-piperidin]-4-one (7d)

Yield 73% of white crystals; mp >300°C; ¹H NMR: δ 8.1 (d, J=1.5 Hz, 1H), 7.7 (d, J=8.1 Hz, 1H), 7.6 (dd, J=8.1 Hz and 1.5 Hz, 1H), 7.5 (m, 1H), 7.4 (dd, J=8.4 Hz and 1.3 Hz, 1H), 7.3 (d, J=8.5 Hz, 2H), 7.2 (s, 1H), 7.1 (d, J=8.5 Hz, 2H), 7.0 (m, 2H), 5.8 (s, 2H), 3.3–3.4 (m, 4H), 2.7 (s, 2H), 1.7–1.9 (m, 4H); ¹³C NMR: δ 33.7, 37.8, 43.6, 49.5, 68.0, 104.8, 113.7, 114.3, 119.1, 120.7, 123.7, 126.4, 126.9, 127.8, 128.5, 130.9, 132.3, 135.0, 137.8, 159.4, 164.7, 189.8; MS (ESI): m/e 562 (M)⁺, 564 (M+2)⁺, 566 (M+4)⁺. Anal. Calcd for C₂₉H₂₄BrClN₂O₃: C, 61.77; H, 4.29; N, 4.97. Found: C, 61.73, H, 4.23, N, 4.94.

7-Bromo-1′-(5-bromo-1-(4-chlorobenzyl)-1H-indole-2-carbonyl)spiro[chroman-2,4′-piperidin]-4-one (7e)

Yield 79% of white crystals; mp >300°C; ¹H NMR: δ 8.2 (d, J=1.5 Hz, 1H), 7.8 (d, J=8.1 Hz, 1H), 7.7 (dd, J=8.1 Hz and 1.5 Hz, 1H), 7.6 (d, J=8.2 Hz, 1H), 7.4 (d, J=1.3 Hz, 1H), 7.3 (d, J=8.5 Hz, 2H), 7.2 (dd, J=8.2 Hz and 1.3 Hz, 1H), 7.1 (s, 1H), 7.0 (d, J=8.5 Hz, 2H), 5.7 (s, 2H), 3.3–3.4 (m, 4H), 2.7 (s, 2H), 1.7–1.9 (m, 4H); ¹³C NMR: δ 33.8, 37.9, 43.7, 49.6, 57.7, 104.9, 113.6, 116.3, 120.0, 122.9, 123.7, 126.7, 127.0, 128.0, 128.7, 130.3, 130.5, 132.6, 135.3, 138.0, 159.6, 165.2, 190.1; MS (ESI): m/e 640 (M)⁺, 642 (M+2)⁺, 644 (M+4)⁺, 646 (M+6)⁺. Anal. Calcd for C₂₉H₂₃Br₂ClN₂O₃: C, 54.19; H, 3.61; N, 4.36. Found: C, 54.12; H, 3.58; N, 4.34.

5-Bromo-1-(4-chlorobenzyl)-N′-isonicotinoyl-1H-indole-2-carbohydrazide (7f)

Yield 79% of white crystals; mp 268–270°C; ¹H NMR: δ 9.0 (d, J=8.4 Hz, 2H), 8.5 (s, 2H), 8.0 (d, J=1.5 Hz, 1H), 7.9 (d, J=8.4 Hz, 2H), 7.8 (d, J=8.1 Hz, 1H), 7.7 (dd, J=8.1 Hz and 1.5 Hz, 1H), 7.4 (d, J=8.5 Hz, 2H), 7.3 (s, 1H), 7.2 (d, J=8.5 Hz, 2H), 5.8 (s, 2H); ¹³C NMR: δ 49.8, 68.7, 104.6, 113.5, 121.0, 123.8, 126.8, 127.9, 128.7, 131.5, 132.6, 135.3, 138.1, 140.7, 149.9, 161.3, 164.9; MS (ESI): m/e 482 (M)⁺, 484 (M+2)⁺, 486 (M+4)⁺. Anal. Calcd for C₂₂H₁₆BrClN₄O₂: C, 54.62; H, 3.33; N, 11.58. Found: C, 54.57; H, 3.29; N, 11.56.

tert-Butyl-4-(5-bromo-1-(4-chlorobenzyl)-1H-indole-2-carboxamido)piperidine-1-carboxylate (7g)

Yield 87% of white crystals; mp 290–292°C; ¹H NMR: δ 8.5 (d, 1H), 8.1 (d, J=1.5 Hz, 1H), 7.7 (d, J=8.1 Hz, 1H), 7.6 (dd, J=8.1 Hz and 1.5 Hz, 1H), 7.4 (d, J=8.5 Hz, 2H), 7.3 (s, 1H), 7.2 (d, J=8.5 Hz, 2H), 5.8 (s, 2H), 3.5 (m, 1H), 3.2–3.4 (m, 4H), 1.6–1.8 (m, 4H), 1.4 (s, 9H); ¹³C NMR: δ 27.9, 30.1, 43.1, 47.5, 49.6, 79.5, 104.7, 113.5, 123.7, 126.8, 127.9, 128.6, 131.5, 132.7, 138.2, 135.3, 159.1, 160.7. HRMS. Calcd for (M+H)⁺: m/z 546.1154. Found: m/z 546.1148.

5-Bromo-1-(4-chlorobenzyl)-N-cyclohexyl-1H-indole-2-carboxamide (7h)

Yield 94% of white crystals; mp 232–234°C; ¹H NMR: δ 8.3 (d, 1H), 8.2 (d, J=1.5 Hz, 1H), 7.8 (d, J=8.2 Hz, 1H), 7.7 (dd, J=8.2 Hz and 1.5 Hz, 1H), 7.4 (d, J=8.4 Hz, 2H), 7.3 (s, 1H), 7.2 (d, J=8.4 Hz, 2H), 5.8 (s, 2H), 3.6 (m, 1H), 1.5–1.7 (m, 5H), 1.2–1.3 (m, 5H); ¹³C NMR: δ 24.9, 25.5, 32.2, 49.4, 51.3, 1047, 113.6, 123.8, 126.8, 128.0, 128.4, 131.4, 132.8, 135.5, 138.3, 160.5. HRMS. Calcd for (M+H)⁺: m/z 445.0677. Found: m/z 445.0677.

5-Bromo-1-(4-chlorobenzyl)-N-cyclopentyl-1H-indole-2-carboxamide (7i)

Yield 92% of white crystals; mp 230–232°C; ¹H NMR: δ 8.4 (d, 1H), 8.1 (d, J=1.4 Hz, 1H), 7.7 (d, J=8.3 Hz, 1H), 7.6 (dd, J=8.3 Hz and 1.4 Hz, 1H), 7.4 (d, J=8.4 Hz, 2H), 7.3 (s, 1H), 7.2 (d, J=8.4 Hz, 2H), 5.8 (s, 2H), 3.6 (s, 1H), 1.6–1.8 (m, 4H), 1.3–1.5 (m, 4H); ¹³C NMR: δ 23.3, 32.7, 49.3, 56.3, 104.5, 113.6, 123.8, 126.7, 127.9, 128.2, 131.3, 132.8, 135.5, 138.4, 160.4; MS (ESI): m/e 430 (M)⁺, 432 (M+2)⁺, 434 (M+4)⁺. Anal. Calcd for C₂₁H₂₀BrClN₂O: C, 58.42; H, 4.67; N, 6.49. Found: C, 58.37; H, 4.60; N, 6.43.

5-Bromo-1-(4-chlorobenzyl)-N-phenyl-1H-indole-2-carboxamide (7j)

Yield 90% of white crystals; mp 238–240°C; ¹H NMR: δ 8.9 (b, 1H), 8.1 (s, 1H), 7.8 (dd, 1H), 7.7 (dd, 1H), 7.6 (d, 2H), 7.5 (d, 2H), 7.4 (s, 1H), 7.3 (d, 2H), 7.1 (d, 2H), 5.8 (s, 2H); ¹³C NMR: δ 49.2, 110.6, 113.7, 114.9, 120.6, 121.4, 123.5, 127.3, 128.2, 130.4, 133.1, 135.4, 137.2, 142.2, 162.4; MS (ESI): m/e 438 (M)⁺, 440 (M+2)⁺, 442 (M+4)⁺. Anal. Calcd for C₂₂H₁₆BrClN₂O: C, 60.09; H, 3.67; N, 6.37. Found: C, 60.03; H, 3.64; N, 6.31.

In vitro antibacterial activity

Compounds 7a–j were evaluated for their in vitro antibacterial activity against pathogenic Gram-negative bacteria K. pneumoniae (ATCC 27736), E. coli (ATCC 9637), P. aeruginosa (ATCC BAA427) and S. enterica subsp. enterica serovar Typhi (ATCC 19430) by using the broth microdilution technique described by the CLSI, 2012 [24]. Gentamicin and ciprofloxacin were used as standard drugs for comparison of antibacterial activity. DMSO was used as a solvent or negative control. To clarify any effect of DMSO on the antibacterial activity, separate studies were carried out with solutions of only DMSO and these studies showed no activity against any microbial strains. The MIC of tested compounds was determined using the 2-fold serial dilution technique by assaying at 51.2, 25.6, 12.8, 6.4, 3.2, 1.6, 0.8, 0.4, 0.2, 0.1 and 0.05 μg/mL concentrations along with standards at the same concentrations.

Acknowledgments

The authors are grateful to the Department of Postgraduate Studies and Research in Chemistry, Dnyanopasak College, Parbhani and Shri Chhatrapati Shivaji College, Omerga, for providing laboratory facilities and to the Indian Institute of Chemical Technology, Hyderabad, India, for spectral data.

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Received: 2018-06-23

Accepted: 2018-10-19

Published Online: 2018-11-13

Published in Print: 2018-12-19

This article is distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Articles in the same Issue

https://doi.org/10.1515/hc-2018-0107

Keywords for this article

antibacterial activity; indole; indole-2- carboxamide

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