Abstract
A series of benzothiazole and benzoxazole linked 1,4-disubstituted 1,2,3-triazoles was synthesized through copper(I) catalyzed azide-alkyne cycloaddition reaction. FTIR, 1H, 13C-NMR and HRMS techniques were used to examine the structure of synthesized derivatives. Further, these triazole derivatives were screened for in vitro antibacterial activities against two Gram-positive bacteria S. aureus, B. subtilis; two Gram-negative bacteria E. coli and K. pneumoniae by serial dilution technique, reflecting moderate to good activity. Compound 7s exhibited promising antibacterial activity among all the synthesized triazoles.
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1 Introduction
Heterocycles are an important class that is pervasive in vital bioactive molecules. Among various heterocycles, benzothiazole and benzoxazole compounds have been explored in past and are still in practice for a variety of therapeutic applications which makes this scaffold an interesting moiety for designing new broad-spectrum pharmacophore. Benzothiazole and benzoxazole and their derivatives have depicted various admirable biological properties in form of antioxidant,1 anticancer,2,3 anti-inflammatory,4 analgesic5 and acetylcholinesterase inhibitory6 agents. Some of the important marketed drugs having benzothiazole and benzoxazole ring in their structures are Riluzole, Pramipexole, flunoxaprofen, benoxaprofen (Figures 1, 2, 3, 4), etc.
Riluzole.
Pramipexole.
Flunoxaprofen.
Benoxaprofen.
Molecules having triazole nucleus leads to diversified applications in medicine, agriculture, etc. The triazole derivatives have been found to possess immense biological importance like antitubercular,7 anti-cancer,8,9,10,11,12,–13 antiparasitic,14 antimicrobial,15,16,17,18,19,20,21,–22 antileishmanial,23 antioxidant,24,25 anti-inflammatory,26,27,28,–29 and anti-malarial,30 α-glycosidase inhibitory,31 antiviral,32 antidepressant,33 acetylcholinesterase inhibitory34,35 activities have been identified. Triazole nucleus enjoys its importance as the core structure of blockbuster drugs such as fluconazole, Rufinamide, Cefatrizine, etc. In recent years, the chemistry of triazoles and its heterocyclic derivatives led to the development of lead compounds in medicinal chemistry. Owing to this, here click reaction has been used for the formation (synthesis) of 1,4-disubstituted 1,2,3-triazoles from azides and terminal alkynes. “Click” chemistry approach has been formulated to insert a link between triazole nucleus and benzothiazole and benzoxazole moiety with a thought to explore the synergic effect of these two scaffolds. The synthesized 1,2,3-triazoles containing benzothiazole and benzoxazole have also been explored for antibacterial activity against Staphylococcus aureus, Bacillus subtilis, Klebsiella pneumoniae and Escherichia coli.
2 Experimental
2.1 Chemistry
The starting materials were purchased from Sigma-Aldrich, Alfa-Aesar, Hi-Media and used without any further purification. Melting points (°C) were determined by an open capillaries method and uncorrected. To monitor the progress of the reaction and to check the purity of compounds, thin-layer chromatography (TLC) was performed using silica gel plates (SIL G/UV254, ALUGRAM). The IR spectra were taken on SHIMAZDU IR AFFINITY-I FTIR spectrometer using potassium bromide (KBr) powder and values are given in cm−1. Nuclear magnetic resonance (NMR) spectra were recorded on BRUKER AVANCE II apparatus operating at 400 MHz (1H) and 100 MHz (13C), in DMSO, and chemical shifts (δ) are given in parts per million downfield from the internal standard trimethylsilane (TMS). Coupling constant (J) values were observed in Hertz (Hz). HRMS were observed on Bruker micro TOF Q-II spectrometer.
General procedure for the synthesis of terminal Alkyne36,37(3a-3b): The 2-(prop-2-yn-1-ylthio)benzo[d]oxazole(3a)/2-(prop-2-yn-1-ylthio)benzo[d]thiazole (3b) were synthesized by dropwise addition of propargyl bromide (2) (1.0 mmol) to the solution of 2-mercaptobenzoxazole (1a)/2-mercaptobenzothiazole (1b) (1.0 mmol) in N,N-dimethylformamide in presence of potassium carbonate as base at 0-10 °C for 3 h. After the completion of the reaction, the cooled reaction mixture was poured in ice-cold water and the precipitated products were filtered to get the desired alkynes (3a-3b).
General procedure for the synthesis of 4-(bromomethyl)-N-arylbenzamide derivatives (6a-6j): The aromatic amines (5a-5j) (1.0 mmol) were reacted with 4-(bromomethyl)benzoylbromide (4) (1.0 mmol) in dichloromethane and potassium carbonate as a base at 0-10 °C for 2-3 h. After the completion of the reaction as indicated by TLC, the product was extracted with dichloromethane and the organic layer was dried with anhydrous sodium sulphate and concentrated under reduced pressure to obtain 4-(bromomethyl)-N-arylbenzamide derivatives (6a-6j) with 80-90% yield.
General procedure for the synthesis of 1,4-disubstituted 1,2,3-triazole derivatives (7a-7t): The targeted 1,4-disubstituted 1,2,3-triazoles with amide and thioether functionality were synthesized by the reaction of 2-(prop-2-yn-1-ylthio)benzo[d]oxazole (3a)/2-(prop-2-yn-1-ylthio)benzo[d]thiazole (3b) (1.0 mmol), 4-(bromomethyl)-N-arylbenzamide derivatives (6a-6j) (1.0 mmol) and sodium azide using dimethylformamide:water as a solvent in the presence of the catalytic amount of copper sulphate pentahydrate and sodium ascorbate with stirring for 6–10 h at ambient temperature. After the completion of the reaction, the reaction mixture was quenched with ice-cold water and ammonia solution, the precipitates were filtered and recrystallized from ethyl acetate to yield the pure 1,4-disubstituted 1,2,3-triazoles (7a-7t).
2.2 Characterization of benzothiazole and benzoxazole linked 1,4-disubstituted 1,2,3-triazoles
2.2.1 4-((4-((benzo[d]oxazol-2-ylthio)methyl)-1H-1,2,3-triazol-1-yl)methyl)-N-phenylbenzamide (7a)
Appearance: Brown solid; yield: 79%; M.p.: 152–156 °C; FTIR (KBr): νmax = 3336 (N–H str.), 3143 (C–H str., triazole ring), 2881 (C–H str., aliphatic), 1653 (C=O sym. str., amide), 1500, 1442 (C=C str., aromatic ring), 692 (C–S str.) cm−1; 1H NMR (400 MHz, DMSO-d6) δ 10.23 (s, 1H, -CONH), 8.24 (s, 1H, C-H triazole), 8.02 (d, J = 8.0 Hz, 1H, ArH), 7.91 (d, J = 8.0 Hz, 2H, ArH), 7.76 (d, J = 8.0 Hz, 1H, ArH), 7.48 (t, J = 8.0, 1H, ArH), 7.41-7.08 (m, 7H, ArH), 5.68 (s, 2H,-NCH2), 4.71 (s, 2H, -SCH2); 13C NMR (100 MHz, DMSO) δ 165.56 (C=O), 151.81, 143.14 (C4 triazole), 141.71, 139.76, 139.53, 135.25, 129.06, 128.55, 128.25, 125.12, 124.85, 124.62 (C5 triazole), 124.17, 120.79, 118.85, 110.73, 52.90 (-SCH2), 26.95 (-NCH2); HRMS (m/z) calculated for C24H19N5O2S [M+H]+: 442.1293. Found: 442.1318.
2.2.2 4-((4-((benzo[d]oxazol-2-ylthio)methyl)-1H-1,2,3-triazol-1-yl)methyl)-N-(o-tolyl)benzamide (7b)
Appearance: White solid; yield: 81%; M.p.: 152–156 °C; FTIR (KBr): νmax = 3257 (N–H str.), 3124 (C–H str., triazole ring), 2983 (C–H str., aliphatic), 1643 (C=O sym. str., amide), 1500, 1452 (C=C str., aromatic ring), cm−1; 1H NMR (400 MHz, DMSO-d6) δ 9.83 (s, 1H, -CONH), 8.22 (s, 1H, C-H triazole), 7.88 (d, J = 8.0 Hz, 2H), 7.625 (d, J = 4.0 Hz, 2H, ArH), 7.36 (d, J = 8.0 Hz, 2H, ArH), 7.32-7.26 (m, 3H, ArH), 7.23 (d, J = 8.0 Hz, 1H, ArH), 7.19-7.12 (m, 2H, ArH), 5.63 (s, 2H,-NCH2), 4.65 (s, 2H, -SCH2), 2.17 (s, 3H, -CH3). 13C NMR (100 MHz, DMSO) δ 165.36 (C=O), 151.85, 143.21(C4 triazole), 141.75, 130.85, 130.85, 128.60, 128.39, 127.07, 126.55, 125.20, 124.93, 124.73 (C5 triazole), 118.91, 110.82, 52.93 (-SCH2), 26.96 (-NCH2), 18.40; HRMS (m/z) calculated for C25H21 N5O2S [M+H]+: 456. 1450. Found: 456.1493.
2.2.3 4-((4-((benzo[d]oxazol-2-ylthio)methyl)-1H-1,2,3-triazol-1-yl)methyl)-N-(m-tolyl)benzamide (7c)
Appearance: White solid; yield: 85%; M.p.: 152–156 °C; FTIR (KBr): νmax = 3346 (N–H str.), 3115 (C–H str., triazole ring), 2918 (C–H str., aliphatic), 1653 (C=O sym. str., amide), 1527, 1440 (C=C str., aromatic ring), cm−1; 1H NMR (400 MHz, DMSO-d6) δ 10.14 (s, 1H, -CONH), 8.22 (s, 1H, C-H triazole), 7.85 (d, J = 8.0 Hz, 2H, ArH), 7.64-7.58 (m, 3H, ArH), 7.35 (d, J = 8.0 Hz, 2H, ArH), 7.30 (t, J = 8.0 Hz, 2H, ArH), 7.20 (s, 1H, ArH), 7.11 (d, J = 8.0 Hz, 2H), 5.63 (s, 2H,-NCH2), 4.65 (s, 2H, -SCH2), 2.23 (s, 3H, -CH3). 13C NMR (100 MHz, DMSO) δ 166.22 (C=O), 165.42, 153.09, 143.30 (C4 triazole), 139.79, 137.06, 135.24, 133.19, 129.54, 128.56, 128.28, 126.92, 125.11, 124.80 (C5 triazole), 122.38, 121.80, 120.84, 52.91 (-SCH2), 27.94 (-NCH2), 21.03; HRMS (m/z) calculated for C25H21 N5O2S [M+H]+: 456. 1450. Found: 456.1506.
2.2.4 4-((4-((benzo[d]oxazol-2-ylthio)methyl)-1H-1,2,3-triazol-1-yl)methyl)-N-(p-tolyl)benzamide (7d)
Appearance: White solid; yield: 82%; M.p.: 152–156 °C; FTIR (KBr): νmax = 3361 (N–H str.), 3109 (C–H str., triazole ring), 2951 (C–H str., aliphatic), 1643 (C=O sym. str., amide), 1517, 1423 (C=C str., aromatic ring), cm−1; 1H NMR (400 MHz, DMSO-d6) δ 10.11 (s, 1H, -CONH), 8.22 (s, 1H, C-H triazole), 7.84 (d, J = 8.0 Hz, 2H, ArH), 7.62 (d, J = 8.0 Hz, 2H), 7.55 (s, 1H, ArH), 7.50 (d, J = 8.0 Hz, 1H, ArH), 7.35 (d, J = 8.0 Hz, 2H, ArH), 7.30 (m, 2H, ArH), 7.18 (m, 1H, ArH), 6.88 (d, J = 8.0 Hz, 1H, ArH), 5.63 (s, 2H,-NCH2), 4.65 (s, 2H, -SCH2), 2.26 (s, 3H, -CH3); 13C NMR (100 MHz, DMSO) δ 165.66 (C=O), 151.92, 143.23 (C4 triazole), 141.74, 139.83, 139.50, 138.30, 135.31, 129.00, 128.60, 128.32, 125.21, 124.93, 124.74 (C5 triazole), 121.35, 118.91, 118.00, 110.82, 52.92 (-SCH2), 26.96 (-NCH2), 21.74; HRMS (m/z) calculated for C25H21 N5O2S [M+H]+: 456. 1450. Found: 456.1503.
2.2.5 4-((4-((benzo[d]oxazol-2-ylthio)methyl)-1H-1,2,3-triazol-1-yl)methyl)-N-(4-methoxyphenyl)benzamide (7e)
Appearance: White solid; yield: 83%; M.p.: 152–156 °C; FTIR (KBr): νmax = 3311 (N–H str.), 3115 (C–H str., triazole ring), 2954 (C–H str., aliphatic), 1645 (C=O sym. str., amide), 1508, 1409 (C=C str., aromatic ring), cm−1; 1H NMR (400 MHz, DMSO-d6) δ 10.22 (s, 1H, -CONH), 8.28 (s, 1H, C-H triazole), 7.93 (s, 1H, ArH), 7.67-7.42 (m, 10H, ArH), 6.92 (s, 1H, ArH), 5.67 (s, 2H,-NCH2), 4.67 (s, 2H, -SCH2), 3.24 (s, 3H, -OCH3); 13C NMR (100 MHz, DMSO) δ 165.14 (C=O), 156.03, 143.13 (C4 triazole), 141.79, 139.61, 135.16, 132.62, 128.51, 128.20, 125.13, 124.86, 124.72 (C5 triazole), 122.47, 118.84, 114.16, 110.75, 55.64, 52.87 (-SCH2), 26.92 (-NCH2); HRMS (m/z) calculated for C25H21 N5O3S [M+H]+: 472. 1399. Found: 472.1446.
2.2.6 4-((4-((benzo[d]oxazol-2-ylthio)methyl)-1H-1,2,3-triazol-1-yl)methyl)-N-(4-nitrophenyl)benzamide (7f)
Appearance: White solid; yield: 78%; M.p.: 152–156 °C; FTIR (KBr): νmax = 3354 (N–H str.), 3107 (C–H str., triazole ring), 2942 (C–H str., aliphatic), 1658 (C=O sym. str., amide), 1504, 1406 (C=C str., aromatic ring), cm−1; 1H NMR (400 MHz, DMSO-d6) δ 10.77 (s, 1H, -CONH), 8.29 (s, 1H, C-H triazole), 8.26 (m, 2H, ArH), 8.045 (d, J = 12.0 Hz, 2H, ArH), 7.93 (d, J = 8.0 Hz, 2H, ArH), 7.69– 7.62 (m, 2H, ArH), 7.43 (d, J = 8.0 Hz, 2H, ArH), 7.39–7.30 (m, 2H, ArH), 5.69 (s, 2H,-NCH2), 4.69 (s, 2H, -SCH2). 13C NMR (100 MHz, DMSO) δ 166.31 (C=O), 151.81, 145.84, 143.00 (C4 triazole), 141.71, 140.45, 134.48, 128.83, 128.36, 125.26, 125.12, 124.85, 124.66 (C5 triazole), 120.31, 118.85, 110.73, 52.87 (-SCH2), 26.95 (-NCH2); HRMS (m/z) calculated for C24H18 N6O2S [M+H]+: 487. 1144. Found: 487.1177.
2.2.7 4-((4-((benzo[d]oxazol-2-ylthio)methyl)-1H-1,2,3-triazol-1-yl)methyl)-N-(4-fluorophenyl)benzamide (7g)
Appearance: Brown solid; yield: 81%; M.p.: 152–156 °C; FTIR (KBr): νmax = 3365 (N–H str.), 3128 (C–H str., triazole ring), 3078 (C–H str., aliphatic), 1660 (C=O sym. str., amide), 1508, 1450 (C=C str., aromatic ring), 685 (C–S str.) cm−1; 1H NMR (400 MHz, DMSO-d6) δ 10.26 (s, 1H, -CONH), 8.25 (s, 1H, C-H triazole), 7.90 (d, J = 8.0 Hz, 2H, ArH), 7.77 (dd, J = 8.0, 4.0 Hz, 2H, ArH), 7.67-7.65 (m, 2H, ArH), 7.40 (d, J = 8.0 Hz, 2H, ArH),7.36-7.33 (m, 2H, ArH) 7.22-7.18 (m, 2H, ArH), 5.68 (s, 2H,-NCH2), 4.69 (s, 2H, -SCH2); 13C NMR (100 MHz, DMSO) δ 165.48 (C=O), 163.96, 151.82, 143.15 (C4 triazole), 141.72, 139.84, 135.92, 135.07, 128.53, 128.28, 125.13, 124.86, 124.63 (C5 triazole), 122.66, 122.59, 118.86, 115.76, 115.54, 110.73, 52.89 (-SCH2), 26.96 (-NCH2); HRMS (m/z) calculated for C24H18 FN5O2S [M+H]+: 460. 1199. Found: 460.1254.
2.2.8 4-((4-((benzo[d]oxazol-2-ylthio)methyl)-1H-1,2,3-triazol-1-yl)methyl)-N-(4-chlorophenyl)benzamide (7h)
Appearance: White solid; yield: 77%; M.p.: 152–156 °C; FTIR (KBr): νmax = 3298 (N–H str.), 3132 (C–H str., triazole ring), 2848 (C–H str., aliphatic), 1654 (C=O sym. str., amide), 1498, 1454 (C=C str., aromatic ring), cm−1; 1H NMR (400 MHz, DMSO-d6) δ 10.40 (s, 1H, -CONH), 8.27 (s, 1H, C-H triazole), 8.04 (d, J = 8.0 Hz, 1H, ArH), 7.98 (d, J = 8.0 Hz, 2H, ArH), 7.87 (d, J = 8.0 Hz, 1H, ArH), 7.69–7.65 (m, 2H, ArH), 7.62-7.53 (m, 3H, ArH), 7.44 (d, J = 8.0 Hz, 1H, ArH), 7.37–7.33 (m, 2H, ArH), 5.71 (s, 2H,-NCH2), 4.71 (s, 2H, -SCH2). 13C NMR (100 MHz, DMSO) δ 166.19 (C=O), 163.96, 151.82, 143.15 (C4 triazole), 141.73, 139.87, 134.75, 134.23, 129.60, 128.71, 128.53, 128.34, 126.76, 126.53, 126.43, 125.99, 125.12, 124.85, 124.65 (C5 triazole), 124.26, 123.74, 118.86, 110.73, 52.94 (-SCH2), 26.98 (-NCH2); HRMS (m/z) calculated for C24H18 ClN5O2S [M+H]+: 476.0870, [M+3]+: 478.0840. Found: 476.0934, [M+3]+: 478.0898.
2.2.9 4-((4-((benzo[d]oxazol-2-ylthio)methyl)-1H-1,2,3-triazol-1-yl)methyl)-N-(4-bromophenyl)benzamide (7i)
Appearance: White solid; yield: 86%; M.p.: 152–156 °C; FTIR (KBr): νmax = 3304 (N–H str.), 3120 (C–H str., triazole ring), 2945 (C–H str., aliphatic), 1651 (C=O sym. str., amide), 1527, 1452 (C=C str., aromatic ring), cm−1; 1H NMR (400 MHz, DMSO-d6) δ 10.36 (s, 1H, -CONH), 8.25 (s, 1H, C-H triazole), 7.90 (d, J = 8.0 Hz, 2H, ArH), 7.755 (d, J = 12.0 Hz, 2H, ArH), 7.68–7.64 (m, 2H, ArH), 7.535 (d, J = 12.0 Hz, 2H, ArH), 7.40 (d, J = 8.0 Hz, 2H, ArH), 7.37–7.31 (m, 2H, ArH), 5.68 (s, 2H,-NCH2), 4.69 (s, 2H, -SCH2); 13C NMR (100 MHz, DMSO) δ 165.66 (C=O), 163.94, 151.81, 143.14 (C4 triazole), 141.71, 139.95, 138.96, 134.93, 131.89, 128.60, 128.27, 125.11, 124.84, 124.63 (C5 triazole), 122.67, 118.85, 115.83, 110.73, 52.88 (-SCH2), 26.96 (-NCH2); HRMS (m/z) calculated for C24H18 BrN5O2S [M+H]+: 520.0365, [M+3]+: 522.0344. Found [M+H]+: 520.0407, [M+3]+: 522.0405.
2.2.10 4-((4-((benzo[d]oxazol-2-ylthio)methyl)-1H-1,2,3-triazol-1-yl)methyl)-N-(naphthalen-1-yl)benzamide (7j)
Appearance: White solid; yield: 76%; M.p.: 152–156 °C; FTIR (KBr): νmax = 3296 (N–H str.), 3113 (C–H str., triazole ring), 2984 (C–H str., aliphatic), 1654 (C=O sym. str., amide), 1539, 1450 (C=C str., aromatic ring), cm−1; 1H NMR (400 MHz, DMSO-d6) δ 10.36 (s, 1H, -CONH), 8.25 (s, 1H, C-H triazole), 7.90 (d, J = 8.0 Hz, 2H, ArH), 7.81 (d, J = 8.0 Hz, 2H, ArH), 7.67–7.64 (m, 2H, ArH), 7.44– 7.38 (m, 4H, ArH), 7.37–7.20 (m, 5H, ArH), 5.68 (s, 2H,-NCH2), 4.69 (s, 2H, -SCH2). 13C NMR (100 MHz, DMSO) δ 165.66 (C=O), 163.94, 151.81, 143.14 (C4 triazole), 141.71, 139.94, 138.54, 134.94, 128.98, 128.60, 128.28, 125.12, 124.85, 124.63 (C5 triazole), 122.30, 118.85, 110.73, 52.88 (-SCH2), 26.96 (-NCH2); HRMS (m/z) calculated for C28H21 N5O2S [M+H]+: 492. 1450. Found: 492.1486.
2.2.11 4-((4-((benzo[d]thiazol-2-ylthio)methyl)-1H-1,2,3-triazol-1-yl)methyl)-N-phenylbenzamide (7k)
Appearance: White solid; yield: 75%; M.p.: 152–156 °C; FTIR (KBr): νmax = 3363 (N–H str.), 3140 (C–H str., triazole ring), 3062 (C–H str., aliphatic), 1653 (C=O sym. str., amide), 1506, 1440 (C=C str., aromatic ring), cm−1; 1H NMR (400 MHz, DMSO-d6) δ 10.23 (s, 1H, -CONH), 8.24 (s, 1H, C-H triazole), 8.02 (d, J = 8.0 Hz, 1H, ArH), 7.91 (d, J = 8.0 Hz, 2H, ArH), 7.76 (d, J = 8.0 Hz, 1H, ArH), 7.48 (t, J = 8.0, 1H, ArH), 7.41-7.08 (m, 8H, ArH), 5.68 (s, 2H,-NCH2), 4.71 (s, 2H, -SCH2); 13C NMR (100 MHz, DMSO) δ 165.54 (C=O), 143.09 (C4 triazole)135.21, 129.05, 128.56, 128.22, 126.84, 125.03, 124.70 (C5 triazole), 122.29, 121.75, 120.81, 113.73, 52.88 (-SCH2), 26.90 (-NCH2); HRMS (m/z) calculated for C24H19N5OS2 [M+H]+: 458. 1065. Found: 458.1098.
2.2.12 4-((4-((benzo[d]thiazol-2-ylthio)methyl)-1H-1,2,3-triazol-1-yl)methyl)-N-(o-tolyl)benzamide (7l)
Appearance: White solid; yield: 82%; M.p.: 152–156 °C; FTIR (KBr): νmax = 3361 (N–H str.), 3109 (C–H str., triazole ring), 2951 (C–H str., aliphatic), 1643 (C=O sym. str., amide), 1517, 1423 (C=C str., aromatic ring), cm−1; 1H NMR (400 MHz, DMSO-d6) δ 9.85 (s, 1H, -CONH), 9.18 (s, 1H, C-H triazole), 8.47 (d, J = 8.0 Hz, 1H, ArH), 8.39 (d, J = 8.0 Hz, 1H, ArH), 8.15 (d, J = 8.0 Hz, 1H, ArH), 8.08-8.01 (m, 2H, ArH), 7.62–7.45 (m, 5H, ArH), 7.42–7.34 (t, J = 8.0 Hz, 2H, ArH), 5.67 (s, 2H, -NCH2), 4.72 (s, 2H, -SCH2), 2.67 (s, 3H). 13C NMR (100 MHz, DMSO) δ 165.36 (C=O), 151.85, 143.21 (C4 triazole), 141.75, 130.85, 130.85, 128.60, 128.39, 127.07, 126.55, 125.20, 124.93, 124.73 (C5 triazole), 118.91, 110.82, 52.93 (-SCH2), 26.96 (-NCH2), 18.40; HRMS (m/z) calculated for C25H21N5OS2 [M+H]+: 472. 1221. Found: 472.1271.
2.2.13 4-((4-((benzo[d]thiazol-2-ylthio)methyl)-1H-1,2,3-triazol-1-yl)methyl)-N-(m-tolyl)benzamide (7m)
Appearance: White solid; yield: 79%; M.p.: 152–156 °C; FTIR (KBr): νmax = 3361 (N–H str.), 3124 (C–H str., triazole ring), 2942 (C–H str., aliphatic), 1645 (C=O sym. str., amide), 1521, 1423 (C=C str., aromatic ring), cm−1; 1H NMR (400 MHz, DMSO-d6) δ 9.83 (s, 1H, -CONH), 8.22 (s, 1H, C-H triazole), 7.88 (d, J = 8.0 Hz, 2H), 7.62 (d, J = 8.0 Hz, 2H, ArH), 7.36 (d, J = 8.0 Hz, 2H, ArH), 7.32-7.26 (m, 3H, ArH), 7.23 (d, J = 8.0 Hz, 1H, ArH), 7.19-7.12 (m, 2H, ArH), 5.63 (s, 2H,-NCH2), 4.65 (s, 2H, -SCH2), 2.17 (s, 3H, -CH3). 13C NMR (100 MHz, DMSO) δ 165.36 (C=O), 151.85, 143.21 (C4 triazole), 141.75, 130.85, 130.85, 128.60, 128.39, 127.07, 126.55, 125.20, 124.93, 124.73 (C5 triazole), 118.91, 110.82, 52.93 (-SCH2), 26.96 (-NCH2), 18.40; HRMS (m/z) calculated for C25H21N5OS2 [M+H]+: 472. 1221. Found: 472.1271.
2.2.14 4-((4-((benzo[d]thiazol-2-ylthio)methyl)-1H-1,2,3-triazol-1-yl)methyl)-N-(p-tolyl)benzamide (7n)
Appearance: Brown solid; yield: 80%; M.p.: 152–156 °C; FTIR (KBr): νmax = 3361 (N–H str.), 3120 (C–H str., triazole ring), 2956 (C–H str., aliphatic), 1651 (C=O sym. str., amide), 1508, 1408 (C=C str., aromatic ring), cm−1; 1H NMR (400 MHz, DMSO-d6) δ 10.14 (s, 1H, -CONH), 8.22 (s, 1H, C-H triazole), 7.85 (d, J = 8.0 Hz, 2H, ArH), 7.64-7.58 (m, 3H, ArH), 7.35 (d, J = 8.0 Hz, 2H, ArH), 7.30 (t, J = 4.0 Hz, 2H, ArH), 7.20 (s, 1H, ArH), 7.11 (d, J = 8.0 Hz, 2H), 5.63 (s, 2H,-NCH2), 4.65 (s, 2H, -SCH2), 2.23 (s, 3H, -CH3). 13C NMR (100 MHz, DMSO) δ 165.41 (C=O), 164.03, 151.85, 143.20 (C4 triazole), 141.74, 139.76, 137.07, 135.32, 133.18, 129.53, 128.58, 128.30, 125.20, 124.92, 124.73 (C5 triazole), 120.85, 118.91, 110.82, 52.92 (-SCH2), 26.96 (-NCH2), 21.03; HRMS (m/z) calculated for C25H21N5OS2 [M+H]+: 472. 1221. Found: 472.1271.
2.2.15 4-((4-((benzo[d]thiazol-2-ylthio)methyl)-1H-1,2,3-triazol-1-yl)methyl)-N-(4-methoxyphenyl)benzamide (7o)
Appearance: Brown solid; yield: 83%; M.p.: 152–156 °C; FTIR (KBr): νmax = 3361 (N–H str.), 3109 (C–H str., triazole ring), 2951 (C–H str., aliphatic), 1643 (C=O sym. str., amide), 1517, 1423 (C=C str., aromatic ring), cm−1; 1H NMR (400 MHz, DMSO-d6) δ 10.07 (s, 1H, -CONH), 8.20 (s, 1H, C-H triazole), 7.98 (d, J = 8.0 Hz, 1H, ArH), 7.84 (m, 3H, ArH), 7.61 (d, J = 8.0 Hz, 2H, ArH), 7.44 (t, J = 8.0 Hz, 2H, ArH), 7.36-7.32 (m, 2H, ArH), 6.88 (d, J = 8.0 Hz, 2H, ArH), 5.63 (s, 2H,-NCH2), 4.67 (s, 2H, -SCH2), 3.70 (s, 3H, -OCH3). 13C NMR (100 MHz, DMSO) δ 166.33 (C=O), 153.23, 144.97 (C4 triazole), 139.71, 135.24, 132.79, 128.50, 128.28, 126.93, 125.11(C5 triazole), 122.42, 121.80, 114.26, 55.68, 52.91(-SCH2), 28.08 (-NCH2); HRMS (m/z) calculated for C25H21N5OS2 [M+H]+: 488.1170. Found: 488.1203.
2.2.16 4-((4-((benzo[d]thiazol-2-ylthio)methyl)-1H-1,2,3-triazol-1-yl)methyl)-N-(4-nitrophenyl)benzamide (7p)
Appearance: White solid; yield: 72%; M.p.: 152–156 °C; FTIR (KBr): νmax = 3356 (N–H str.), 3112 (C–H str., triazole ring), 2953 (C–H str., aliphatic), 1658 (C=O sym. str., amide), 1506, 1423 (C=C str., aromatic ring), cm−1; 1H NMR (400 MHz, DMSO-d6) δ 10.75 (s, 1H, -CONH), 8.26 – 8.20 (m, 3H, C-H triazole, ArH), 7.99 (t, J = 8.0 Hz, 3H, ArH), 7.86 (t, J = 8.0 Hz, 3H, ArH), 7.46 – 7.30 (m, 4H, ArH), 5.65 (s, 2H,-NCH2), 4.67 (s, 2H, -SCH2). 13C NMR (100 MHz, DMSO) δ 166.30 (C=O), 164.16, 151.56, 143.52 (C4 triazole), 128.91, 128.41, 126.92, 125.37, 125.11, 124.84 (C5 triazole), 122.38, 121.80, 120.34, 52.88 (-SCH2), 27.93 (-NCH2); HRMS (m/z) calculated for C24H18N6O3S2 [M+H]+: 503. 0915. Found: 503.0951.
2.2.17 4-((4-((benzo[d]thiazol-2-ylthio)methyl)-1H-1,2,3-triazol-1-yl)methyl)-N-(4-fluorophenyl)benzamide (7q)
Appearance: White solid; yield: 81%; M.p.: 152–156 °C; FTIR (KBr): νmax = 3361 (N–H str.), 3107 (C–H str., triazole ring), 3062 (C–H str., aliphatic), 1651 (C=O sym. str., amide), 150, 1458 (C=C str., aromatic ring), cm−1; 1H NMR (400 MHz, DMSO-d6) δ 10.25 (s, 1H, -CONH), 8.23 (s, 1H, C-H triazole), 8.02 (d, J = 8.0 Hz, 1H, ArH), 7.89 (d, J = 8.0 Hz, 3H, ArH), 7.79-7.73 (m, 2H, ArH), 7.51-7.46 (m, 1H, ArH), 7.42- 7.35 (m, 3H, ArH), 7.23-7.16 (m, 2H, ArH), 5.68 (s, 2H,-NCH2), 4.71 (s, 2H, -SCH2). 13C NMR (100 MHz, DMSO) δ 165.00 (C=O), 163.33, 152.16, 145.86 (C4 triazole), 141.25, 139.92, 137.23, 135.10, 128.51, 128.25, 126.84, 125.03, 124.68 (C5 triazole), 123.32, 122.65, 122.58, 122.28, 121.74, 116.21, 115.76, 115.54, 52.92 (-SCH2), 27.96 (-NCH2); HRMS (m/z) calculated for C24H18FN5OS2 [M+H]+: 476. 0970. Found: 476.1016.
2.2.18 4-((4-((benzo[d]thiazol-2-ylthio)methyl)-1H-1,2,3-triazol-1-yl)methyl)-N-(4-chlorophenyl)benzamide (7r)
Appearance: White solid; yield: 78%; M.p.: 152–156 °C; FTIR (KBr): νmax = 3284 (N–H str.), 3115 (C–H str., triazole ring), 2939 (C–H str., aliphatic), 1656 (C=O sym. str., amide), 1539, 1419 (C=C str., aromatic ring), cm−1; 1H NMR (400 MHz, DMSO-d6) δ 10.35 (s, 1H, -CONH), 8.23 (s, 1H, C-H triazole), 8.02 (d, J = 8.0 Hz, 1H, ArH), 7.98–7.87 (m, 3H, ArH), 7.81 (d, J = 8.0 Hz, 2H, ArH), 7.56–7.44 (m, 1H, ArH), 7.45–7.35 (m, 5H, ArH), 5.68 (s, 2H,-NCH2), 4.71 (s, 2H, -SCH2). 13C NMR (100 MHz, DMSO) δ 166.11 (C=O), 165.65, 153.06, 143.23 (C4 triazole), 139.97, 138.54, 135.20, 134.93, 128.98, 128.59, 128.25, 127.77, 126.84, 125.03, 124.70 (C5 triazole), 122.29, 121.74, 52.87, 40.67, 40.46, 40.25, 40.04, 39.83, 39.63, 39.42, 27.96; HRMS (m/z) calculated for C24H18ClN5OS2 [M+H]+: 492.0641, [M+3]+: 494.0612. Found: 492.0707, [M+3]+: 494.0676.
2.2.19 4-((4-((benzo[d]thiazol-2-ylthio)methyl)-1H-1,2,3-triazol-1-yl)methyl)-N-(4-bromophenyl) benzamide (7s)
Appearance: White solid; yield: 73%; M.p.: 152–156 °C; FTIR (KBr): νmax = 3284 (N–H str.), 3111 (C–H str., triazole ring), 2946 (C–H str., aliphatic), 1654 (C=O sym. str., amide), 1527, 1425 (C=C str., aromatic ring), cm−1; 1H NMR (400 MHz, DMSO-d6) δ 10.33 (s, 1H, -CONH), 8.23 (s, 1H, C-H triazole), 8.02 (d, J = 8.0 Hz, 1H), 7.89 (d, J = 8.0 Hz, 3H), 7.75 (d, J = 8.0 Hz, 2H), 7.54 (d, J = 8.0 Hz, 2H), 7.48 (t, J = 8.0 Hz, 1H), 7.42-7.34 (m, 3H), 5.68 (s, 2H,-NCH2), 4.71 (s, 2H, -SCH2). 13C NMR (100 MHz, DMSO) δ 165.68 (C=O), 153.06, 143.25 (C4 triazole), 140.00, 138.96, 135.21, 131.92, 128.59, 128.27, 126.85, 125.04, 124.71 (C5 triazole), 122.65, 122.30, 121.75, 52.87 (-SCH2), 27.95 (-NCH2); HRMS (m/z) calculated for C24H18BrN5OS2 [M+H]+: 536.0136, [M+3]+: 538.0116. Found: [M+H]+: 536.0183, [M+3]+: 538.0185.
2.2.20 4-((4-((benzo[d]thiazol-2-ylthio)methyl)-1H-1,2,3-triazol-1-yl)methyl)-N-(naphthalen-1-yl)benzamide (7t)
Appearance: Brown solid; yield: 85%; M.p.: 152–156 °C; FTIR (KBr): νmax = 3305 (N–H str.), 3115 (C–H str., triazole ring), 2954 (C–H str., aliphatic), 1647 (C=O sym. str., amide), 1529, 1429 (C=C str., aromatic ring), cm−1; 1H NMR (400 MHz, DMSO-d6) δ 10.40 (s, 1H, -CONH), 8.26 (s, 1H, C-H triazole), 8.06-8.01 (m, 2H, ArH), 7.98 (t, J = 8.0 Hz, 2H, ArH), 7.89 (dd, J = 16.0, 8.0 Hz, 2H, ArH), 7.63–7.53 (m, 5H, ArH), 7.49 (t, J = 8.0 Hz, 1H, ArH), 7.44 (d, J = 8.0 Hz, 2H, ArH), 7.38 (t, J = 16.0 Hz, 1H, ArH), 5.71 (s, 2H,-NCH2), 4.73 (s, 2H, -SCH2). 13C NMR (100 MHz, DMSO) δ 166.19 (C=O), 166.12, 153.07, 143.25 (C4 triazole), 139.91, 135.22, 134.73, 134.23, 129.60, 128.70, 128.53, 128.32, 126.85, 126.76, 126.53, 126.43, 126.00, 125.04, 124.73 (C5 triazole), 124.27, 123.74, 122.29, 121.76, 52.93 (-SCH2), 27.98 (-NCH2); HRMS (m/z) calculated for C28H21N5OS2 [M+H]+: 508. 1221. Found: 508.1253.
2.3 General procedure for in vitro antibacterial evaluation
All the newly synthesized triazole derivatives were screened for in vitro antibacterial activity against S. aureus (MTCC 7443), B. subtilis (MTCC 441) as Gram-positive bacterial strains and E. coli (MTCC 1231), K. pneumoniae (NCDC 138) as Gram-negative bacterial strains, by standard serial dilution technique.38 Stock solution of 200 µg/mL concentration was prepared by dissolving 2.0 mg of the synthesized compound in 10 mL of DMSO. The fresh nutrient broth was used as a culture media for bacterial strains. Firstly, 1 mL of nutrient broth was taken in each test tube. Then, 1 mL of stock solution was added in the first test tube to get the solution of 100 µg/mL concentration. From this solution, concentrations of 50–6.25 µg/mL were obtained in other test tubes through serial dilution technique. Then, 0.1 mL of respective microorganism in sterile saline was injected in each test tube and then incubated at 37 °C for 24 h. Results were recorded visually in terms of Minimum Inhibitory Concentration (MIC) in µmol/mL.
3 Results and Discussion
3.1 Chemistry
The synthetic pathways adopted for the synthesis of benzothiazole and benzoxazole containing triazoles (7a-7t) have been presented in Scheme 1. The terminal alkynes viz., 2-(prop-2-yn-1-ylthio)benzooxazol e(3a)/2-(prop-2-yn-1-ylthio)benzothiazole (3b) were obtained from the propargylation of 2-mercaptobenzoxazole (1a)/2-mercaptobenzothiazole (1b) in DMF with propargyl bromide (2) in the presence of potassium carbonate.
Synthesis of benzothiazole and benzoxazole linked 1,4-disubstituted 1,2,3-triazoles.
4-(Bromomethyl)-N-arylbenzamide (6a-6j) were synthesized by reaction of 4-(bromomethyl)benzoylbromide (4) and aromatic amines (5a-5j) by using potassium carbonate.
Finally, 4-(bromomethyl)-N-arylbenzamide derivatives (6a-6j) and 2-(prop-2-yn-1-ylthio)benzooxazole (3a)/2-(prop-2-yn-1-ylthio)benzothiazole (3b) were dissolved in DMF followed by addition of aqueous sodium azide, a catalytic amount of copper sulphate pentahydrate, sodium ascorbate and continued stirring for 6-10 h at 25-40 °C to obtain targeted 1,4-disubstituted 1,2,3-triazoles (7a-7t).
The structures of synthesized triazoles (7a–7t) were confirmed by FTIR, 1H NMR, 13C NMR spectroscopy and HRMS. In FTIR spectra of all the compounds characteristic absorption band due to C–H stretching of triazole ring observed at 3199–3107 cm−1, N–H stretching of amide linkages at 3365–3257 cm−1 and 1660–1643 cm−1 were due to C=O stretching of amide bonds. The 1H NMR spectra of all the compounds exhibited characteristic singlet due to N–H proton in the range of δ 10.07-10.77. A singlet in a range of δ 8.22-8.29 was assigned to triazolyl proton. Two singlets in the range of δ 4.65-4.71 and δ 5.63-5.71 in the 1H-NMR spectra assigned to -SCH2 and -NCH2, respectively.
In 13C-NMR spectral data, a characteristic signal of carbon of C=O of amide appeared in the range of δ 166.14-165.31. C–4 and C–5 signals corresponding to triazole ring appeared at δ 143.00–143.30 and δ 124.62–124.93, respectively. A signal in the range of δ 26.90-27.94 appeared due to carbon attached to sulphur and a signal in the range of δ 52.91-52.98 due to methylene carbon attached to nitrogen of triazole. The final confirmation was made by the HRMS analysis which showed the presence of [M+H]+ ion peaks.
3.2 Antibacterial activity
All the synthesized 1,2,3-triazoles were screened for antibacterial activities of against two Gram-positive bacteria S. aureus, B. subtilis, two Gram-negative bacteria E. coli and K. pneumoniae via serial dilution method. Ciprofloxacin was used as a standard against both Gram-positive and Gram-negative bacteria. The MIC values of synthesized compounds are presented in Table 1.
It has been observed that in most of the cases the presence of any substituent on benzene ring led to increased activity towards all the tested bacterial strain. Further, the presence of electron-withdrawing group showed an advantage over an electron-donating group on the benzene ring. The compounds 7f, 7p with a nitro group showed enhanced activity than its unsubstituted or alkyl-substituted analogs. 1,2,3-triazoles containing methyl group at meta position (7c, 7m), showed better activity than its ortho or para counterparts. Compounds 7i, 7s containing bromo group on benzene ring exhibited better activity in comparison with fluoro and chloro substituents. Compounds 7j and 7t with naphthyl ring displayed potential activity against all the tested bacterial strains. All the triazole derivatives containing benzothiazole ring exhibited better efficacy as compared to the benzoxazole ring.
4 Conclusions
In the present case, we have synthesized a new promising class of benzothiazole-triazole and benzoxazole-triazole hybrids (7a-7t) through click reaction in good yields by reacting 2-(prop-2-yn-1-ylthio)benzooxazole (3a)/2-(prop-2-yn-1-ylthio)benzothiazole (3b) with appropriate 4-(bromomethyl)-N-arylbenzamides (6a-6j) and sodium azide. The synthesized disubstituted-1,2,3-triazoles reflected encouraging antibacterial activity. However, compound 7s exhibited promising antibacterial activity comparable with standard drug Ciprofloxacin.
Abbreviations
- MIC:
-
Minimum Inhibitory Concentration
- MTCC:
-
Microbial Type Culture Concentration
- NCDC:
-
National Collection of Dairy Culture
References
Singh G, Chowdhary K, Satija P, Singh A, Singh B, Singh K, Espinosa C B, Esteban M A, Sehgal R and Verma V 2018 Synthesis and immobilization of benzothiazole-appended triazole-silane: Biological evaluation and molecular docking approach Chem. Select 3 1609
Kumbhare R M, Dadmal T, Kosurkar U, Sridhar V and Rao J V 2012 Synthesis and cytotoxic evaluation of thiourea and N-bis-benzothiazole derivatives: A novel class of cytotoxic agents Bioorg. Med. Chem. Lett. 22 453
Aouad M R, Soliman M A, Alharbi M O, Bardaweel S K, Sahu P K, Ali A A, Messali M, Rezki N and Soud Y A A 2018 Design, synthesis and anticancer screening of novel benzothiazole-piperazine-1,2,3-triazole hybrids Molecules 23 2788
Santhoshi A and Alam H 2014 Synthesis of thio-pyrimidine, benzoxazole, benzothiazole and triazole analogues from Baylis-Hillman Bromides as potent cyclooxygenase-2 inhibitors J. Chem. Pharm. Sci. 2014 Special Issue
Chandramouli, Shivanand M R, Nayanbhai T B, Bheemachari and Udupi R H 2012 Synthesis and biological screening of certain new triazole schiff bases and their derivatives bearing substituted benzothiazole moiety J. Chem. Pharm. Res. 4 1151
Faraji L, Shahkarami S, Nadri H, Moradi A, Saeedi M, Foroumadi A, Ramazani A, Haririan I, Ganjali M R, Shafiee A and Khoobi M 2017 Synthesis of novel benzimidazole and benzothiazole derivatives bearing a 1,2,3-triazole ring system and their acetylcholinesterase inhibitory activity J. Chem. Res. 41 30
Raju K S, Reddy S A, Sabitha G, Krishna V S, Sriram D, Reddy K B and Sagurthi S R 2019 Synthesis and biological evaluation of 1H-pyrrolo[2,3-d]pyrimidine-1,2,3-triazole derivatives as novel anti-tubercular agents Bioorg. Med. Chem. Lett. 29 284
Li H, Wang H, Wang Z, Yan H, Zhang M, Liu Y and Cheng M 2018 Synthesis, antitumor activity evaluation and mechanistic study of novel hederacolchiside A1 derivatives bearing an aryl triazole moiety Bioorg. Med. Chem. 26 4025
Gilandoust M, Harsha K B, Mohan C D, Raquib A R, Rangappa S, Pandey V, Lobie P E, Basappa and Rangappa K S 2018 Synthesis, characterization and cytotoxicity studies of 1,2,3-triazoles and 1, 2,4-triazolo [1,5-a] pyrimidines in human breast cancer cells Bioorg. Med. Chem. Lett. 28 2314
Shankaraiah N, Kumar N P, Tokala R, Gayatri B S, Talla V and Santos L S 2019 Synthesis of new 1,2,3-triazolo-naphthalimide/phthalimide conjugates via ‘click’ reaction: DNA intercalation and cytotoxic studies J. Braz. Chem. Soc. 30 454
Lu G Q, Li X Y, Mohamed O K, Wang D and Meng F H 2019 Design, synthesis and biological evaluation of novel uracil derivatives bearing 1, 2, 3-triazole moiety as thymidylate synthase (TS) inhibitors and as potential antitumor drugs Eur. J. Med. Chem. 171 282
Pasupuleti B G, Khongsti K, Das B and Bez G 2020 1, 2, 3-Triazole tethered 1, 2, 4-trioxanes: Studies on their synthesis and effect on osteopontin expression in MDA-MB-435 breast cancer cells Eur. J. Med. Chem. 186 111908
Shinoda K, Kanai M and Sohma Y 2020 Design, synthesis, and properties of a chemically-tethered amyloid-β segment trimer resistant to inter-trimer mis-aggregation J. Org. Chem. 85 1635
Zimmermann L A, Moraes M H, Rosa R, Melo E B, Paula F R, Schenkela E P Steindel, M and Bernardes L S C 2018 Synthesis and SAR of new isoxazole-triazole bis-heterocyclic compounds as analogues of natural lignans with antiparasitic activity Bioorg. Med. Chem. 26 4850
Tan W, Li Q, Dong F, Zhanga J, Luana F, Wei L, Chena Y and Guo Z 2018 Novel cationic chitosan derivative bearing 1,2,3-triazolium and pyridinium: Synthesis, characterization, and antifungal property Carbohydr. Polym. 182 180
Govindaiah S, Sreenivasa S, Ramakrishna R A, Rao T M C and Nagabhushana H 2018 Regioselective synthesis, antibacterial, molecular docking and fingerprint applications of 1-benzhydrylpiperazine derivatized 1,4-disubstituted 1,2,3-triazoles Chem. Select 3 8111
Zhou J, Stapleton P, Haider S and Healy J 2018 Boronic acid inhibitors of the class A b-lactamase KPC-2 Bioorg. Med. Chem. 26 2921
Abbaspour S, Keivanloo A, Bakherad M and Sepehri S 2019 Salophen copper(II) complex-assisted click reactions for fast synthesis of 1,2,3-triazoles based on naphthalene-1,4-dione scaffold, antibacterial evaluation, and molecular docking studies Chem. Biodivers. 16 e1800410
Kaushik C P, Luxmi R, Kumar A, Kumar K and Pahwa A 2019 Antibacterial evaluation and QSAR studies of 1,2,3-triazole bridged with amide functionality Indian J. Chem. 58B 88
Torres L M F C, Almeida M T, Santos T L, Marinho L E S, Mesquita J P, Silva L M, Santos W T P, Martins H R, Kato K C, Alves E S F, Liao L M, Magalhaes M T Q, Mendonça F G, Pereira F V, Resende J M, Bemquerer M P, Rodrigues M A and Verly R M 2019 Antimicrobial alumina nanobiostructures of disulfide- and triazole-linked peptides: Synthesis, characterization, membrane interactions and biological activity Colloids Surf. B 177 94
Bommagani M B, Mokenapelli S, Yerrabelli J R, Boda S K and Chitneni P R 2020 Novel 4-(1H-1, 2, 3-triazol-4-yl) methoxy) cinnolines as potent antibacterial agents: Synthesis and molecular docking study Synth. Commun. 50 1016
Deswal S, Naveen, Tittal R K, Vikas D G, Lal K and Kumar A 2020 5-Fluoro-1H-indole-2, 3-dione-triazoles-synthesis, biological activity, molecular docking, and DFT study J. Mol. Struct. 1209 127982
Gontijo V S, Espuri P F, Alves R B, Camargos L F, Santos F V, Alves W, Marques M and Freitas R 2015 Leishmanicial, antiproteolytic, and mutagenic evaluation of alkyltriazoles and alkylphosphocholines Eur. J. Med. Chem. 101 24
Bonache M A, Fernandez S M, Miguel M, Munoz B S and Muniz R G 2018 Small library of triazolyl polyphenols correlating antioxidant activity and stability with number and position of hydroxyl groups ACS Comb. Sci. 20 694
Kaushik C P and Luxmi R 2020 Synthesis, antibacterial, and antioxidant activities of naphthyl‐linked disubstituted 1,2,3‐triazoles J. Het. Chem. 57 2400
Kumar A K, Sunitha V, Shankar B, Ramesh M, Krishna T M and Jalapathi P 2016 Synthesis, Biological Evaluation, and Molecular Docking Studies of Novel 1,2,3-Triazole Derivatives as Potent Anti-Inflammatory Agents Russ. J. Gen. Chem. 86 1154
Maurent K, Bacque C V, Baltas M, Salvayre A N, Auge N and Belval F B 2018 Synthesis and biological evaluation of diarylheptanoids as potential antioxidant and anti-inflammatory agents Eur. J. Med. Chem. 144 289
Litchfield M, Wuest M, Glubrecht D and Wues F 2020 Radiosynthesis and Biological Evaluation of [18F] Triacoxib: A New Radiotracer for PET Imaging of COX-2 Mol. Pharm. 17 251
Sahu A, Das D, Sahu P, Mishra S, Sakthivel A, Gajbhiye A and Agrawal R 2020 Bioisosteric replacement of amide group with 1,2,3-triazoles in acetaminophen addresses reactive oxygen species-mediated hepatotoxic insult in Wistar albino rats Chem. Res. Toxicol. 33 522
Devender N, Gunjan S, Tripathi R and Tripathi R P 2017 Synthesis and antiplasmodial activity of novel indoleamide derivatives bearing sulfonamide and triazole pharmacophores Eur. J. Med. Chem. 131 171
Wang G, Peng Z, Wang J, Li X and Li J 2017 Synthesis, in vitro evaluation and molecular docking studies of novel triazine-triazole derivatives as potent α-glycosidase inhibitors Eur. J. Med. Chem. 125 423
Tian Y, Liu Z, Liu J, Huang B, Kang D, Zhang H, Clercq E D, Daelemans D, Pannecouque C, Lee K H Chen C H Zhan P and Liu X 2018 Targeting the entrance channel of NNIBP: Discovery of diarylnicotinamide 1,4-disubstituted 1,2,3-triazoles as novel HIV-1 NNRTIs with high potency against wildtype and E138K mutant virus Eur. J. Med. Chem. 151 339
Tantray M A, Khan I, Hamid H, Alam M S, Dhulap A and Kalam A 2016 Synthesis of benzimidazole-based 1,3,4-oxadiazole-1,2,3-triazole conjugates as glycogen synthase kinase-3β inhibitors with antidepressant activity in in vivo models RSC Adv. 6 43345
Bagheri S M, Khoobi M, Nadri H, Moradi A, Emami S, Baleh L J, Jafarpour F, Moghadam F H, Foroumadi A and Shafie A 2015 Synthesis and anticholinergic activity of 4-hydroxycoumarin derivatives containing substituted benzyl-1,2,3-triazole moiety Chem. Biol. Drug Des. 86 1215
Fatih C, Yasemin U, Burak B, Arzu O and Kemal S 2018 Synthesis, characterization and biological activities of new symmetric bis-1,2,3-triazoles with click chemistry Med. Chem. 14 230
Shafi S, Alam M M, Mulakayala N, Mulakayala C, Vanaja G, Kalle A M, Pallu R and Alam M S 2012 Synthesis of novel 2-mercapto benzothiazole and 1,2,3-triazole based bis-heterocycles: Their anti-inflammatory and anti-nociceptive activities Eur. J. Med. Chem. 49 324
Haider S, Alam M S, Hamid H, Shafi S, Dhulap A, Hussain F, Alam P, Umar S, Pasha M A Q, Bano S, Nazreen S, Ali Y and Kharbanda C 2014 Synthesis of novel 2-mercaptobenzoxazole based 1,2,3-triazoles as inhibitors of proinflammatory cytokines and suppressors of COX-2 gene expression Eur. J. Med. Chem. 81 204
Kaushik C P, Pahwa A, Singh D, Kumar K and Luxmi R 2019 Efficient synthesis, antitubercular and antimicrobial evaluation of 1, 4-disubstituted 1, 2, 3-triazoles with amide functionality Montash. Chem. 150 1127
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Kaushik, C.P., Chahal, M. Synthesis and antibacterial activity of benzothiazole and benzoxazole-appended substituted 1,2,3-triazoles. J Chem Sci 132, 142 (2020). https://doi.org/10.1007/s12039-020-01844-8
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DOI: https://doi.org/10.1007/s12039-020-01844-8