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Synthesis and antimicrobial activities of some novel thiazole compounds

  • Gülhan Turan-Zitouni , Betül Kaya Çavuşoğlu EMAIL logo , Begüm Nurpelin Sağlık and Ulviye Acar Çevik
Published/Copyright: November 28, 2017
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Turkish Journal of Biochemistry
From the journal Turkish Journal of Biochemistry Volume 43 Issue 3

Abstract

Objective

The advent of resistant pathogenic microorganisms against current antimicrobial drugs prompted scientists to investigate novel molecules with new mechanisms. In this paper, some new 2-[2-[4-(ethyl/phenyl)cyclohexylidene]hydrazinyl]-4-(4-substitutedphenyl)thiazole (2a–2o) derivatives were synthesized and studied for their antimicrobial activities.

Materials and methods

The title compounds (2a–2o) were obtained via the reaction of 4-(ethyl/phenyl)cyclohexane-1-one with appropriate phenacyl bromide in ethanol at room temperature. The chemical structures of the compounds were elucidated by FT-IR, 1H-NMR, 13C-NMR, HRMS and elemental analysis. Antimicrobial activity of the compounds was measured by using broth microdilution method. Chloramphenicol and ketoconazole were used as reference drugs.

Results

Among the synthesized compounds, 2-[2-(4-phenylcyclohexylidene)hydrazinyl]-4-phenylthiazole (2h) and 2-[2-(4-phenylcyclohexylidene)hydrazinyl]-4-(4-chlorophenyl)thiazole (2l) have been found to exhibit potency almost four-fold better than ketoconazole against C. albicans with MIC90 value of 1.95.

Conclusion

The current study contributed to the knowledge of the antimicrobial activity of thiazole bearing compounds.

Özet

Amaç

Mevcut antimikrobiyal ilaçlara karşı dirençli patojen mikroorganizmaların ortaya çıkışı bilim insanlarını farklı mekanizmalara sahip yeni molekülleri keşfetmeye sevk etmiştir. Bu çalışmada, bazı yeni 2-[2-[4-(etil/fenil)sikloheksiliden]hidrazinil]-4-(4-sübstitüefenil)tiyazol (2a–2o) türevleri sentezlenmiş ve antimikrobiyal etkileri araştırılmıştır.

Metot

Final bileşikleri (2a–2o) 4-(etil/fenil)sikloheksan-l-on ile uygun fenaçil bromürlerin oda ısısında etanol içinde reaksiyona sokulmasıyla elde edilmiştir. Bileşiklerin kimyasal yapıları FT-IR, 1H-NMR, 13C-NMR, HRMS spektrum verileri ve elementel analiz kullanılarak aydınlatılmıştır. Antimikrobiyal aktivite çalışmaları broth mikrodilüsyon yöntemi ile tespit edilmiştir. Kloramfenikol ve ketokonazol referans ilaç olarak kullanılmıştır.

Bulgular

Sentezlenen bileşikler arasında, 2-[2-(4-fenilsikloheksiliden)hidrazinil]-4-feniltiyazol (2h) ve 2-[2-(4-fenilsiklohekziliden)hidrazinil]-4-(4-klorofenil)tiyazol (2l) türevlerinin 1.95 MIC90 değeri ile C. albicans’a karşı ketokonazolden yaklaşık dört kat daha etkili olduğu tespit edilmiştir.

Sonuç

Bu çalışma tiyazol taşıyan bileşiklerin antimikrobiyal etki gösterdiğini desteklemiştir.

Keywords: Antibacterial activity; Antifungal activity; Thiazole; Broth microdilution method
Anahtar Kelimeler: Antibakteriyel aktivite; Antifungal aktivite; Tiyazol; Broth mikrodilüsyon yöntemi

Introduction

One of the most significant current discussions in the world is the therapy of infectious diseases due to the increasing appearance of resistant pathogenic microorganisms against present antibacterial and antifungal drugs [1], [2]. Recent research, thus, has tended to focus on developing new effective antimicrobial agents that act through different mechanisms than the conventional drugs, particularly for the treatment of the infections of hospitalized and immunosuppressed patients [3]. Therefore, the disclosure of novel and powerful antibacterial and antifungal drugs is very necessary.

Considering antimicrobial agents with innovative mode of actions, various heterocyclic rings have attracted a great interest over the years owing to their different biological activities. Among diverse heterocyclic compounds, thiazoles and their derivatives are crucial scaffolds in medicinal chemistry. In many pharmaceutically active compounds and natural products such as including thiamin and penicillin G, thiazole ring composes the scaffold of core molecular structure. Thiazole compounds are accompanied with improved lipophilicity and are metabolized via known biochemical reactions [4]. The enthusiasm for thiazoles is because of their potential natural action and magical physicochemical characteristics thus, some many potent drugs such as sulfathiazole (antimicrobial drug) and abafungin (antifungal drug) contain a thiazole ring. Thiazole and its derivatives are important pharmacophore and they have a broad range of biological activities including antimicrobial [5], [6], [7], [8], [9], [10], antitumor [11], [12], anti-inflammatory [13], anti-cancer [14], anti-tubercular [15], [16], antiviral [17], antioxidant [18], anti HIV [19], antihypertensive [20], antischizophrenia [21], antiallergic [22] and analgesic activity [23]. Besides that, it was clear that thiazoles have gotten significant consideration because of their effective properties as antimicrobial agents.

Based on the above-mentioned findings to recognize new candidates that may be with a great value in designing new, potent and selective antimicrobial agents, we report in this paper the synthesis and antimicrobial activity of some new thiazole derivatives.

Materials and methods

Chemicals

All chemicals were purchased from Sigma-Aldrich Chemicals (Sigma-Aldrich Corp., St. Louis, MO, USA) and Merck Chemicals (Merck KGaA, Darmstadt, Germany). All melting points (m.p.) were determined by MP90 digital melting point apparatus (Mettler Toledo, OH, USA) and were uncorrected. All reactions were monitored by thin-layer chromatography (TLC) using Silica Gel 60 F254 TLC plates (Merck KGaA, Darmstadt, Germany). Spectroscopic data were recorded with the following instruments: IR, Shimadzu Affinity 1S spectrophotometer (Shimadzu, Tokyo, Japan); NMR, Bruker DPX 500 NMR spectrometer (Bruker Bioscience, Billerica, MA), in DMSO-d6, using TMS as internal standard; M+1 peaks were determined by Shimadzu LC/MS ITTOF system (Shimadzu, Tokyo, Japan). Elemental analyses were performed on a Perkin-Elmer EAL 240 elemental analyser (Perkin-Elmer, Norwalk, USA).

General procedure for synthesis of the compounds

General procedure for the synthesis of 2-[4-(ethyl/phenyl)cyclohexylidene]hydrazine-1-carbothioamide derivatives (1a, 1b)

4-(Ethyl/phenyl)cyclohexane-1-one (29 mmol) was dissolved in ethanol (100 mL). Thiosemicarbazide (29 mmol) and a catalytic amount of acetic acid were added and the reaction mixture was refluxed for 2 h. After completion of reaction, the mixture was cooled, precipitated product was filtered and recrystallized from ethanol [24], [25].

General procedure for the synthesis of 4-(4-substitutedphenyl)-2-[2-[4-(ethyl/phenyl) cyclohexylidene]hydrazinyl]thiazole (2a–2o)

Compounds 1a or 1b (2 mmol) and appropriate phenacyl bromide (2 mmol) were dissolved in ethanol (25 mL). The reaction mixture stirred at room temperature for 1–8 h. After TLC screening, precipitated product was filtered and recrystallized from ethanol.

2-[2-(4-Ethylcyclohexylidene)hydrazinyl]-4-(p-methylphenyl)thiazole (2a) Yield 65%. m.p. 187°C. IR (KBr, cm−1): ʋmax 3309 (N–H stretching), 3105–3017 (aromatic C–H), 2953–2842 (aliphatic C–H), 1602–1445 (C=N and C=C stretching). 1H-NMR (500 MHz, DMSO-d6, ppm) δ 0.91 (t, 3H, CH3), 1.03–1.43 (m, 5H, CH2, cyclohexyl-H), 1.88–1.95 (m, 3H, cyclohexyl-H), 2.16–2.35 (m, 3H, cyclohexyl-H), 2.31 (s, 3H, CH3), 7.22 (d, J=8.3 Hz, 2H, Ar-H), 7.31 (s, 1H, thiazole-H), 7.71 (d, J=8.3 Hz, 2H, Ar-H), 8.20 (1H, s, NH). 13C-NMR (125 MHz, DMSO-d6, ppm) δ 11.97 (CH3), 21.26 (CH3), 26.82, 31.64, 32.21, 32.82, 34.37, 37.28 (CH2), 105.2 (CH-thiazole), 125.98, 126.23, 129.08, 129.61 (CH), 129.98, 130.2 (C ), 149.1 (C ), 153.20(C=N). For C18H23N3S calculated: 68.97% C, 7.40% H, 13.41% N, 10.23% S; found: 69.12% C, 7.38% H, 13.43% N, 10.21% S. HRMS (m/z): [M+H]+ calcd for C18H23N3S: 314.1685; found 314.1685.

2-[2-(4-Ethylcyclohexylidene)hydrazinyl]-4-(4-methoxyphenyl)thiazole (2b) Yield 64%. m.p. 187°C. IR (KBr, cm−1): ʋmax 3324 (N–H stretching), 3105–3017 (aromatic C–H), 2953–2842 (aliphatic C–H), 1608–1455 (C=N and C=C stretching). 1H-NMR (500 MHz, DMSO-d6, ppm) δ 0.89 (t, 3H, CH3), 1.05–1.43 (m, 5H, CH2, cyclohexyl-H), 1.88–2.37 (m, 6H, cyclohexyl-H), 3.78 (s, 3H, OCH3), 6.97 (d, J=9.1 Hz, 2H, Ar-H), 7.07 (s, 1H, thiazole-H), 7.76 (d, J=8.5 Hz, 2H, Ar-H), 10.75 (s, 1H, NH). 13C-NMR (100 MHz, DMSO-d6, ppm) δ 11.97 (CH3), 26.82, 28.67, 31.64, 32.83, 34.37, 38.13, 39.66 (CH2), 55.60 (OCH3), 114.42, 114.90, 127.38 (CH). For C18H23N3OS calculated: 65.62% C, 7.04% H, 12.75% N, 4.86% O, 9.73% S; found: 65.72% C, 7.02% H, 12.77% N, 4.85% O, 9.74% S. HRMS (m/z): [M+H]+ calcd for C18H23N3OS: 330.1635; found 330.1641.

2-[2-(4-Ethylcyclohexylidene)hydrazinyl]-4-(4-bromophenyl)thiazole (2c) Yield 68%. m.p. 204°C. IR (KBr, cm−1): ʋmax 3307 (N–H stretching), 3087-3004 (aromatic C–H), 2951–2856 (aliphatic C–H), 1604–1481 (C=N and C=C stretching). 1H-NMR (500 MHz, DMSO-d6, ppm) δ 0.90 (t, 3H, CH3), 1.24–1.34 (m, 5H, CH2, cyclohexyl-H), 1.59–2.35 (m, 6H, cyclohexyl-H), 7.64–7.70 (m, 4H, Ar-H), 8.35 (s, 1H, thiazole-H), 10.89 (s, 1H, NH). 13C-NMR (100 MHz, DMSO-d6, ppm) δ 11.85 (CH3), 12.13 (CH2), 28.11, 29.57, 32.22, 34.33, 37.28 (CH2), 38.23 (CH), 117.85 (CH-thiazole), 128.33, 128.50, 128.64, 132.18 (CH), 132.37, 132.28, 153.44, 175.58 (C). For C17H20BrN3S calculated: 53.97% C, 5.33% H, 21.12% Br, 11.11% N, 8.48% S; found: 53.81% C, 5.31% H, 21.17% Br, 11.09% N, 8.47% S. HRMS (m/z): [M+H]+ calcd for C17H20BrN3S: 378.0634; found 378.0630.

2-[2-(4-Ethylcyclohexylidene)hydrazinyl]-4-(4-chlorophenyl)thiazole (2d) Yield 66%. m.p. 189°C IR (KBr, cm−1): ʋmax 3304 (N–H stretching), 3098–3006 (aromatic C–H), 2995–2872 (aliphatic C–H), 1604–1487 (C=N and C=C stretching). 1H-NMR (500 MHz, DMSO-d6, ppm) δ 0.91 (t, 3H, CH3), 1.24–1.29 (m, 3H, CH2, cyclohexyl-H), 1.58–2.32 (m, 8H, cyclohexyl-H), 7.59 (d, J=8.6 Hz, 2H, Ar-H), 8.03 (d, J=8.5 Hz, 2H, Ar-H), 8.34 (s, 1H, thiazole-H), 10.97 (s, 1H, NH). 13C-NMR (100 MHz, DMSO-d6, ppm) δ 11.85 (CH3), 12.13 (CH2), 28.11, 29.57, 32.22, 34.33, 37.28 (CH2), 38.23 (CH), 117.78 (CH-thiazole), 128.05, 129.46, 132.94 (CH), 133.55, 175.58 (C). For C17H20ClN3S calculated: 61.15% C, 6.04% H, 10.62% Cl, 12.59% N, 9.60% S; found: 61.28% C, 6.05% H, 10.64% Cl, 12.56% N, 9.61% S. HRMS (m/z): [M+H]+ calcd for C17H20ClN3S: 334.1139; found 334.1130.

2-[2-(4-Ethylcyclohexylidene)hydrazinyl]-4-(4-fluorophenyl)thiazole (2e) Yield 68%. m.p. 195°C. IR (KBr, cm−1): ʋmax 3318 (N–H stretching), 3108–3028 (aromatic C–H), 2958–2842 (aliphatic C–H), 1624–1487 (C=N and C=C stretching). 1H-NMR (500 MHz, DMSO-d6, ppm) δ 0.90 (t, 3H, CH3), 1.01-1.39 (m, 5H, CH2, cyclohexyl-H), 1.85–1.93 (m, 3H, cyclohexyl-H), 2.18–2.34 (m, 3H, cyclohexyl-H), 7.21–7.25 (m, 3H, Ar-H), 7.86–7.89 (m, 2H, Ar-H), 10.84 (s, 1H, NH). 13C-NMR (100 MHz, DMSO-d6, ppm) δ 11.97 (CH3), 26.74 (CH), 28.69 (CH), 31.63, 32.84, 34.40, 37.19 (CH2), 103.35, 115.74 (CH-thiazole), 115.92, 127.86, 127.92, 132.02 (CH) 155.86, 160.99, 162.93, 170.66 (C). For C17H20FN3S calculated: 64.32% C, 6.35% H, 5.99% F, 13.24% N, 10.10% S; found: 64.45% C, 6.36% H, 5.97% F, 13.26% N, 10.12% S. HRMS (m/z): [M+H]+ calcd for C17H20FN3S: 318.1435; found 318.1457.

2-[2-(4-Ethylcyclohexylidene)hydrazinyl]-4-(4-nitrophenyl)thiazole (2f) Yield 70%. m.p. 181°C. IR (KBr, cm−1): ʋmax 3311 (N–H stretching), 3078–3013 (aromatic C–H), 2997–2858 (aliphatic C–H), 1612–1479 (C=N and C=C stretching). 1H-NMR (500 MHz, DMSO-d6, ppm) δ 0.87–0.92 (m, 3H, CH3), 1.05–2.33 (m, 8H, CH2, cyclohexyl-H), 2.03–3.01 (m, 3H, cyclohexyl-H), 8.09–8.34 (m, 4H, Ar-H), 8.62 (s, 1H, thiazole-H), 10.97 (s, 1H, NH). 13C-NMR (125 MHz, DMSO-d6, ppm) δ 11.85 (CH3), 12.13 (CH2), 26.81, 28.20, 31.63, 34.39, 38.08 (CH2), 108.62 (CH-thiazole), 121.16, 124.14, 126.74, 129.18, 129.55 (CH), 146.55, 147.50, 170.96 (C). For C17H20N4O2S calculated: 59.28% C, 5.85% H, 16.27% N, 9.29% O, 9.31% S; found: 59.36% C, 5.84% H, 16.30% N, 9.31% O, 9.32% S. HRMS (m/z): [M+H]+ calcd for C17H20N4O2S: 345.1380; found 345.1373.

2-[2-(4-Ethylcyclohexylidene)hydrazinyl]-4-(4-cyanophenyl)thiazole (2g) Yield 69%. m.p. 187°C. IR (KBr, cm−1): ʋmax 3317 (N–H stretching), 3095–3025 (aromatic C–H), 2984–2858 (aliphatic C–H), 2358 (C≡N stretching), 1600–1435 (C=N and C=C stretching). 1H-NMR (500 MHz, DMSO-d6, ppm) δ 0.90 (t, 3H, CH3), 1.26–1.32 (m, 5H, CH2, cyclohexyl-H), 1.60–2.35 (m, 6H, cyclohexyl-H), 7.99 (d, J=8.3 Hz, 2H, Ar-H), 8.21 (d, J=8.4 Hz, 2H, Ar-H), 8.55 (s, 1H, thiazole-H), 10.71 (s, 1H, NH). 13C-NMR (100 MHz, DMSO-d6, ppm) δ 11.85 (CH3), 12.13 (CH2), 28.09, 32.21, 34.31, 37.28, 38.22 (CH2), 96.62 (CH), 112.22 (C), 119.23 (CN), 120.41, 126.98, 127.32, 133.13 (CH), 133.49, 179.5 (C), 138.16. For C18H20N4S calculated: 66.64% C, 6.21% H, 17.27% N, 9.88% S; found: 66.45% C, 6.22% H, 17.29% N, 9.85% S. HRMS (m/z): [M+H]+ calcd for C18H20N4S: 325.1481; found 325.1488.

2-[2-(4-Phenylcyclohexylidene)hydrazinyl]-4-phenylthiazole (2h) Yield 75%. m.p. 199°C. IR (KBr, cm−1): ʋmax 3381 (N–H stretching), 3061–3007 (aromatic C–H), 2920–2856 (aliphatic C–H), 1608–1444 (C=N and C=C stretching). 1H-NMR (500 MHz, DMSO-d6, ppm) δ 1.57–1.73 (m, 2H, cyclohexyl-H), 1.94–2.01 (m, 2H, cyclohexyl-H), 2.05–2.08 (m, 1H, cyclohexyl-H), 2.39–2.45 (m, 2H, cyclohexyl-H), 2.85 (t, 1H, cyclohexyl-H), 3.18 (d, 1H, cyclohexyl-H), 7.20 (t, J=6.8 Hz, 1H, Ar-H), 7.87 (s, 1H, Ar-H), 7.26–7.31 (m, 5H, Ar-H), 7.41 (t, 2H, Ar-H), 7.85 (d, J=7.5 Hz, 2H, Ar-H), 10.97 (br s, 1H, NH). 13C-NMR (125 MHz, DMSO-d6, ppm) δ 27.38, 33.19, 34.45, 35.02 (CH2), 43.03 (CH), 126.00, 126.57, 127.20, 127.93, 128.83, 129.04 (CH), 146.37, 170.54 (C). For C21H21N3S calculated: 72.59% C, 6.09% H, 12.09% N, 9.23% S; found: 72.80% C, 6.07% H, 12.10% N, 9.24% S. HRMS (m/z): [M+H]+ calcd for C21H21N3S: 348.1529; found 348.1546.

2-[2-(4-Phenylcyclohexylidene)hydrazinyl]-4-(p-methylphenyl)thiazole (2i) Yield 69%. m.p. 202°C. IR (KBr, cm−1): ʋmax 3334 (N–H stretching), 3116–3021 (aromatic C–H), 2972–2853 (aliphatic C–H), 1606–1457 (C=N and C=C stretching). 1H-NMR (500 MHz, DMSO-d6, ppm) δ 1.58–1.74 (m, 2H, cyclohexyl-H), 1.96–2.03 (m, 2H, cyclohexyl-H), 2.40–2.45 (m, 4H, cyclohexyl-H), 2.35 (s, 3H, CH3), 2.86 (t, 1H, cyclohexyl-H), 7.18–7.33 (m, 9H, Ar-H), 7.73 (d, J=8.1 Hz, 1H, Ar-H), 11.09 (s, 1H, NH). 13C-NMR (125 MHz, DMSO-d6, ppm) δ 21.26 (CH3), 27.43, 33.18, 33.82, 34.43, 34.99, 37.62 (CH2), 42.99 (CH), 126.00, 126.25, 126.58, 126.69, 127.19, 128.69, 128.84, 129.62, 129.99 (CH), 137.34, 146.34 (C), 170.42 (C–N). For C22H23N3S calculated: 73.09% C, 6.41% H, 11.62% N, 8.87% S; found: 73.26% C, 6.42% H, 11.65% N, 8.89% S. HRMS (m/z): [M+H]+ calcd for C22H23N3S: 362.1685; found 362.1711.

2-[2-(4-Phenylcyclohexylidene)hydrazinyl]-4-(4-methoxyphenyl)thiazole (2j) [26]

2-[2-(4-Phenylcyclohexylidene)hydrazinyl]-4-(4-bromophenyl)thiazole (2k) Yield 65%. m.p. 207°C. IR (KBr, cm−1): ʋmax 3309 (N–H stretching), 3105–3024 (aromatic C–H), 2972–2869 (aliphatic C–H), 1610–1479 (C=N and C=C stretching). 1H-NMR (500 MHz, DMSO-d6, ppm) δ 1.59–1.72 (m, 2H, cyclohexyl-H), 1.91–2.11 (m, 3H, cyclohexyl-H), 2.38–2.48 (m, 2H, cyclohexyl-H), 2.85–2.87 (m, 1H, cyclohexyl-H), 3.17–3.19 (m, 1H, cyclohexyl-H), 7.18–7.32 (m, 6H, Ar-H), 7.52–7.80 (m, 4H, Ar-H), 10.99 (s, 1H, NH). 13C-NMR (125 MHz, DMSO-d6, ppm) δ 27.37, 33.17, 33.82, 34.44 (CH), 34.67 (C), 104.65 (CH-thiazole), 120.85 (C), 126.57, 128.02, 130.27, 132.39 (CH), 146.35, 170.67 (C). For C21H20BrN3S calculated: 59.16% C, 4.73% H, 18.74% Br, 9.86% N, 7.52% S; found: 59.25% C, 4.73% H, 18.70% Br, 9.88% N, 7.50% S. HRMS (m/z): [M+H]+ calcd for C21H20BrN3S: 426.0634; found 426.0631.

2-[2-(4-Phenylcyclohexylidene)hydrazinyl]-4-(4-chlorophenyl)thiazole (2l) Yield 70%. m.p. 175°C. IR (KBr, cm−1): ʋmax 3336 (N–H stretching), 3116–3012 (aromatic C–H), 2927–2841 (aliphatic C–H), 1635–1485 (C=N and C=C stretching). 1H-NMR (500 MHz, DMSO-d6, ppm) δ 1.57–1.72 (m, 3H, cyclohexyl-H), 1.91–2.01 (m, 1H, cyclohexyl-H), 2.04–2.09 (m, 2H, cyclohexyl-H), 2.37–2.44 (m, 1H, cyclohexyl-H), 2.85–2.88 (m, 1H, cyclohexyl-H), 3.17–3.19 (m, 1H, cyclohexyl-H), 7.20–7.23 (m, 1H, Ar-H), 7.27–7.32 (m, 5H, Ar-H), 7.45 (d, J=8.30 Hz, 2H, Ar-H), 7.88 (d, J=8.45 Hz, 2H, Ar-H), 10.98 (br s, 1H, NH). 13C-NMR (125 MHz, DMSO-d6, ppm) δ 27.36, 33.17, 34.44, 37.21 (CH2), 43.02 (CH), 104.54 (CH-thiazole), 126.57, 127.20, 127.69, 128.83, 129.05, 129.35, 132.24 (CH), 141.0, 146.36, 170.68 (C). For C21H20ClN3S calculated: 66.04% C, 5.28% H, 9.28% Cl, 11.00% N, 8.40% S; found: 65.88% C, 5.27% H, 9.26% Cl, 11.03% N, 8.41% S. HRMS (m/z): [M+H]+ calcd for C21H20ClN3S: 382.1139; found 382.1132.

2-[2-(4-Phenylcyclohexylidene)hydrazinyl]-4-(4-fluorophenyl)-thiazole (2m) Yield 68%. m.p. 182°C. IR (KBr, cm−1): ʋmax 3329 (N–H stretching), 3096–3008 (aromatic C–H), 2976–2858 (aliphatic C–H), 1610–1489 (C=N and C=C stretching). 1H-NMR (500 MHz, DMSO-d6, ppm) δ 1.60–1.68 (m, 2H, cyclohexyl-H), 1.97–2.09 (m, 3H, cyclohexyl-H), 2.39–2.47 (m, 2H, cyclohexyl-H), 2.85–2.88 (m, 1H, cyclohexyl-H), 3.17–3.20 (m 1H, cyclohexyl-H), 7.18–7.32 (m, 8H, Ar-H), 7.87–7.90 (m, 2H, Ar-H), 11.07 (s, 1H, NH). 13C-NMR (125 MHz, DMSO-d6, ppm) δ 27.42, 33.17, 34.44, 36.77 (CH2), 43.01 (CH), 103.53 (CH-thiazole), 115.81, 115.98 (2CH), 126.01 (CH), 126.58, 127.20 (2CH), 127.95, 128.01 (2CH), 128.84, 131.58 (2CH), 146.34, 155.43, 161.09, 163.03, 170.61 (C). For C21H20FN3S calculated: 69.01% C, 5.52% H, 5.20% F, 11.50% N, 8.77% S; found: 68.92% C, 5.50% H, 5.21% F, 11.52% N, 8.76% S. HRMS (m/z): [M+H]+ calcd for C21H20FN3S: 366.1435; found 366.1443.

2-[2-(4-Phenylcyclohexylidene)hydrazinyl]-4-(4-nitrophenyl)thiazole (2n) Yield 72%. m.p. 225°C. IR (KBr, cm−1): ʋmax 3311 (N–H stretching), 3113–3015 (aromatic C–H), 2947–2849 (aliphatic C–H), 1595–1469 (C=N and C=C stretching), 1504–1338 (NO2 stretching). 1H-NMR (500 MHz, DMSO-d6, ppm) δ 1.57–1.73 (m, 2H, cyclohexyl-H), 1.97–2.01 (m, 2H, cyclohexyl-H), 2.05–2.09 (m, 1H, cyclohexyl-H), 2.40–2.45 (m, 2H, cyclohexyl-H), 2.85–2.89 (m, 1H, cyclohexyl-H), 3.18–3.21 (m, 1H, cyclohexyl-H), 7.21–7.24 (m, 1H, Ar-H), 7.27–7.32 (m, 4H, Ar-H), 7.66 (s, 1H, thiazole-H), 8.12 (d, J=8.7 Hz, 2H, Ar-H), 8.28 (d, J=8.6 Hz, 2H, Ar-H), 11.08 (s, 1H, NH). 13C-NMR (125 MHz, DMSO-d6, ppm) δ 27.39, 33.16, 34.45, 35.03 (CH2), 43.02 (CH), 108,69 (CH-thiazole), 124.57 (2CH), 126.58 (CH), 127.20 (2CH), 128.83 (2CH), 141.44, 146.34, 146.57, 148.94, 155.17, 170.98 (C). For C21H20N4O2S calculated: 64.27% C, 5.14% H, 14.28% N, 8.15% O, 8.17% S; found: 64.38% C, 5.12% H, 14.30% N, 8.17% O, 8.14% S. HRMS (m/z): [M+H]+ calcd for C21H20N4O2S: 393.1380; found 393.1380.

2-[2-(4-Phenylcyclohexylidene)hydrazinyl]-4-(4-cyanophenyl)thiazole (2o) Yield 74%. m.p. 202°C. IR (KBr, cm−1): ʋmax 3307 (N–H stretching), 3111–3032 (aromatic C–H), 2978–2883 (aliphatic C–H), 1600–1435 (C=N and C=C stretching). 1H-NMR (500 MHz, DMSO-d6, ppm) δ 1.62–1.70 (m, 2H, cyclohexyl-H), 1.98–2.07 (m, 3H, cyclohexyl-H), 2.32-2.37 (m, 2H, cyclohexyl-H), 2.82–2.87 (m, 1H, cyclohexyl-H), 3.16–3.19 (m, 1H, cyclohexyl-H), 7.17–7.22 (m, 4H, Ar-H), 7.27–7.30 (m, 5H, Ar-H), 7.73 (d, J=8.1 Hz, 1H, Ar-H), 11.09 (s, 1H, NH). 13C-NMR (125 MHz, DMSO-d6, ppm) δ 21.26, 27.37, 33.18, 34.45 (CH2) 43.02 (CH), 102.83(CH-thiazole), 126.02 (CH), 125.97 (2CH), 126.57 (2CH), 127.20 (2CH), 128.83(2CH), 129.60, 137.22, 146.36, 170.43 (C). For C22H20N4S calculated: 70.94% C, 5.41% H, 15.04% N, 8.61% S; found: 71.12% C, 5.42% H, 15.00% N, 8.63% S. HRMS (m/z): [M+H]+ calcd for C22H20N4S: 373.1481; found 373.1477.

Antimicrobial activity assay

Antimicrobial activity studies were performed according to the following guides CLSI reference M07-A9 broth microdilution method [27] for bacterial strains and EUCAST definitive (EDef 7.1) method [28] for fungal strains. Tested microorganism strains were: Escherichia coli (ATCC 35218) (E. coli 1), Escherichia coli (ATCC 25922) (E. coli 2), Klebsiella pneumoniae (NCTC 9633), Pseudomonas aeuroginosa (ATCC 27853), Salmonella typhimurium (ATCC 13311) Staphylococcus aureus (ATCC 25923), Candida albicans (ATCC 24433), Candida glabrata (ATCC 90030), Candida krusei (ATCC 6258) and Candida parapsilosis (ATCC 22019). MIC90 readings were accomplished twice for all compounds. As reference drugs, chloramphenicol and ketoconazole were used.

Broth microdilution assay

Mueller-Hinton broth (Difco) was used to produce the bacterial strains. The strains were incubated at 37°C for 24h. The yeasts were produced in RPMI after night long incubation at 37°C. The inoculation of test microorganisms adjusted to match the turbidity of a Mac Farland 0.5 standard tube as determined with a spectrophotometer. For antibacterial and antifungal assays, the final inoculum size was 0.5–2.5×105 cfu/mL. For test, the two-fold serial dilutions technique utilized and test was carried out in Mueller–Hinton broth and RPMI at pH=7. As controls, the last well on the microplates including only inoculated broth was held. In order to present the MIC expressed in μg/mL, the last well with no growth of microorganism was registered. DMSO was used to dissolve compounds for both the antibacterial and antifungal assays. Further dilutions of the compounds and control drugs in test medium were equipped in the range of 1000, 500, 250, 125, 62.5, 31.25, 15.6, 7.8, 3.9 and 1.95 μg/mL concentrations with Mueller–Hinton broth, RPMI and Middle Brook medium. The finished plates were incubated for 24 h. At the end of this period, resazurin (20 μg/mL) was added into each well to control whether the growth in wells. After 2 h incubation of completed plates including each microorganism, MIC90 values were confirmed with a microplate reader at 590 nm excitation, 560 nm emission. Each experiment in the antimicrobial assays was performed twice. The MIC90 values are listed in Tables 1 and 2.

Results and discussion

Chemistry

In order to develop new effective anti-microbial agents, we synthesized a novel series of 4-(4-substitutedphenyl)-2-[2-[4-(ethyl/phenyl)cyclohexylidene] hydrazinyl]thiazole (2a–2o) and studied their antibacterial and antifungal activities. The final compounds were synthesized according to the steps as shown in Scheme 1. Firstly, 1-[4-(ethyl/phenyl)cyclohexylidene] thiosemicarbazide derivatives (compound 1a and 1b) were synthesized by the reaction of 4-(ethyl/phenyl)cyclohexanone with thiosemicarbazide. The reaction of equimolar quantities of compound 1a and 1b with appropriate phenacyl bromide in ethanol as solvent eventuated in the formation of the final compounds (2a–2o).

Scheme 1: Synthesis of the compounds. Reactans and reagents: (i) EtOH, acetic acid, reflux, 2 h, (ii) EtOH, 1–8 h, room temperature.
Scheme 1:

Synthesis of the compounds. Reactans and reagents: (i) EtOH, acetic acid, reflux, 2 h, (ii) EtOH, 1–8 h, room temperature.

Some characteristics of the synthesized compounds are shown in Table 3. Structures of the obtained compounds were confirmed by FT-IR, 1H-NMR, 13C-NMR, HRMS and elemental analysis.

In the IR spectra of the compounds (2a–2o), some significant specific bands were observed at 3381–3304 cm−1 and 1635–1435 cm−1 belong to N–H, C=N and C=C bonds.

In the 1H NMR spectra of all final compounds, the protons of cyclohexyl ring were observed at 1.01–3.18 ppm. A singlet peak due to thiazole ring was resonated at 7.07–8.62 ppm. The other protons in aromatic region were observed at the range of 6.91–8.34 ppm. The signals correspond to N–H residue were observed at about 10.71–11.09 ppm. The other aromatic and aliphatic protons were observed at the expected regions.

In the 13C NMR spectrum of the compounds, the signals belonging to –CH2–CH3 group in compounds 2a–2g, were determined at 11.85–12.14 ppm. The carbon atoms belonging to cyclohexyl ring were determined at 21.26–43.03 ppm. The signals belonging to C2 carbon of thiazole ring were resonated at 159.29–175.58 ppm all the other aromatic and aliphatic carbons were observed at expected regions.

Antimicrobial activity

MICs were recorded as the minimum concentration of a compound that inhibits the growth of tested microorganisms. The results are summarized in Tables 1 and 2. The antibacterial assessment showed that the compounds possess no useful inhibitory action. On the other hand, some of the compounds tested illustrated remarkable antifungal activity when compared with reference drug, ketoconazole. In the antifungal activity, compound 2h with nonsubstituted phenyl ring, compound 2l with para-chloro substituent on phenyl ring and compound 2m with para-fluoro substituent on phenyl ring exhibited significant antifungal activity against tested fungi species. According to results, it is clear that besides nonsubstituted derivative, halogen substituted derivatives possessed enhanced antimicrobial activity.

Table 1:

Antibacterial activity of the compounds (2a–o) as MIC values (mg/mL).

CompoundABCDEF
2a>1 mg/mL>1 mg/mL>1 mg/mL>1 mg/mL>1 mg/mL>1 mg/mL
2b>1 mg/mL>1 mg/mL>1 mg/mL>1 mg/mL>1 mg/mL>1 mg/mL
2c>1 mg/mL>1 mg/mL>1 mg/mL>1 mg/mL>1 mg/mL>1 mg/mL
2d>1 mg/mL>1 mg/mL>1 mg/mL>1 mg/mL>1 mg/mL>1 mg/mL
2e>1 mg/mL>1 mg/mL>1 mg/mL>1 mg/mL>1 mg/mL>1 mg/mL
2f>1 mg/mL>1 mg/mL>1 mg/mL>1 mg/mL>1 mg/mL>1 mg/mL
2g>1 mg/mL>1 mg/mL>1 mg/mL>1 mg/mL>1 mg/mL>1 mg/mL
2h>1 mg/mL>1 mg/mL>1 mg/mL>1 mg/mL>1 mg/mL>1 mg/mL
2i>1 mg/mL>1 mg/mL>1 mg/mL>1 mg/mL>1 mg/mL>1 mg/mL
2j>1 mg/mL>1 mg/mL>1 mg/mL>1 mg/mL>1 mg/mL>1 mg/mL
2k>1 mg/mL>1 mg/mL>1 mg/mL>1 mg/mL>1 mg/mL>1 mg/mL
2l>1 mg/mL>1 mg/mL>1 mg/mL>1 mg/mL>1 mg/mL>1 mg/mL
2m>1 mg/mL>1 mg/mL>1 mg/mL>1 mg/mL>1 mg/mL>1 mg/mL
2n>1 mg/mL>1 mg/mL>1 mg/mL>1 mg/mL>1 mg/mL>1 mg/mL
2o>1 mg/mL>1 mg/mL>1 mg/mL>1 mg/mL>1 mg/mL>1 mg/mL
Chloramphenicol≤1.95 μg/mL≤1.95 μg/mL3.9 μg/mL250 μg/mL≤1.95 μg/mL15.62 μg/mL

  1. A: Escherichia coli (ATCC 35218), B: Escherichia coli (ATCC 25922), C: Klebsiella pneumoniae (NCTC 9633), D: Pseudomonas aeuroginosa (ATCC 27853), E: Salmonella typhimurium (ATCC 13311), F: Staphylococcus aureus (ATCC 25923).

In comparing their MIC values with that of chloramphenicol, compound 2h and 2l, showed potency approximately four-fold better than a reference drug against C. albicans with MIC90 values of 1.95. In addition, compound 2h, 2l and 2m exhibited equal level of activity with ketoconazole against C. krusei and C. parapsilosis. Also compound 2h, 2l and 2m showed comparable activities against C. glabrata and the other compounds were found less active than the reference agent used.

Table 2:

Antifungal activity of the compounds (2a–o) as MIC values (mg/mL).

CompoundABCD
2a>1 mg/mL>1 mg/mL>1 mg/mL>1 mg/mL
2b>1 mg/mL>1 mg/mL>1 mg/mL>1 mg/mL
2c>1 mg/mL>1 mg/mL>1 mg/mL>1 mg/mL
2d>1 mg/mL>1 mg/mL>1 mg/mL>1 mg/mL
2e>1 mg/mL>1 mg/mL>1 mg/mL>1 mg/mL
2f>1 mg/mL>1 mg/mL>1 mg/mL>1 mg/mL
2g>1 mg/mL>1 mg/mL>1 mg/mL>1 mg/mL
2h≤1.95 μg/mL3.9 μg/mL≤1.95 μg/mL1.95 μg/mL
2i>1 mg/mL>1 mg/mL>1 mg/mL>1 mg/mL
2j>1 mg/mL>1 mg/mL>1 mg/mL>1 mg/mL
2k>1 mg/mL>1 mg/mL>1 mg/mL>1 mg/mL
2l≤1.95 μg/mL15.6 μg/mL≤1.95 μg/mL≤1.95 μg/mL
2m125 μg/mL125 μg/mL≤1.95 μg/mL1.95 μg/mL
2n>1 mg/mL>1 mg/mL>1 mg/mL>1 mg/mL
2o>1 mg/mL>1 mg/mL>1 mg/mL>1 mg/mL
Ketoconazole7.8 μg/mL≤1.95 μg/mL≤1.95 μg/mL≤1.95 μg/mL

  1. A: Candida albicans (ATCC 24433), B: Candida glabrata (ATCC 90030), C: Candida krusei (ATCC 6258), D: Candida parapsilosis (ATCC 22019).

Table 3:

Some properties of the compounds.

CompoundR1R2m.p. (°C)Yield (%)Molecular formula
2aEthylCH318765C18H23N3S
2bEthylOCH318464C18H23N3OS
2cEthylBr20468C17H20BrN3S
2dEthylCl18966C17H20ClN3S
2eEthylF18968C17H20FN3S
2fEthylNO218170C17H20N4O2S
2gEthylCN18969C18H20N4S
2hPhenylH19975C21H21N3S
2iPhenylCH320269C22H23N3S
2jPhenylOCH319272C22H23N3OS
2kPhenylBr20765C21H20BrN3S
2lPhenylCl17570C21H20ClN3S
2mPhenylF18268C21H20FN3S
2nPhenylNO222572C21H20N4O2S
2oPhenylCN20274C22H20N4S

Since, the addition of halogen substituents (in particular F, Cl, Br, I) will increase the lipophilicity of molecules and as consequence increase penetration to the bacterial cell [29], it appears that nonsubstitution or substitution on para position with chloro or fluoro on phenyl ring attached to the thiazole moiety contribute to the outstanding antifungal activity.

Conclusion

In the present study, we synthesized a new series of 4-(4-substitutedphenyl)-2-[2-[4-(ethyl/phenyl)cyclohexylidene] hydrazinyl]thiazole (2a–2o) derivatives and screen for their antibacterial and antifungal activity. According to the results, it was observed that some of the compounds exhibited remarkable effects. Among the them, compound 2h with nonsubstituted phenyl ring and compound 2l with chloro substituent at para position on phenyl ring were found to be the most promising antifungal agents with MIC values of 1.95 that is approximately four-fold better than the reference drug chloramphenicol against C. albicans.

  1. Conflict of interest: The authors declare no conflicts of interest.

References

1. Leeb M. Antibiotics: a shot in the arm. Nature 2004;431:892–3.10.1038/431892aSearch in Google Scholar

2. O’Connell KM, Hodgkinson JT, Sore HF, Welch M, Salmond GP, Spring DR. Combating multidrug-resistant bacteria: current strategies for the discovery of novel antibacterials. Angew Chem 2013;52:10706–33.10.1002/anie.201209979Search in Google Scholar

3. Silver LL. Challenges of antibacterial discovery. Clin Microbiol Rev 2011;24:71–109.10.1128/CMR.00030-10Search in Google Scholar

4. Taori K, Paul VJ, Luesch H. Structure and activity of largazole, a potent antiproliferative agent from the floridian marine cyanobacterium Symploca sp. J Am Chem Soc 2008;130:1806–7.10.1021/ja7110064Search in Google Scholar

5. Koti RS, Kolavi GD, Hegde VS, Khaji IM. Vilsmeier Haack reaction of substituted 2-acetamidothiazole derivatives and their antimicrobial activity. Ind J Chem 2006;45B:1900–4.10.1002/chin.200650142Search in Google Scholar

6. Guzeldemirci NU, Kucukbasmac O. Synthesis and antimicrobial activity evaluation of new 1,2,4-triazoles and 1,3,4-thiadiazoles bearing imidazo[2,1-b] thiazole moiety. Eur J Med Chem 2010;45:63–8.10.1016/j.ejmech.2009.09.024Search in Google Scholar

7. Bondock S, Khalifa W, Fadda AA. Synthesis and antimicrobial evaluation of some new thiazole, thiazolidinone and thiazoline derivatives starting from 1-chloro-3,4-dihydronaphthalene-2-carboxaldehyde. Eur J Med Chem 2007;42:948–54.10.1016/j.ejmech.2006.12.025Search in Google Scholar

8. Holla BS, Karegoudar P, Karthikeyan MS, Prasad DJ, Mahalinga M, Kumari NS. Synthesis of some novel 2,4-disubstituted thiazoles as possible antimicrobial agents. Eur J Med Chem 2008;43:261–7.10.1016/j.ejmech.2007.03.014Search in Google Scholar

9. Pandeya SN, Sriram D, Nath G, DeClerq E. Synthesis, antibacterial, antifungal and anti-HIV activities of Schiff and Mannich bases derived from isatin derivatives and N-[4-(40 - chlorophenyl) thiazol-2-yl] thiosemicarbazide. Eur J Pharm Sci 1999;9: 25–31.10.1016/S0928-0987(99)00038-XSearch in Google Scholar

10. Zitouni GT, Kaplancıklı ZA, Yıldız MT, Chevallet P, Kaya D. Synthesis and antimicrobial activity of 4-phenyl/cyclohexyl-5- (1-phenoxyethyl)-3-[N-(2-thiazolyl)acetamido]thio-4H–1,2,4-triazole derivatives. Eur J Med Chem 2005;40:607–13.10.1016/j.ejmech.2005.01.007Search in Google Scholar PubMed

11. Youssef AM, Malki A, Badr MH, Elbayaa RY, Sultan AS. Synthesis and anticancer activity of novel benzimidazole and benzothiazole derivatives against HepG2 liver cancer cells. Med Chem 2012;8:151–62.10.2174/157340612800493719Search in Google Scholar

12. Łączkowski KZ, Misiura K, Świtalska M, Wietrzyk J, Łączkowska AB, Fernández B, et al. Synthesis and in vitro antiproliferative activity of thiazole-based nitrogen mustards. The hydrogen bonding interaction between model systems and nucleobases. Anti-Cancer Agents Med Chem 2014;14:1271–81.10.2174/1871520614666140723115347Search in Google Scholar

13. Sharma RN, Xavier FP, Vasu KK, Chaturvedi SC, Pancholi SS. Synthesis of 4-benzyl-1,3-thiazole derivatives as potential anti-inflammatory agents: an analogue-based drug design approach. J Enzyme Inhib Med Chem 2009;24:890–7.10.1080/14756360802519558Search in Google Scholar

14. Nicolaou KC, Roschanger F, Vourloumis D. Chemical biology of epothilones. Angew Chem Int Ed 1998;37:2014–45.10.1002/(SICI)1521-3773(19980817)37:15<2014::AID-ANIE2014>3.0.CO;2-2Search in Google Scholar

15. Jeankumar VU, Kotagiri S, Janupally R, Suryadevara P, Sridevi JP, Medishetti R, et al. Exploring the gyrase ATPase domain for tailoring newer anti-tubercular drugs: hit to lead optimization of a novel class of thiazole inhibitors. Bioorg Med Chem Lett 2015;23:588–601.10.1016/j.bmc.2014.12.001Search in Google Scholar

16. Mathew V, Keshavayya J, Vaidya VP, Giles D. Studies on synthesis and pharmacological activities of 1, 2, 4-triazolo [3, 4-b] 1, 3, 4-thiadiazoles and their dihydro analogues. Arch Pharm Chem Life Sci 2009;342:210–22.10.1002/ardp.200800073Search in Google Scholar

17. Li Z, Khaliq M, Zhou Z, Post CB, Kuhn RJ, Cushman M. Design, synthesis, and biological evaluation of antiviral agents targeting flavivirus envelope proteins. J Med Chem 2008;51:4660–71.10.1021/jm800412dSearch in Google Scholar

18. Jaishree V, Ramdas N, Sachin J, Ramesh B. In vitro antioxidant properties of new thiazole derivatives. J Saudi Chem Soc 2012;16:371–6.10.1016/j.jscs.2011.02.007Search in Google Scholar

19. Bell FW, Cantrell AS, Hogberg M, Jaskunas SR, Johansson NG, Jordan CL, et al. Phenethylthiazolethiourea (PETT) compounds, a new class of HIV-1 reverse transcriptase inhibitors. 1. Synthesis and basic structure–activity relationship studies of PETT analogs. J Med Chem 1995;38:4929–36.10.1021/jm00025a010Search in Google Scholar

20. Patt WC, Hamilton HW, Taylor MD, Ryan MJ, Taylor DG Jr, Connolly CJ, et al. Structure–activity relationships of a series of 2-amino-4-thiazole containing renin inhibitors. J Med Chem 1992;35:2562–72.10.1021/jm00092a006Search in Google Scholar

21. Jaen JC, Wise LD, Caprathe BW, Tecle H, Bergmeier S, Humblet CC, et al. 4-(1,2,5,6- Tetrahydro-1-alkyl-3-pyridinyl)-2-thiazolamines: a novel class of compounds with central dopamine agonist properties. J Med Chem 1990;33:311–17.10.1021/jm00163a051Search in Google Scholar

22. Hargrave KD, Hess FK, Oliver JT. N-(4-Substitutedthiazolyl) oxamic acid derivatives, new series of potent, orally active antiallergy agents. J Med Chem 1983;26:1158–63.10.1021/jm00362a014Search in Google Scholar

23. Carter JS, Kramer S, Talley JJ, Penning T, Collins P, Graneto MJ, et al. Synthesis and activity of sulfonamide-substituted 4,5-diaryl thiazoles as selective cyclooxygenase-2 inhibitors. Bioorg Med Chem Lett 1999;9:1171–4.10.1016/S0960-894X(99)00157-2Search in Google Scholar

24. Richard JH, Robertson A, Ward J. Experiments on the synthesis of rotenone and its derivatives. Part XV. J Chem Soc 1948:1610–2.10.1039/jr9480001610Search in Google Scholar PubMed

25. Turan-Zitouni G, Chevallet P, Erol K, Boydağ BS. Synthesis of some chroman derivatives and preliminary investigation on their vasodilatory activity. Farmaco 1997;52:569–71.Search in Google Scholar

26. Pirbasti FG, Mahmoodi NO. Facile synthesis and biological assays of novel 2,4-disubstituted hydrazinyl-thiazoles analogs. Mol Divers 2016;20:497–506.10.1007/s11030-015-9654-7Search in Google Scholar PubMed

27. Clinical and Laboratory Standards Institute. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard—Ninth Edition. CLSI document M07-A9.Search in Google Scholar

28. EUCAST Definitive Document EDef 7.1: method for the determination of broth dilution MICs of antifungal agents for fermentative yeasts.Search in Google Scholar

29. Pliška V, Testa B, van de Waterbeemd H. Lipophilicity in drug action and toxicology. Methods and principles in medicinal chemistry. Hoboken: John Wiley and Sons, 2008.Search in Google Scholar

Received: 2017-03-29
Accepted: 2017-06-12
Published Online: 2017-11-28
Published in Print: 2018-05-01

©2018 Walter de Gruyter GmbH, Berlin/Boston

Articles in the same Issue

  1. Frontmatter
  2. Research Articles
  3. Comparative study of stirred and fluidized tank reactor for hydroxyl-kojic acid derivatives synthesis and their biological activities
  4. Synthesis and antimicrobial activities of some novel thiazole compounds
  5. Water based PHEMA hydrogels for controlled drug delivery
  6. Cultural conditions optimization for production of β-galactosidase from Bacillus licheniformis ATCC 12759 under solid-state fermentation
  7. A novel application of oriental beetle juvenile Anomala corpulenta to reflect Pb contamination in soil
  8. Purification and characterization of Rhizoctonia solani AG-4 strain ZB-34 α-amylase produced by solid-state fermentation using corn bran
  9. Grain amino acid composition of barley (Hordeum vulgare L.) cultivars subjected to selenium doses
  10. Microsatellite-based characterization of cotton genotypes for verticillium wilt and fiber quality traits
  11. Novel pectinase from Piriformospora indica, optimization of growth parameters and enzyme production in submerged culture condition
  12. Application of Bdellovibrio bacteriovorus for reducing fouling of membranes used for wastewater treatment
  13. Large unstained cells are correlated with inflammatory biomarkers in patients with invasive aspergillosis
  14. Detection of industrially potential enzymes of moderately halophilic bacteria on salted goat skins
  15. Strain improvement of newly isolated Lactobacillus acidophilus MS1 for enhanced bacteriocin production
  16. The effects of hydraulic calcium silicate containing endodontic materials on oxidative stress in erythrocytes and liver
https://doi.org/10.1515/tjb-2017-0093
Keywords for this article
Antibacterial activity; Antifungal activity; Thiazole; Broth microdilution method

Articles in the same Issue

  1. Frontmatter
  2. Research Articles
  3. Comparative study of stirred and fluidized tank reactor for hydroxyl-kojic acid derivatives synthesis and their biological activities
  4. Synthesis and antimicrobial activities of some novel thiazole compounds
  5. Water based PHEMA hydrogels for controlled drug delivery
  6. Cultural conditions optimization for production of β-galactosidase from Bacillus licheniformis ATCC 12759 under solid-state fermentation
  7. A novel application of oriental beetle juvenile Anomala corpulenta to reflect Pb contamination in soil
  8. Purification and characterization of Rhizoctonia solani AG-4 strain ZB-34 α-amylase produced by solid-state fermentation using corn bran
  9. Grain amino acid composition of barley (Hordeum vulgare L.) cultivars subjected to selenium doses
  10. Microsatellite-based characterization of cotton genotypes for verticillium wilt and fiber quality traits
  11. Novel pectinase from Piriformospora indica, optimization of growth parameters and enzyme production in submerged culture condition
  12. Application of Bdellovibrio bacteriovorus for reducing fouling of membranes used for wastewater treatment
  13. Large unstained cells are correlated with inflammatory biomarkers in patients with invasive aspergillosis
  14. Detection of industrially potential enzymes of moderately halophilic bacteria on salted goat skins
  15. Strain improvement of newly isolated Lactobacillus acidophilus MS1 for enhanced bacteriocin production
  16. The effects of hydraulic calcium silicate containing endodontic materials on oxidative stress in erythrocytes and liver
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