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SYNTHESIS AND ANTIMICROBIAL ACTIVITY EVALUATION OF NEW
DITHIOCARBAMATE DERIVATIVES BEARING
THIAZOLE/BENZOTHIAZOLE RINGS
Leyla Yurttaş1*, Yusuf Özkay1, Murat Duran2, Gülhan Turan-Zitouni1, Ahmet Özdemir1,
Zerrin Cantürk3, Kaan Küçükoğlu4, Zafer Asım Kaplancıklı1
1Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Anadolu University, 26470,
Eskisehir, Turkey
2Faculty of Arts & Sciences, Department of Chemistry, Eskisehir Osmangazi University, 26480,
Eskisehir, Turkey
3Faculty of Pharmacy, Department of Microbiology, Anadolu University, 26470, Eskisehir,
Turkey
4Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Ataturk University, 25240,
Erzurum, Turkey
Email: [email protected]
Supplemental Materials
Biological Activity
Antimicrobial activity evaluation
Several title compounds exhibited high activity against to the identified microorganisms
compared with standard drugs. Among 2-[(benzo)thiazol-2-ylamino]-2-oxoethyl 4-(pyrimidin-2-
yl)piperazin-1-carbodithioate derivatives (B1-B14), B2, 10-14 (200 µg/mL) exhibited same
activity against E. faecalis (ATCC 51922) when B12 showed half activity potential (100 µg/mL)
against L. monocytogenes (ATCC 1911). Compounds B11-13 exhibited same activity (200
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µg/mL) with chloramphenicol against Pseudomonas aeruginosa (ATCC 27853). Among E. coli
species compound B12 bearing 4-ethoxycarbonylthiazole moiety exhibited two-fold high
antibacterial activity compared with standard drug when the other E. coli (ATCC 25922) strain
failed to show any noticeable activity. Compounds B1, 3, 10-12 and 14 showed remarkable
anticandidal activity against C. albicans (ATCC 90028) and C. glabrata (ATCC 90030). In
this series, both antibacterial and antifungal activity evaluation, compound B12 bearing 4-
ethoxycarbonylthiazole moiety was determined as the most active compound and thiazole
including compounds were detected to show higher activity than benzothiazole including
compounds. Compounds 2-(substituted phenyl) 4-(pyrimidin-2-yl)piperazin-1-carbodithioate
(A1-A24) were detected to exhibit lower antimicrobial activity than B1-B14 compounds and the
antifungal activity of the compounds A1-A24 was greater than antibacterial activity of them.
Compound A18 bearing 3-fluorophenyl and A21 bearing 3,4-difluorophenyl moiety showed
same antibacterial potential with chloramphenicol against Pseudomonas aeruginosa (ATCC
27853) and E. coli (ATCC 35218). Against these series (A1-A24), C. albicans was found as the
most susceptible microorganism. When compared ketoconazole, A21 showed two-fold
antifungal activity potential and the other compounds in the series exhibited same potency with
standard drug.
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Table S 1. Antimicrobial activity of the compounds 2-(substituted phenyl)-2-oxoethyl 4-
(pyrimidin-2-yl)piperazin-1-carbodithioate derivatives (A1-A24) (µg/mL)
I II III IV V VI VII VIII IX X XI XIIA1 400 800 800 800 400 400 400 400 200 200 200 200A2 400 200 800 400 400 400 400 400 200 200 200 200A3 800 800 800 800 800 800 800 800 200 200 200 200A4 800 800 800 800 800 800 800 800 200 200 200 200A5 400 800 800 800 400 400 400 400 200 200 100 100A6 400 800 800 800 400 400 400 400 400 200 200 200A7 400 800 800 800 400 400 400 400 200 200 100 100A8 400 800 800 800 400 400 400 400 400 200 200 200A9 400 800 800 800 400 400 400 400 200 200 200 200A10 800 800 800 800 800 800 800 800 200 200 200 200A11 800 800 800 800 800 800 800 800 200 200 200 200A12 400 800 800 400 400 400 400 400 200 200 200 200A13 400 800 800 800 800 800 800 800 400 200 200 400A14 400 400 800 400 400 400 400 400 200 200 200 200A15 800 800 800 800 800 800 800 800 200 200 200 200A16 400 400 800 400 400 400 400 400 200 200 200 200A17 400 800 800 800 400 200 400 400 200 200 200 200A18 400 800 800 800 400 200 200 400 200 200 100 100A19 400 800 800 800 800 800 800 800 400 200 200 400A20 800 800 800 800 800 800 800 200 200 200 200 200A21 400 800 800 800 400 200 200 400 200 100 50 50A22 400 800 800 800 400 400 400 400 200 200 200 200A23 400 800 800 800 400 400 400 400 200 200 200 200A24 400 400 800 800 400 400 400 400 200 200 200 400Ref 50 3.13 200 50 100 200 200 50 200 200 50 25
I: Staphylococcus aureus (ATCC 25923); II: Enterococcus faecalis (ATCC 29212); III: Enterococcus
faecalis (ATCC 51922; IV: Listeria monocytogenes (ATCC 1911); V: Klebsiella pneumoniae (ATCC
700603); VI: Pseudomonas aeruginosa (ATCC 27853); VII: Escherichia coli (ATCC 35218); VIII:
Escherichia coli (ATCC 25922); IX: Candida albicans (ATCC 90028); X: Candida glabrata (ATCC
90030); XI: Candida krusei (ATCC 6258); XII: Candida parapsilopsis (ATCC 22019)
Reference drugs: Chloramphenicol; ketoconazole
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Table S2. Antimicrobial activity of the compounds 2-[(benzo)/thiazol-2-ylamino)-2-oxoethyl 2-
oxoethyl 4-(pyrimidin-2-yl)piperazin-1-carbodithioate derivatives (B1-B14) (µg/mL)
I II III IV V VI VII VIII IX X XI XII
B1 400 400 400 400 400 400 400 200 200 200 200 200
B2 400 400 200 400 800 400 200 200 200 200 200 200
B3 400 400 400 400 400 400 200 200 200 200 200 200
B4 400 800 400 800 800 400 200 200 800 800 800 800
B5 400 800 800 800 800 400 200 200 800 800 400 800
B6 400 200 200 200 200 400 200 200 200 200 200 200
B7 400 800 800 800 800 400 200 200 800 800 800 800
B8 400 800 800 800 800 800 200 200 800 800 800 800
B9 400 800 800 800 800 800 200 200 800 800 800 800
B10 400 200 200 200 200 400 200 200 200 200 200 200
B11 400 400 200 400 800 200 400 200 200 200 200 200
B12 400 400 200 100 200 200 100 200 100 200 100 100
B13 400 800 200 800 800 200 200 200 800 800 800 800
B14 400 800 200 800 800 800 200 200 200 200 800 200
Ref 50 3.13 200 50 100 200 200 50 200 200 50 25
I: Staphylococcus aureus (ATCC 25923); II: Enterococcus faecalis (ATCC 29212); III: Enterococcus
faecalis (ATCC 51922; IV: Listeria monocytogenes (ATCC 1911); V: Klebsiella pneumoniae (ATCC
700603); VI: Pseudomonas aeruginosa (ATCC 27853); VII: Escherichia coli (ATCC 35218); VIII:
Escherichia coli (ATCC 25922); IX: Candida albicans (ATCC 90028); X: Candida glabrata (ATCC
90030); XI: Candida krusei (ATCC 6258); XII: Candida parapsilopsis (ATCC 22019)
Reference drugs: Chloramphenicol; ketoconazole
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Figure S 1: 1H-NMR spectrum of compound A2
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Figure S 2: 13C-NMR spectrum of compound A2
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Figure S 3: 1H-NMR spectrum of compound A3
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Figure S 4: 1H-NMR spectrum of compound A4
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Figure S 5: 1H-NMR spectrum of compound
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Figure S 6: 13C-NMR spectrum of compound A8
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Figure S 7: 1H-NMR spectrum of compound A10
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Figure S 8: 13C-NMR spectrum of compound A10
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Figure S 11: 13C-NMR spectrum of compound A13
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Figure S 12: 1H-NMR spectrum of compound A14
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Figure S 13: 1H-NMR spectrum of compound A15
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Figure S 14: 1H-NMR spectrum of compound A19
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Figure S 15: 1H-NMR spectrum of compound A20
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Figure S 16: 1H-NMR spectrum of compound A23
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Figure S 17: 13C-NMR spectrum of compound A23
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Figure S 18: 1H-NMR spectrum of compound A24
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Figure S 19: 1H-NMR spectrum of compound B1
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Figure S 20: 13C-NMR spectrum of compound B1
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Figure S 21: 1H-NMR spectrum of compound B2
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Figure S 22: 13C-NMR spectrum of compound B2
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Figure S 23: 1H-NMR spectrum of compound B3
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Figure S 24: 13C-NMR spectrum of compound B3
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Figure S 25: 1H-NMR spectrum of compound B4
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Figure S 26: 13C-NMR spectrum of compound B4
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Figure S 27: 1H-NMR spectrum of compound B5
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Figure S 28: 13C-NMR spectrum of compound B5
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Figure S 29: 1H-NMR spectrum of compound B6
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Figure S 30: 1H-NMR spectrum of compound B7
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Figure S 31: 13C-NMR spectrum of compound B7
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Figure S 32: 1H-NMR spectrum of compound B8
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Figure S 33: 13C-NMR spectrum of compound B8
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Figure S 34: 1H-NMR spectrum of compound B9
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Figure S 35: 1H-NMR spectrum of compound B10
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Figure S 36: 13C-NMR spectrum of compound B10
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Figure S 37: 1H-NMR spectrum of compound B11
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Figure S 38: 1H-NMR spectrum of compound B12
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Figure S 39: 13C-NMR spectrum of compound B12
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Figure S 40: 1H-NMR spectrum of compound B13
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Figure S 41: 13C-NMR spectrum of compound B13
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Figure S 42: 1H-NMR spectrum of compound B14
