Synthesis, characterization, and antimicrobial activities of novel monosaccharide-containing Schiff base ligands

Article abstract of DOI:10.3906/kim-1606-76

Four new chiral Schiff base ligands (3a–4a, 3b–4b) have been prepared using aminoisopropylidene derivatives of glucose and aminochloralose derivatives of mannose. The synthesized compounds 1 and 2 were characterized by nuclear magnetic resonance (¹

Full text of DOI:10.3906/kim-1606-76

Turk J Chem
Turkish Journal of Chemistry
(2017) 41: 370 – 380
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http://journals.tubitak.gov.tr/chem/
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c
⃝ TUBITAK
doi:10.3906/kim-1606-76
Research Article
Synthesis, characterization, and antimicrobial activities of novel
monosaccharide-containing Schiff base ligands
∗
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Fatma C¸ ETIN TELLI, Stephen Thomas ASTLEY, Azize Ye¸sim SALMAN
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Department of Chemistry, Faculty of Science, Ege University, Izmir, Turkey
Received: 24.06.2016
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Accepted/Published Online: 17.11.2016
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Final Version: 16.06.2017
Abstract: Four new chiral Schiff base ligands (3a–4a, 3b–4b) have been prepared using aminoisopropylidene derivatives
of glucose and aminochloralose derivatives of mannose. The synthesized compounds 1 and 2 were characterized by nuclear
magnetic resonance (1 H and 13 C NMR), Fourier transform infrared spectroscopy (FTIR), UV/visible spectroscopy, and
elemental analysis. A total of eight Schiff base compounds (3a–6a, 3b–6b) were tested for antimicrobial activity against
Escherichia coli ATCC 12228, Staphylococcus aureus ATCC 6538, Klebsiella pneumoniae CCM 2318, Pseudomonas
aeruginosa ATCC 27853, Salmonella typhimurium CCM 5445, Enterococcus faecalis ATCC 29212, Bacillus subtilis
ATCC 6633, and Candida albicans ATCC 10239 and exhibited a range of activities.
Key words: Chloralose, ONO-tridentate chiral Schiff base, amino sugar, antimicrobial activity
1. Introduction
Schiff bases, named after Hugo Schiff,1 are formed when a primary amine reacts with an aldehyde or a ketone.
Structurally, a Schiff base is a nitrogen analogue of a carbonyl compound in which the carbonyl group has been
replaced by an imine or azomethine group (Figure 1).
Figure 1. Mechanism of the synthesis of Schiff base (imine) from amine and aldehyde or ketone.
Schiff base ligands are easily synthesized and form complexes with almost all metal ions. Over the
past few years, there have been many reports on their biological properties including antibacterial, antifungal,
anticancer, antioxidant, antiinflammatory, antimalarial, antiviral, and antimicrobial activities.2−7 In addition,
they can act as catalysts in several reactions such as polymerization, reduction of thionyl chloride, oxidation
of organic compounds, reduction reaction of ketones, aldol reaction, Henry reaction,8,9 epoxidation of alkenes,
hydrosilylation of ketones, and Diels–Alder reaction.
Monosaccharides mostly react in their furanose forms with chloral to give trichloroethylidene acetals.
Chloraloses (β -chloralose or α-glucochloralose) have been prepared by the simple reaction of chloral and
∗Correspondence: yesim.salman@ege.edu.tr
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glucose.10 Thus, 1,2-O-trichloroethylideneacetals of D-glucofuranose,11 D-galactofuranose,12 D-arabinofurano-
se,13 and D-mannofuranose14 are known. 1,2-O-(R)-trichloroethylidene-D-glucofuranose is a commercially
available compound, also known as α-chloralose, which is used as an anesthetic for animals.15 Unlike other
acetals, 1,2-O-trichloroethylidene acetals are highly stable in the presence of acids. This is attributed to the
electron-withdrawing ability of the trichloromethyl group. By contrast, they offer much less stability under even
mildly basic conditions and they can be converted to synthetically useful ketene acetals in the presence of strong
bases. Alternatively, the 1,2-O-trichloroethylidene acetal can be removed using a Raney nickel procedure.11
They have proved to be suitable protecting groups for the synthesis of some biologically important compounds
such as amines,16 lactones,17 orthoesters,13,14 spiroendoperoxides,18 spirodifuranose,19 O-glycosides,20 uranic
acid,21 oxime,22 oxetanes,23 Wittig products,24 and Schiff base ligands.25
As part of ongoing studies into the chemistry of monosaccharide trichloroethylidene acetals, we recently
synthesized some ONO-tridentate chiral Schiff bases. Based on previous observations,9 it was expected that
a bulky sugar moiety could be expected to have a significant effect on the catalytic activity of these ligands.
Thus, when these ONO-tridentate Schiff base ligands were employed as chiral ligands for the Cu(II) catalyzed
asymmetric Henry reaction, high yields and good enantioselectivities were obtained.25
It has recently been pointed out that a sugar moiety plays a major role in the biological activity
of carbohydrate-based Schiff bases.26 Considering that it is well known that tridentate Schiff base ligands
themselves exhibit interesting biological activity27−29 we decided that it could be beneficial to investigate the
biological activity of a series of Schiff base ligands containing different sugar substituents. Herein we describe
the preparation of aminoisopropylidene glucose Schiff bases (3a, 3b) and aminochloralose Schiff base derivatives
of mannose (4a, 4b) (Figure 1). Their biological activities are compared with those of Schiff base ligands from
aminochloralose-containing glucose (5a, 5b) and galactose (6a, 6b) derivatives (Figure 2).25
Figure 2. Structure of Schiff base ligands (3a–6a, 3b–6b) from aminoisopropylidene derivatives of glucose (3) and
aminochloralose derivatives of mannose (4), glucose (5), and galactose (6).
2. Results and discussion
Our methods of formation of the ONO-tridentate chiral Schiff base ligands involved initial preparation of
aminosugars via selective tosylation of the corresponding furanose. As shown in the Scheme, this was followed
by azidation, reduction, and subsequent reaction with aldehyde (3,5-di-t-butylsalicylaldehyde or salicylaldehyde)
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to give the targeted ONO-tridentate chiral Schiff bases. The yields of these reactions were very high (70% to
87%). All products were characterized by elemental analysis and by 1 H NMR,13 C NMR, UV, and FTIR
spectroscopic methods.
Scheme. Synthesis of aminosugar derivatives (3–4) and Schiff base derivatives (3a–4a, 3b–4b).
In the UV/visible spectra, run in ethanol, three distinct bands were observed at 280 nm, 338 nm, and
375 nm. The absorption at 280 nm can be assigned to a π → π∗ transition involving the aromatic rings and
the absorption at 338 nm can be assigned to the π → π∗ transition for the C = N chromophore.30,31 The
final band around 375 nm corresponds to the n → π * transitions of the nonbonding electrons present in the
nitrogen of the azomethine group of the Schiff base.32
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The infrared (IR) spectra of the ligands exhibit a broad absorption band at 3463 cm−1 that corresponds
to the hydroxyl protons of the Schiff base ligands. The broadness and the low frequency values indicate the
presence of significant intramolecular hydrogen bonding of the phenolic O−H group33,34 and the hydroxyl
groups in positions 6 and 3 of the ONO chiral Schiff base ligands. A strong absorption band dominates the
spectrum between 1630 and 1640 cm−1 . This band is attributed to the C=N vibration characteristic of imines.
As expected, there is no evidence of the characteristic band related to free aromatic aldehydes group near 1665
cm−1
.
1 H and 13 C NMR data of the Schiff base derivatives are given in Tables 1 and 2. The characteristic
chemical shift of the azomethine (CH=N) protons is observed at 8.40 ppm as a singlet. In addition, the
aromatic protons appear as multiplets of δ values in the range 6.84–7.90 ppm.35,36 One sharp singlet appeared
at δ 5.76 ppm in the spectrum assigned to the acetal proton of D-mannochloralose. The methyl protons of the
isopropylidine group and tert-butyl groups were observed between δ 1.28 and 1.47 ppm as singlets.
Table 1. 1 H NMR (400 MHz) chemical shifts (δ ppm) in CDCl3 , for Schiff base derivatives (3a–4a, 3b–4b).
Compd CH=N Aromatic protons
H-1 H-2 H-3 H-4 H-5 H-6a H-6b H-CCl3 CH3
3a
3b
4a
4b
8.37
8.39
8.40
8.42
7.33, 7.25, 6.93, 6.84 5.96 4.55 4.40 4.11 4.32 4.00 3.73
7.38, 7.21 6.06 4.60 4.32 4.06 4.21 3.99 3.75
7.64, 7.55, 6.95, 6.87 6.09 4.92 4.51 4.30 4.27 3.87 3.68 5.77
7.90, 7.41 6.12 4.98 4.48 4.31 4.18 3.97 3.76 5.76
-
-
1.47, 1.30
1.45, 1.28
-
1.44, 1.32
As seen in Table 3, the Schiff base ligands showed antimicrobial activity against gram positive/negative
bacteria and C. albicans at different concentrations. Schiff bases are known to have a variety of biological prop-
erties including antibacterial, antifungal, antimalarial, antiproliferative, and antiviral activities.37 Surprisingly,
however, none of the compounds exhibited activity against S. aureus ATCC 6538 except compound 4b. In con-
trast, all of the compounds except 4b and 6a exhibited activity against S. thyphimirium CCM 5445. The Schiff
base ligand from aminochloralose mannose (4a) exhibited activity against only S. thyphimirium CCM 5445
and B. subtilis ATCC 6633, whereas the other Schiff base ligand from aminochloralose mannose (4b) exhibited
activity against only E. coli ATCC 12228 and S. aureus ATCC 6538. In addition, Schiff base ligands (3b and
6a) in the concentration range 0.1–0.2 mg/mL proved to be effective against E. faecalis ATCC 29212. Having
been a hospital pathogen and secondary infection agent, this antimicrobial activity against P. aeruginosa is a
property of only Schiff base ligands from aminochloralose glucose (5a and 5b). Thus, it may be concluded that
Schiff base ligands from aminochloralose glucose (5a and 5b) possess similar antimicrobial activity, which is
uncommon among other Schiff base ligands. Comparing the overall activities of all eight Schiff bases, it appears
that the glucose derivatives 3a, 3b, 5a, and 5b seem to have slightly greater activity than the mannose and
galactose derivatives. This could suggest that the particular chiral configuration of glucose has an important
role. To the best of our knowledge, this appears to be the first study of the antibacterial activities of Schiff
base ligands from aminochloralose derivatives of glucose, mannose, and galactose and also aminoisopropylidene
derivatives of glucose. The positive results reported here suggest that further work into the preparation and
properties of this type of compound may prove beneficial.
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3. Experimental
3.1. Materials
All 1 H NMR and 13 C NMR spectra were recorded using a Varian AS 400+ Mercury FT NMR spectrometer at
ambient temperature. IR spectra were recorded on a PerkinElmer 100 FTIR spectrometer. UV/vis spectra were
obtained using a Shimadzu UV-1601 spectrophotometer. Optical rotations were determined using a Rudolph
Research Analytical Autopol I automatic polarimeter with a wavelength of 589 nm. The concentration ‘c’ has
units of g/100 mL. Elemental analyses were performed on a PerkinElmer PE 2400 elemental analyzer. TLC
and column chromatography were performed on precoated aluminum plates (Merck 5554) and silica gel G-60
(Merck 7734), respectively. All solvent removals were carried out under reduced pressure.
3.2. General procedure for the preparation of aminosugar derivatives (3 and 4)
The preparation of amino monosaccharides has been well reported in the recent literature.25 Recent stud-
ies by Yenil and Astley have described the preparation of a series of aminosugar chloralose derivatives.16,25
In the present study the main objective was to develop a simple method for the preparation of the 6-
amino derivatives of 1,2,5,6-O-diisopropylidene-α-D-glucofuranose (diacetone-D-glucose) (1) and 1,2-O-(R)-
trichloroethylidene-β -D-mannofuranose (2). Initial work included the synthesis of the starting compound,
specifically the trichloroethylidene acetal of D-mannose, according to literature procedures.13 Then the target
molecules (3 and 4) were synthesized in a three-step sequence. First of all, the hydroxyl group in position 6 of
the monosaccharide derivatives (0.10 mol) (1 or 2) was tosylated using p-toluenesulfonyl chloride (0.11 mol) in
pyridine at –5 ◦ C for 12 h. The reaction mixture was concentrated to half volume and then poured into ice-water
(250 mL) to remove the pyridine. Then it was extracted with 150 mL of dichloromethane three times and then
the organic phase was treated with 100 mL of water (three times). Subsequently, the dichloromethane phase
was dried by adding anhydrous sodium sulfate (Na2 SO4) and then filtered. The dichloromethane was evapo-
rated and then the residue, containing the monotosyl furanose derivative, was obtained in the pure state using
column chromatography. The eluting solvents were a dichloromethane and methanol mixture (CH2 Cl2 :MeOH,
50:2). In the second reaction, we performed nucleophilic substitution of the tosyl group with an azide group.
To a solution of the 6-O-tosyl derivative of the monosaccharide (0.10 mol) in dimethylforamide (DMF) (50 mL)
was added sodium azide (0.125 mol). The reaction mixture was then stirred in an oil bath at 150 ◦ C for 3 h. At
this point, TLC (CH2 Cl2 :MeOH, 8:2) indicated that the reaction was complete and so the reaction mixture was
decanted into ice-water (250 mL). Afterwards, the water phase was extracted with 100 mL of dichloromethane
(three times) and the dichloromethane phase was collected and washed with 100 mL of water three times. Drying
of the dichloromethane phase was carried out by adding anhydrous sodium sulfate (Na2 SO4) and then filtering.
The dichloromethane was evaporated under reduced pressure and the 6-azide derivative of monosaccharide was
obtained. The final step was to reduce the azide group to an amine functionality using triphenyl phosphine
(PPh3).25 The aminoisopropylidene derivatives of glucose (3) and aminochloralose derivatives of mannose (4)
were prepared in high yields of 70% and 75%.
3.2.1. Synthesis of 6-amino-6-deoxy-1,2-O-isopropylidene-α-D-glucofuranose (3)
The aminoisopropylidene derivative of D-glucose (3) was prepared in 70% yield. [α]2D3 = –6.2, (c 0.65, EtOH);
IR cm−1 (KBr); 3356 (–NH2 and –OH), 1578 (N–H). 1 H NMR (δ ppm, DMSO-d6): 5.75 (d, 1H, J = 4.0 Hz,
H-1), 4.35 (d, 1H, J = 4.0 Hz, H-2), 4.10 (br s, 4 H, –NH2 , –OH), 4.01 (s, 1H, H-3), 3.99 (d, 1H, J = 8.0 Hz ,
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H-4), 3.74 (dd, 1H,J = 12.6, 8.0 Hz, H-6a), 3.65 (m, 1H, H-5), 2.74 (dd, 1H, J = 12.6, 8.0 Hz, H-6b), 1.34 and
1.19 (2s, CH3 -isopropylidene); 13 C NMR: 110.8, 104.8 (Cisopropylidene , C-1), 85.1, 82.3, 73.5 (C-2, C-3, C-4),
68.2 (C-5), 46.0 (C-6), 27.1, 26.5 (Me group).
Anal. Calc. for C9 H17 NO5 : C, 49.31; H, 7.82; N, 6.39. Found: C, 49.25; H, 7.65; N, 6.49.
3.2.2. Synthesis of 6-amino-6-deoxy-1,2-O-(R)-trichloroethylidene- β -D-mannofuranose (4)
The aminochloralose derivative of D-mannose (4) was prepared in 75% yield. [α]2D3 = + 11.7, (c 0.60, EtOH).
IR cm−1 (KBr); 3366 (–NH2 and –OH), 1594 (N–H). 1 H NMR (δ ppm, DMSO-d6 ,): 6.17 (d, J = 3.6 Hz, 1
H, H-1), 5.72 (s, 1 H, HC-CCl3), 5.00 (d, J = 3.6 Hz, 1 H, H-2), 4.66 (s, 1 H, H-3), 4.28 (m, 1 H, H-4), 3.62
(m, 1 H, H-5), 3.15, 2.78 (dd, J = 16.0, 4.0 Hz, 2 H, H-6), 2.30 (br s, 4 H, –NH2 , –OH); 13 C NMR: 109.3,
108.5 (HC -CCl3 , C -1), 99.6 (HC-C Cl3), 90.8, 90.3, 83.2 (C -2, C -3, C -4), 71.7 (C -5), 49.0 (C -6).
Anal. Calc. for C8 H12 Cl3 NO5 : C, 31.14; H, 3.92; N, 4.54. Found: C, 31.45; H, 3.95; N, 4.49.
3.3. General procedure for the synthesis of the ONO-tridentate chiral Schiff bases (3a–4a, 3b–4b)
Ethanol (5 mL) solution of aldehyde (salicylaldehyde or 3,5-ditbutylsalicylaldehyde) (10 mmol) was added
dropwise into an ethanol (5 mL) solution of the appropriate amino sugar derivative (10 mmol). After stirring
for 3 h at room temperature, the solvent was evaporated and the remaining residue was crystallized from
diethylether and light petroleum ether to afford yellow crystals in yields of 70%–87%.
3.3.1. Synthesis of 6-deoxy-1,2-O-(S)-isopropylidene-6-[(2’-ylimino)methyl] phenol-α-D-glucofu-
ranose (3a)
The title product was prepared in 76% yield. mp = 79–81 ◦ C, [α]D22 = –12.7 (c 0.5, CH2 Cl2); IR (KBr), 3390,
2936, 1634, 1582, 1497, 1462, 1280, 1160, 1060, 828, 805, 757 cm−1 . UV/vis (EtOH) λmax (nm): 280, 338,
375. 1 H NMR (CDCl3 , δ ppm) 8.37 (s, 1H, –CH=N–), 7.33 (m, 1H, Ar-H), 7.25 (dd, J = 12.0 Hz, 4.0 Hz,
1H, Ar-H), 6.93 (d, J = 8 Hz, 1H, Ar-H), 6.84 (m, 1H, Ar-H), 5.96 (d, 1H, J = 4.0 Hz, H-1), 4.55 (d, 1H, J
= 4.0 Hz, H-2), 4.40 (d, J = 3.0 Hz, 1H, H-3), 4.32 (m, 1H, H-5), 4.11 (dd, J = 9.0 Hz, 3.0 Hz, H-4), 4.00
(dd, 1H, H-6a), 3.73 (dd, 1H, J = 12.0 Hz, 8.0 Hz, H-6b), 1.47 and 1.30 (2s, CH3 – isopropylidene); 13 C NMR:
168.4, 164.7, 135.4, 133.2, 119.9, 118.7, 116.9, 109.9, 105.3, 85.9, 82.5, 74.1, 68.7, 48.6, 27.1, 23.2.
Anal. Calcd for C16 H21 NO6 : C, 59.43; H, 6.55; N, 4.33. Found: C, 59.64; H, 6.70; N, 4.21.
3.3.2. Synthesis of 6-deoxy-1,2-O-(S)-isopropylidene-6-[2’,4’-ter-butyl-(6’-ylimino) methyl]phenol-
α-D-glucofuranose (3b)
The title product was prepared in 70% yield. mp = 59–61 ◦ C, [α]D22 = +10.8 (c 0.50, CH2 Cl2); IR (KBr),
3412, 2958, 1634, 1470, 1442, 1273, 1162, 1011, 828, 855, 749 cm−1 . UV/vis (EtOH) λmax (nm): 282, 335,
376. 1 H NMR (CDCl3 , δ ppm) 8.39 (s, 1H, –CH=N–), 7.38 (d, J = 4 Hz, 1H, Ar-H), 7.21 (m, 1H, Ar-H),
6.06 (d, 1H, J = 3.6 Hz, H-1), 4.60 (d, 1H, J = 3.6 Hz, H-2), 4.32 (d, 1H, J = 4.0, H-3), 4.21 (m, 1H, H-5),
4.06 (d, 1H, H-3), 3.99 (dd, 1H, J = 12.0 Hz, 8.0 Hz, H-6a), 3.75 (d, 1H, H-6b), 1.45 and 1.28 (s, 24H, CH3);
13 C NMR: 167.3, 159.1, 137.6, 132.9, 130.7, 118.3, 117.8, 107.5, 105.2, 87.4, 82.4, 76.1, 69.4, 62.5, 38.3, 36.7,
35.1, 34.3, 31.7, 31.0, 29.4, 29.2, 23.1, 20.9.
Anal. Calcd for C24 H37 NO6 : C, 66.18; H, 8.56; N, 3.22. Found: C, 66.27; H, 8.69; N, 3.28.
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3.3.3. 6-Deoxy-1,2-O-(S)-trichloroethylidene-6-[(2’-ylimino)methyl]phenol-β -D-mannofuranose
(4a)
The title product was prepared in 87% yield. mp = 97–99 ◦ C, [α]D22 = +17.4 (c 0.40, CH2 Cl2); IR (KBr),
3410, 2955, 1631, 1470, 1438, 1368, 1276, 1156, 1032, 829, 811, 751 cm−1 . UV/vis (EtOH) λmax (nm): 288,
340, 370. 1 H NMR (CDCl3 , δ ppm) 8.40 (s, 1H, –CH=N–), 7.64 (m, 1H, Ar-H), 7.55 (dd, J = 8.0 Hz, 6.2
Hz, 1H, Ar-H), 6.95 (d, J = 8.0 Hz, 1H, Ar-H), 6.87 (m, 1H, Ar-H), 6.09 (d, 1H, J = 3.6 Hz, H-1), 5.77 (s,
1H, HCCl3), 4.92 (d, J = 3.6 Hz, 1H, H-2), 4.51 (d, 1H, J = 4.0 Hz , H-3), 4.30 (d, J = 2.8 Hz, H-4), 4.27
(m, 1H, H-5), 3.87 (dd, , J = 12.6, 8.0 Hz, 1H, H-6b), 3.68 (d, 1H, J = 12.6, 8.0 Hz, H-6a); 13 C NMR: 167.5,
161.6, 132.6, 132.1, 119.1, 118.6, 117.0, 109.4, 105.1, 99.5, 83.2, 82.8, 69.6, 67.7, 62.2.
Anal. Calcd for C15 H16 Cl3 NO6 : C, 43.66; H, 3.91; N, 3.39. Found: C, 43.87; H, 3.83; N, 3.45.
3.3.4. 6-Deoxy-1,2-O-(S)-trichloroethylidene-6-[2’,4’-ter-butyl-(6’-ylimino)methyl] phenol-β -D-
mannofuranose (4b)
The title product was prepared in 80% yield. mp = 65–67 ◦ C, [α]D22 = +10.8 (c 0.50, CH2 Cl2); IR (KBr),
3377, 2961, 1640, 1467, 1439, 1273, 1169, 1026, 828, 801, 750 cm−1 . UV/vis (EtOH) λmax (nm): 284, 335,
380. 1 H NMR (CDCl3 , δ ppm) 8.44 (s, 1H, –CH=N–), 7.90 (d, J = 2.0 Hz, 1H, Ar-H), 7.41 (m, 1H, Ar-H)
6.12 (d, 1H, J = 3.6 Hz, H-1), 5.76 (s, 1H, HCCl3), 4.98 (d, 1H,J = 3.6 Hz, H-2), 4.48 (d,1H, J = 4.0, H-3),
4.31 (m, 1H, H-4), 4.18 (dd, 1H, J = 12.0, 8.0 Hz, H-5), 3.97 (dd, 1H, J = 12.0, 8.0 Hz, H-6a), 3.76 (d, J
= 12.0 Hz, 1H, H-6b) 1.44 and 1.32 (s, 18H, CH3); 13 C NMR: 167.3, 159.1, 141.6, 137.6, 131.9, 130.0, 128.3,
107.3, 105.4, 97.6, 87.4, 88.4, 76.7, 69.3, 62.3, 37.8, 36.9, 35.0, 34.2, 31.6, 31.2, 29.4, 29.2.
Anal. Calcd for C23 H32 Cl3 NO6 : C, 52.63; H, 6.15; N, 2.67. Found: C, 52.78; H, 6.31; N, 2.75.
3.4. Antimicrobial activities of the compounds (3a–6a and 3b–6b)
The in vitro antimicrobial activity of the synthesized compounds (3a–6a and 3b–6b) was studied against the
following bacterial strains of gram-positive organisms: Staphylococcus aureus ATCC6538-P, Bacillus subtilis
ATCC 6633, and Enterococcus faecalis ATCC 29212, and gram-negative organisms: Escherichia coli ATCC
12228, Pseudomonas aeruginosa ATCC 27853, Salmonella typhimurium CCM 5445, and Klebsiella pneumoniae
CCM 2318 and unicellular yeast Candida albicans ATCC 10239, by microdilution method. Briefly, all com-
pounds were dissolved in 10% dimethylsulfoxide (DMSO). Then serial dilutions of each sample were performed
in 10% DMSO. Inocula for assays were prepared from activated cultures in Mueller-Hinton broth (MHB) by
dilution to give a final viable cell count of 4.0–5.5 × 105 CFU/mL. Each sample solution (25 µL) and inoculum
of test microorganism (25 µL) were added into each well of a flat-bottom, 96-well microtiter plate prefilled with
200 µL of MHB to give a total volume of 250 µL. Microtiter plates were incubated at 37 ◦ C for 24 h for bacteria
and 48–72 h for C. albicans. The solvent, 10% DMSO, was used as the negative control for all experiments.
After incubation, the MIC value was detected by adding 50 µL of 0.5% triphenyltetrazolium chloride (TTC)
aqueous solution.38,39 MIC was defined as the lowest concentration of extract that inhibited visible growth as
indicated by the TTC reduction. In the presence of bacterial growth by reduction reactions, TTC changes the
color of microbial cells from colorless to red. This provides clearly defined and easily readable endpoints. All
tests were repeated three times to confirm the results.
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4. Conclusions
Our studies results are in line with the literature although there are very limited studies on antimicrobial
activities of similar compounds. For example, it was reported that the Schiff base derivatives of D-glucose
amine showed biological activity when evaluated for antimicrobial activity against gram-positive and gram-
negative bacterial and fungi strains.36 In our studies, four new chiral Schiff base ligands (3a–4a, 3b–4b) were
prepared from aminoisopropylidene derivatives of glucose (3) and aminochloralose derivatives of mannose (4).
The chiral Schiff base ligands containing the aminofuranose moiety from glucose, mannose, and galactose showed
a range of antimicrobial activities.
Acknowledgment
We wish to thank Prof Dr Ihsan Ya¸sa for carrying out the antimicrobial studies and his helpful discussions.
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