DOI: 10.1080/14756366.2016.1209495
Bioactivity studies of 1-aryl-3-(2-hydroxyethylthio)-1-propanones
3
Table 2. Spectral data of the compounds EU1–EU9.
EU1
EU2
EU3
EU4
1H NMR (400 MHz, CDCl3, ppm) d ¼ 7.87–7.85 (m, 2H), 7.49–7.46 (m, 1H), 7.38–7.34 (m, 2H), 3.72–3.68 (m, 2H), 3.50 (brs, OH, 1H),
39.2, 35.5, 26.2. HRMS (ESI–MS): calcd. for C11H14O2S [M + H]+ 211.0748; found 211.0793.
3.21–3.16 (m, 2H), 2.88–2.82 (m, 2H), 2.70–2.66 (m, 2H). 13C NMR (100 MHz, CDCl3, ppm) d ¼ 198.8, 136.6, 133.6, 128.9, 128.2, 61.2,
1H NMR (400 MHz, CDCl3, ppm) d ¼ 7.79 (d, J ¼ 8.4 Hz, 2H), 7.19 (d, J ¼ 8.4 Hz, 2H), 3.73 (m, 2H), 3.20 (t, J ¼ 6.9 Hz, 2H), 3.16 (s, OH,
1H), 2.88 (t, J ¼ 6.9 Hz, 2H), 2.71 (t, J ¼ 6.9 Hz, 2H), 2.34 (s, 3H). 13C NMR (100 MHz, CDCl3, ppm) d ¼ 198.3, 144.4, 134.2, 129.6,
128.4, 61.1, 39.0, 35.6, 26.3, 21.9. HRMS (ESI–MS): calcd. for C12H16O2S [M + H]+ 225.0905; found 225.0949.
1H NMR (400 MHz, CDCl3, ppm) d ¼7.77 (d, J ¼ 8.8 Hz, 2H), 6.78 (d, J ¼ 8.8 Hz, 2H), 3.70 (s, 3H), 3.65 (t, J ¼ 6.7 Hz, 2H), 3.56 (s, OH,
1H), 3.08 (t, J ¼ 6.7 Hz, 2H), 2.78 (t, J ¼ 6.7 Hz, 2H), 2.63 (t, J ¼ 6.7 Hz, 2H). 13C NMR (100 MHz, CDCl3, ppm) d ¼ 197.3, 163.8, 130.5,
129.6, 114.0, 61.2, 55.6, 38.7, 35.4, 26.4. HRMS (ESI–MS): calcd. for C12H16O3S [M + H]+ 241.0854; found 241.0898.
1H NMR (400 MHz, CDCl3, ppm) d ¼7.91 (dd, J ¼ 8.0, 5.7 Hz, 2H), 7.06 (t, J ¼ 8.0 Hz, 2H), 3.72 (q, J ¼ 6.5 Hz, 2H), 3.20 (t, J ¼ 6.5 Hz,
2H), 3.13 (bs, OH, 1H), 2.87 (t, J ¼ 6.5 Hz, 2H), 2.70 (t, J ¼ 6.5 Hz, 2H). 13C NMR (100 MHz, CDCl3, ppm) d ¼ 197.1, 166.0
(1J ¼ 255 Hz), 133.1 (4J ¼ 3 Hz), 130.9 (3J ¼ 9 Hz), 116.0 (2J ¼ 21 Hz), 61.0, 39.0, 35.6, 26.1. HRMS (ESI–MS): calcd. for C11H13FO2S
[M + H]+ 229.0654; found 229.0699.
EU5
EU6
EU7
EU8
EU9
1H NMR (400 MHz, CDCl3, ppm) d ¼ 7.83 (d, J ¼ 8.8 Hz, 2H), 7.37 (d, J ¼ 8.8 Hz, 2H), 3.73 (t, J ¼ 6.5 Hz, 2H), 3.21 (t, J ¼ 6.5 Hz, 2H),
2.98 (s, OH, 1H), 2.88 (t, J ¼ 6.5 Hz, 2H), 2.72 (t, J ¼ 6.5 Hz, 2H). 13C NMR (100 MHz, CDCl3, ppm) d ¼ 197.4, 140.0, 135.0, 129.7,
129.2, 61.0, 39.1, 35.7, 26.1. HRMS (ESI–MS): calcd. for C11H13ClO2S [M + H]+ 245.0325; found 245.0403.
1H NMR (400 MHz, CDCl3, ppm) d ¼ 7.82 (d, J ¼ 8.6 Hz, 2H), 7.62 (d, J ¼ 8.6 Hz, 2H), 3.78 (q, J ¼ 6.4 Hz, 2H), 3.26 (t, J ¼ 6.4 Hz, 2H),
2.95 (t, J ¼ 6.4 Hz, 2H), 2.78 (t, J ¼ 6.4 Hz, 2H). 13C NMR (100 MHz, CDCl3, ppm) d ¼ 197.4, 132.3, 131.7, 129.8, 126.6, 60.7, 39.1,
36.0, 25.9. HRMS (ESI-MS): calcd. for C11H13BrO2S [M + H]+ 288.9820; found 288.9898.
1H NMR (400 MHz, CDCl3, ppm) d ¼ 7.68 (dd, J ¼ 3.6, 1.1 Hz, 1H), 7.60 (dd, J ¼ 4.8, 1.1 Hz, 1H), 7.08 (dd, J ¼ 4.8, 3.6 Hz, 1H), 3.71 (m,
2H), 3.18–3.15 (m, 2H), 2.89–2.85 (m, 2H), 2.72–2.68 (m, 2H). 13C NMR (100 MHz, CDCl3, ppm) d ¼ 191.6, 143.9, 134.4, 132.6, 128.5,
61.1, 39.7, 35.6, 26.3. HRMS (ESI–MS): calcd. for C9H12O2S2 [M + H]+ 217.0312; found 217.0356.
1H NMR (400 MHz, CDCl3, ppm) d ¼ 7.57 (br s, 1H), 7.20 (d, J ¼ 3.7 Hz, 1H), 6.52 (dd, J ¼ 3.7, 1.8 Hz, 1H), 3.74 (t, J ¼ 6.0 Hz, 2H), 3.13–
3.08 (m, 2H), 2.90–2.84 (m, 2H), 2.74–2.70 (m, 2H). 13C NMR (100 MHz, CDCl3, ppm) d ¼ 187.7, 152.6, 147.0, 117.8, 112.7, 60.9, 38.8,
35.6, 25.9. HRMS (ESI–MS): calcd. for C9H12O3S [M + H]+ 201.0541; found 201.0580.
1H NMR (400 MHz, CDCl3, ppm) d ¼ 8.32 (d, J ¼ 9.0 Hz, 2H), 8.11 (d, J ¼ 9.0 Hz, 2H), 3.79 (t, J ¼ 6.3 Hz, 2H), 3.34 (t, J ¼ 6.3 Hz, 2H),
2.97 (t, J ¼ 6.3 Hz, 2H), 2.79 (t, J ¼ 6.3 Hz, 2H). 13C NMR (100 MHz, CDCl3, ppm) d ¼ 197.0, 141.1, 129.8, 129.3, 124.2, 60.9, 39.8,
35.9, 25.8. HRMS (ESI–MS): calcd. for C11H13NO4S [M + H]+ 256.0599; found 256.0644.
Table 3. Cytotoxic activities of the compounds EU1–EU9.
CC50 (mM)
Human OSCC cell lines
Human oral normal cells
HPC
HSC-2
HSC-3
HSC-4
HL-60
HGF
HPLF
TS
EU1
EU2
EU3
EU4
EU5
EU6
EU7
EU8
4400
4400
4400
4400
4400
4400
4400
4400
4400
4400
4400
4400
4400
340 58
338 38
4400
167 17
158 15
4400
4400
15 1
10 1.1
4400
4400
4400
4400
4400
4400
4400
4400
4400
4400
4400
4400
39 2.0
4100
4400
331 32
4400
451.0
451.0
451.0
451.0
41.2
4400
337
4
292
8
380
6
328
5
317 12
321 21
4400
336 16
4400
377 16
302 40
320 20
363 30
50 8
47 7.2
19 0.58
4400
4400
4400
322 13
4400
325 41
41.2
451.1
450.97
1.3
46.2
5.5
4400
EU9
5-FU
Melphalan
49
6
68
2
72
2
64 16
4100
80 0.58
4.9 0.91
6.2 0.32
2.5 0.25
36 1.7
4100
96 6.4
1.0 0.04
83 4.5
CC50 values refer to the concentrations of the compounds in micromoles which reduce the viable cell number by 50%. Tumor-specific (TS) value is
calculated by dividing the mean CC50 value of each compound against normal cells to mean CC50 value against OSCC. CC50 value was determined
from the growth curves plotted at different concentrations of each compounds in triplicate wells. Human oral squamous cell carcinoma cell lines
(HSC-2, HSC-3, HSC-4), human promyelocytic leukemic cell line (HL-60), human oral normal mesenchymal cells (gingival fibroblast (HGF), pulp
cells (HPC), periodontal ligament fibroblast (HPLF). TS: tumour selectivity; mM: micromolar.
Carbonic anhydrase inhibition assay
deionized water and dilutions up to 0.01 nM were done thereafter
with the assay buffer. Inhibitor and enzyme solutions were
preincubated together for 15 min at room temperature prior to
assay, in order to allow for the formation of the E-I complex. The
inhibition constants were obtained by nonlinear least-squares
squares methods, values representing the mean of at least three
different determinations, as described earlier by us31. All enzymes
used were recombinant, produced in E. coli and the cell pellets
were lysed and enzyme was purified through affinity chromatog-
An Applied Photophysics stopped-flow instrument has been used
for assaying the CA-catalyzed CO2 hydration activity by using the
method of Khalifah30. Phenol red (at a concentration of 0.2 mM)
has been used as indicator, working at the absorbance maximum
of 557 nm, with 20 mM Hepes (pH 7.5) as buffer, and 20 mM
Na2SO4 (for maintaining constant the ionic strength), following
the initial rates of the CA-catalyzed CO2 hydration reaction for a
period of 10–100 s. The CO2 concentrations ranged from 1.7 to
17 mM for the determination of the kinetic parameters and
inhibition constants. For each inhibitor, at least six traces of the
initial 5–10% of the reaction have been used for determining
the initial velocity. The uncatalyzed rates were determined in the
raphy using pAMBS resin as reported earlier24,32–34
.
Results and discussion
same manner and subtracted from the total observed rates. Stock In this study, the designed compounds, 1-aryl-3-(2-hydro-
solutions of inhibitor (0.1 mM) were prepared in distilled and xyethylthio)-1-propanones, were successfully synthesized by the