L.-Y. Li, B.-L. Fei, P. Wang et al.
Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 246 (2021) 118944
Scheme 1. Synthesis route of the target compounds 8 and 9.
BSA binding abilities and primary cytotoxic activities were studied here.
We tried to explore the relationship between the cytotoxic activities
and DNA/BSA binding affinities of such compounds.
1311. 1H NMR (600 MHz, CDCl3), δ (ppm): 8.704 (1H, d, J = 4.8 Hz),
8.277(1H, d, J = 7.8 Hz), 7.935–7.964 (1H, m), 7.561–7.583 (1H, m),
7.203 (1H, d, J = 7.8 Hz), 7.011–7.027 (1H, m), 6.864 (1H, d, J =
1.2 Hz), 2.805–2.855 (3H, m), 2.415 (1H, d, J = 12.6 Hz), 2.168 (1H,
dd, J = 12.6, 1.8 Hz), 1.816–1.967 (6H, m), 1.655 (3H, s), 1.548–1.622
(1H, m), 1.473–1.506 (1H, m), 1.329 (3H, s), 1.224 (6H, d, J = 6.6 Hz).
13C NMR (101 MHz, CDCl3), δ (ppm): 177.69, 161.90, 158.06, 148.80,
147.42, 146.67, 145.91, 137.90, 134.69, 127.71, 127.01, 124.18, 124.06,
123.17, 77.48, 77.16, 76.84, 50.89, 44.31, 42.73, 38.29, 38.00, 33.56,
30.13, 25.71, 24.11, 24.05, 20.61, 19.33, 19.24.
2. Materials and methods
2.1. Materials and instruments
All the chemicals and solvents were obtained from commercial
sources and used as received, except DHA and dichloromethane
(DCM) were purified according to the standard procedures.
1H/13C NMR, IR, circular dichroism (CD), UV–vis, fluorescence, vis-
cosity and C, H and N analysis were carried out on Bruker Avance III
HD 600 MHz spectrometer (Switzerland), Nicolet 380 FT-IR spectrome-
ter, Jasco J-810 spectropolarimeter, TU-1901 UV–vis spectrophotometer
(Beijing Purkinje General Instrument Co., Ltd), Perkin-Elmer LS-55 fluo-
rescence spectrophotometer, Ubbelodhe viscometer and Elementar
Vario Micro elemental analyzer, respectively.
2.2.2. Synthesis of di-N-(5-dehydroabietyl-1,3,4-thiadiazole)-yl-pyridine-
2,6-carboxamide (9)
Triethylamine (4 mL) and 2 (2.04 g, 20 mmol) were dissolved in
40 mL dry dichloromethane, respectively, and then added dropwise to
the solution of 3 (3.55 g, 10 mmol) in 60 mL dry DCM, separately,
under the condition of ice bath and vigorously stirring. The reaction
progress was monitored by TLC. 24 h later, the reaction solution was
washed alternately with 5% HCl (3 × 45 mL) and saturated NaHCO3
(3 × 45 mL). The resulted organic phase was collected, combined with
the DCM extraction of the aqueous phase, and dried with MgSO4 over-
night. The crude product was obtained after getting rid of DCM, white
powder could be afforded after recrystallization from the mixed solvent
of methanol and DCM (v/v = 3:1) in 63% yield. Single crystal suitable for
X-ray diffraction was obtained by diffusion of acetone into tetrahydro-
furan solution of 9. m.p. 244–245 °C. CD (nm): 195 (positive), 200 (neg-
ative), 205 (positive), 213 (negative), 221 (negative), 230 (positive).
Anal. cald. for C49H59N7O2S2 (%): C, 69.88; H, 7.06; N, 11.64; found: C,
69.90; H, 7.04; N, 11.65. MS (m/z): 842.18 [M]+. IR (ν, cm−1, KBr pellet):
3320, 3145, 2859, 2827, 2777, 1585, 1438, 1363. 1H NMR (600 MHz,
CDCl3), δ (ppm): 8.480 (2H, d, J = 7.8 Hz), 8.123–8.149 (1H, m),
7.187 (2H, d, J = 8.4 Hz), 7.006–7.023 (2H, m), 6.842 (2H, d, J =
1.2 Hz), 3.751–3.773 (2H, m), 2.694–2.848 (6H, m), 2.385 (2H, d, J =
13.2 Hz), 2.097 (2H, dd, J = 12, 1.8 Hz), 1.747–1.872 (12H, m), 1.553
(6H, s), 1.384–1.419 (2H, m), 1.292 (6H, s), 1.225 (12H, d, J = 7.2 Hz).
13C NMR (101 MHz, CDCl3), δ (ppm): 177.38, 161.37, 158.90, 147.26,
146.54, 145.82, 139.53, 134.52, 126.92, 126.74, 124.07, 123.97, 68.00,
50.49, 44.10, 42.54, 38.12, 37.82, 33.48, 30.98, 29.97, 25.65, 25.55,
24.03, 23.98, 20.50, 19.17, 19.12.
2.2. Synthesis
The synthetic procedure is shown in Scheme 1. 2, 3 and N-(5-
dehydroabietyl-1,3,4-thiadiazole)-yl-pyridine-2-carboxamide
(8)
were prepared according to literature [1]. The synthesis of 5 and 7
were based on the literature method [13,14].
2.2.1. Synthesis of N-(5-dehydroabietyl-1,3,4-thiadiazole)-yl-pyridine-2-
carboxamide (8)
Triethylamine (2 mL) and 2 (1.42 g, 10 mmol) were dissolved in
20 mL dry dichloromethane, respectively, and then added dropwise to
the solution of 3 (3.55 g, 10 mmol) in 30 mL dry dichloromethane, sep-
arately, under the condition of ice bath and vigorously stirring. The reac-
tion process was monitored by thin layer chromatography (TLC), 4 h
later, 30 mL water was added to the above mixture and quenched the
reaction. Then, the organic phase was separated and the aqueous
phase was extracted with dichloromethane (3 × 20 mL). The combined
organic phase was dried with MgSO4 overnight. After filtration and re-
duced evaporation, the obtained crude product was purified by column
chromatography on silica, eluted with petroleum ether-ethyl acetate
(3:1) to give 8 as white powders in 63% yield. Single crystal suitable
for X-ray diffraction was obtained by slow evaporation the solution of
8 in methanol and water (v/v = 9:1). m.p. 135–137 °C. CD (nm): 195
(positive), 200 (negative), 205 (positive), 213 (negative), 221 (nega-
tive), 230 (positive). Anal. cald. for C27H32N4OS (%): C, 70.40; H, 7.00;
2.3. DNA and BSA binding studies
N, 12.16; found: C, 70.42; H, 6.98; N, 12.15. MS (m/z): 461.2 [M+1]+
IR (ν, cm−1, KBr pellet): 3346, 3259, 3247, 2854, 2763, 1604, 1432,
.
The corresponding techniques are referred to the methods used in
the published papers of our group [1].
2