11. (a) Salas, P. F.; Herrmann, C.; Cawthray, J. F.; Nimphius, C.;
Kenkel, A.; Chen, J.; de Kock, C.; Smith, P. J.; Patrick, B. O.;
Adam, M. J.; Orvig, C. J. Med. Chem. 2013, 56, 1596; (b)
Sharma, P.; Chhabra, S.; Rai, N.; Ghoshal, N. J. Chem. Inf.
Model. 2007, 47, 1087; (c) Boström, J.; Grant, J. A.; Fjellström,
O.; Thelin, A.; Gustafsson, D. J. Med. Chem. 2013, 56, 3273; (d)
Hirayama, T.; Okaniwa, M.; Banno, H.; Kakei, H.; Ohashi, A.;
Iwai, K.; Ohori, M.; Mori, K.; Gotou, M.; Kawamoto, T.; Yokota,
A.; Ishikawa, T. J. Med. Chem. 2015, 58, 8036.
12. (a) Ramakrishnan, P.; Maclean, M.; MacGregor, S. J.; Anderson,
J. G.; Grant, M. H. Toxicology in Vitro 2016, 33, 54; (b) Hu, L.;
Li, L.; Xu, D.; Xia, X.; Pi, R.; Xu, D.; Wang, W.; Du, H.; Song,
E.; Song, Y. Chem. Biol. Interact. 2014, 213, 51; (c) Kumar, S.;
Rhim, W. K.; Lim, D. K.; Nam, J. M. ACS Nano 2013, 7, 2221.
13. (a) Cui, S. F.; Ren, Y.; Zhang, S. L.; Peng, X. M.; Damu, G. L. V.;
Geng, R. X.; Zhou, C. H. Bioorg. Med. Chem. Lett. 2013, 23,
3267; (b) Zhang, H. Z.; Jeyakkumar, P.; Kumar, K. V.; Zhou, C.
H. New J. Chem. 2015, 39, 5776; (c) Peng, L. P.; Nagarajan, S.;
Rasheed, S.; Zhou, C. H. Med. Chem. Comm. 2015, 6, 222.
are currently in progress, and all these will be discussed in the
future paper.
Acknowledgments
This work was partially supported by National Natural
Science Foundation of China [(No. 21372186), the Research
Fund for International Young Scientists from International
(Regional) Cooperation and Exchange Program NSFC (No.
81450110451)], the Specialized Research Fund for the Doctoral
Program of Higher Education of China (SRFDP
20110182110007) and Chongqing Special Foundation for
Postdoctoral Research Proposal (Xm2015031).
References and notes
14. (a) Yin, B. T.; Yan, C. Y; Peng, X. M.; Zhang, S. L.; Rasheed, S.;
Geng, R. X.; Zhou, C. H. Eur. J. Med. Chem. 2014, 71, 148; (b)
Ni, Y.; Dua, S.; Kokot, S. Anal. Chim. Acta 2007, 584, 19; (c)
Gong, H. H.; Baathulaa, K.; Lv, J. S.; Cai, G. X.; Zhou, C. H.
MedChemCommun 2016, DOI: 10.1039/C5MD00574D.
1.
2.
(a) Weir, K. Nature 2015, 528, S130; (b) McKenney, P. T.; Pamer,
E. G. Cell 2015, 163, 1326; (c) Escoll, P.; Mondino, S.; Rolando,
M.; Buchrieser, C. Nat. Rev. Microbiol. 2016, 14, 5; (d) Peng, X.
M.; Cai, G. X.; Zhou, C. H. Curr. Top. Med. Chem. 2013, 13,
1963; (e) Zhou, C. H.; Wang, Y. Curr. Med. Chem. 2012, 19, 239.
(a) Ni, W. J.; Ding, H. H.; Tang, L. Q. Eur. J. Pharmacol. 2015,
760, 103; (b) Bansal, Y.; Silakari, O. Eur. J. Med. Chem. 2014, 76,
31; (c) Kumar, A.; Ekavali, C. K.; Mukherjee, M.; Pottabathini,
R.; Dhull, D. K. Eur. J. Pharmacol. 2015, 761, 288; (d) Kaboli, P.
J.; Rahmat, A.; Ismail, P.; Ling, K. H. Eur. J. Pharmacol. 2014,
740, 584.
15. Experimental: Melting points are determined on X–6 melting
point apparatus and uncorrected. IR spectra were determined on a
Bio-Rad FTS-185 spectrophotometer in the range of 400–4000
1
cm-1. H NMR and 13C NMR spectra were recorded on a Bruker
AV 600 or Varian 300 spectrometer using TMS as an internal
standard. Chemical shifts were reported in parts per million
(ppm), the coupling constants (J) were expressed in hertz (Hz)
and signals were described as singlet (s), doublet (d), triplet (t), as
well as multiplet (m). The mass spectra (MS) were recorded on
LCMS–2010A and the high-resolution mass spectra (HRMS)
were recorded on an IonSpec FT-ICR mass spectrometer with ESI
resource. All chemicals and solvents were commercially
available, and used without further purification. The UV spectrum
3.
4.
Tillhon, M.; Ortiz, L. M. G.; Lombardi, P.; Scovassi, A. I.
Biochem. Pharmacol. 2012, 84, 1260.
(a) Domadia, P. N.; Bhunia, A.; Sivaraman, J.; Swarup, S.;
Dasgupta, D. Biochemistry 2008, 47, 3225; (b) Ball, A. R.;
Casadei, G.; Samosorn, S.; Bremner, J. B.; Ausubel, F. M.; Moy,
T. I.; Lewis, K. ACS Chem. Biol. 2006, 1, 594; (c) Xu, Y.; Wang,
Y.; Yan, L.; Liang, R. M.; Dai, B. D.; Tang, R. J.; Gao, P. H.;
Jiang, Y. Y. J. Proteome Res. 2009, 8, 5296; (d) Domadia, P. N.;
Bhunia A.; Sivaraman, J.; Swarup, S.; Dasgupta, D. Biochemistry
2008, 47, 3225.
(a) Zhang, L.; Chang, J. J.; Zhang, S. L.; Damu, G. L. V.; Geng,
R. X.; Zhou, C. H. Bioorg. Med. Chem. 2013, 21, 4158; (b)
Zhang, S. L.; Chang, J. J.; Damu, G. L. V.; Fang, B.; Zhou, X. D.;
Geng, R. X.; Zhou, C. H. Bioorg. Med. Chem. Lett. 2013, 23,
1008; (c) Zhang, S. L.; Chang, J. J.; Damu, G. L. V.; Geng, R. X.;
Zhou, C. H. Med. Chem. Comm. 2013, 4, 839.
was recorded at room temperature on
a
TU-2450
spectrophotometer (Puxi Analytic Instrument Ltd. of Beijing,
China) equipped with 1.0 cm quartz cells. The concentration of
DNA in stock solution was determined by UV absorption at 260
nm using a molar absorption coefficient ξ260 = 6600 L mol-1 cm-1
(expressed as molarity of phosphate groups) by Bouguer–
Lambert–Beer law. The purity of the DNA was checked by
monitoring the ratio of the absorbance at 260 nm to that at 280
nm. The solution gave a ratio of > 1.8 at A260/A280, which
indicates that DNA was sufficiently free from protein. All of the
solutions were adjusted with Tris-HCl buffer solution (pH = 7.4),
which was prepared by mixing and diluting Tris solution with
HCl solution. All chemicals were of analytical reagent grade, and
doubly distilled water was used throughout.
5.
6.
7.
(a) Li, R.; Wu, J.; He, Y.; Hai, L.; Wu, Y. Bioorg. Med. Chem.
Lett. 2014, 24, 1762; (b) Iwasa, K.; Lee, D. U.; Kang, S. I.;
Wiegrebe, W. J. Nat. Prod. 1998, 61, 1150.
(a) Zhang, L.; Peng, X. M.; Damu, G. L. V.; Geng, R. X.; Zhou,
C. H. Med. Res. Rev. 2014, 34, 340; (b) Zhang, L.; Kumar, K. V.;
Rasheed, S.; Zhang, S. L.; Geng, R. X.; Zhou, C. H.
MedChemCommun 2015, 6, 1405; (c) Peng, X. M.; Damu, G. L.
V.; Zhou, C. H. Curr. Pharm. Des. 2013, 19, 3884; (d) Zhang, L.;
Addla, D.; Ponmani, J.; Wang, A.; Xie, D.; Wang, Y. N.; Zhang,
S. L.; Geng, R. X.; Cai, G. X.; Li, S.; Zhou, C. H. Eur. J. Med.
Chem. 2016, 111, 160; (e) Zhang, L.; Kumar, V. K.; Geng, R. X.;
Zhou, C. H. Bioorg. Med. Chem. Lett. 2015, 25, 3699; (f) Damu,
G. L. V.; Cui, S. F.; Peng, X. M.; Wen, Q. M.; Cai, G. X.; Zhou,
C. H. Bioorg. Med. Chem. Lett. 2014, 24, 3605.
Berberine hydrochloride 1 (30.0 g, 62.1 mmol) was placed in the
round bottom flask and in a vacuum (20 mm Hg), stirred at 190
oC for 30 min to give the crude product, which was purified using
flash silica gel column chromatography (CHCl3/MeOH = 10:1) to
give berberrubine 2 as red solid (25.5 g, 88.4% yield).
16. Synthesis
of
12-((1H-imidazol-1-yl)methyl)-9-hydroxy-10-
methoxy-5,6-dihydro-[1,3]dioxolo[4,5-g]isoquinolino[3,2-a]
isoquinolin-7-ium chloride (3a)
To a solution of imidazole (340.4 mg, 5.0 mmol), formaldehyde
aqueous solution (37%, 0.4 mL, 5.0 mmol) and hydrochloric acid
(catalytic amount) in anhydrous n-butanol (5.0 mL) was added
hydrochloride berberrubine (357.8 mg, 1.0 mmol). The resulting
mixture was stirred at 110 oC for 5 h. After the reaction was
completed (monitored by TLC, chloroform/methanol (10/1,
V/V)), concentrated under reduced pressure to give the crude
product, which was purified using silica gel column
chromatography (chloroform/methanol = 20:1) to give 223.3 mg
of 3a as dark red solid. Yield: 51%; m.p.: > 250 °C; IR (KBr, cm-
1) ν: 3401 (OH), 3140, 3092, 3033 (Ar-H), 2962, 2930 (CH2, CH3)
8.
9.
1
cm-1; H NMR (600 MHz, MeOD) δ 9.22 (s, 1H, 8-H), 7.96 (s,
National Committee for Clinical Laboratory Standards Approved
standard Document, M27-A2, Reference Method for Broth
Dilution Antifungal Susceptibility Testing of Yeasts. National
Committee for Clinical Laboratory Standards, Wayne, PA, 2002.
1H, 13-H), 7.68 (s, 1H, 1-H), 7.45 (s, 1H, Im-H), 7.38 (s, 1H, 4-
H), 7.00 (s, 1H, Im-H), 6.85 (s, 1H, Im-H), 6.76 (s, 1H, 11-H),
5.95 (s, 2H, OCH2O), 5.45 (s, 2H, CH2), 4.52–4.48 (m, 2H, 6-H),
3.80 (s, 3H, OCH3), 3.05–3.01 (m, 2H, 5-H) ppm; 13C NMR (151
MHz, MeOD) δ 164.51, 149.83, 149.39, 148.22, 146.53, 136.88,
135.31, 130.07, 129.80, 127.81, 124.37, 121.44, 120.49, 119.19,
113.69, 110.70, 107.87, 104.70, 101.93, 55.50, 54.04, 46.82,
27.49 ppm; HRMS (ESI) calcd. for C23H20ClN3O4 [M-Cl]+,
402.1448; found, 402.1447.
10. (a) Hunziker, D.; Wyss, P. C.; Angehrn, P.; Mueller, A.; Marty, H.
P.; Halm, R.; Kellenberger, L.; Bitsch, V.; Biringer, G.; Arnold,
W.; Stämpfli, A.; Schmitt-Hoffmannb, A.; Cousot, D. Bioorg.
Med. Chem. 2004, 12, 3503; (b) Zhang, S. L.; Damu, G. L. V.;
Zhang, L.; Geng, R. X.; Zhou, C. H. Eur. J. Med. Chem. 2012, 55,
164; (c) Rackham, M. D.; Brannigan, J. A.; Rangachari, K.;
Meister, S.; Wilkinson, A. J.; Holder, A. A.; Leatherbarrow, R. J.;
Tate, E. W. J. Med. Chem. 2014, 57, 2773; (d) Kügler, F.; Sihver,
W.; Ermert, J.; Hübner, H.; Gmeiner, P.; Prante, O.; Coenen, H. H.
J. Med. Chem. 2011, 54, 8343.