Conclusions
Thus, new application has been identified for the
a
tetrahydroquinoline skeleton which is known to have
antitubercular activity. An extension of the tetrahydroquinoline
scaffold has generated 34 new compounds which have handles
for further derivatisation. These compounds, when screened for
neurotrophic activity, showed considerable promise. This opens
up a new application area for these compounds.
Acknowledgements
The authors thank Council of Scientific and Industrial
Research, Department of Science and Technology, Government
of India for research grant. SC thanks Department of Science &
Technology, SERB for a research grant (SB/S2/JCB-002/2015).
Notes and references
1
. a) Frechette, R. PCT Int. Appl.WO 200907350A2 2090611;
b) Schiemann, K.; Finsinger, D.; Amendt, C.; Zenke, F.;
Ger. Offen. DE 102007013855 and PCT Int. Appl. WO
2
008113451; c) Carlso, H. A.; Damm, K. L.; Meagher, K. L.
PCT Int. Appl. WO 2009036341; d) Liu, J.; Wang, Y.; Sun,
Y.; Marshall, D.; Maio, S.; Tonn, G.; Anders, P.; Tocker, J.;
Tang, H. L.; Medina, J. Bioorg. Med. Chem. Lett. 2009, 19,
Figure 3: (a) Protein expression of neurotrophic factors BDNF and NGF in cells treated
with respective compounds at a concentration of 10µM. GAPDH expression was
measured to ensure equal loading protein from different samples.is considered as a
constitutive control. (b) Densitometry of the blots showing fold change in relative
expression of proteins upon differentiation by test compounds.
6
840; e) Russo, E. J. Cannabis. Ther. 2003, 163; f)
Goldfarb, D. S. US 2009163545; g) Ramesh, C.; Nayak, T.
K.; Burai, R.; Dennis, M. K.; Hathway, H. J.; Sklar, L. A.;
Prossnitz, E. R.; Arterburn, J. B. J. Med. Chem. 2010, 53,
Cytotoxicity against
IMR32
Neurotrophic activity
in IMR32
1
004.
2
. a) Pullman, T.; Engendahl, B.; Zhang, Z.; Holscher, M.;
Zanotti-Gerosa, A.; Dyke, A.; Francio, G.; Leitner, L.
Chem.-Eur. J. 2010, 16, 7517; b) Liu, W. B.; He, H.; Dai, L.
X.; You, S. L. Synthesis 2009, 2076; c) Yamashita, K.;
Imahashi, S.; Ito, S. Dyes Pigm. 2008, 76, 748; d) Chen, R.;
Yang, X.; Tian, H.; Sun, L. J. Photochem. Photobiol. A,
S.No MTP No. IC50 (µM) STD DEV Remarks Concentration (µM)
1
2
3
4
5
6
7
8
9
4a
5a
7a
8a
>100
61.57
80.60
>100
>100
17.39
>100
>100
>100
94.67
64.59
>100
>100
66.54
>100
>100
>100
>100
>100
>100
55.99
>100
57.08
87.21
>100
94.37
>100
89.86
>100
>100
64.96
>100
>100
>100
NC
CT
CT
NC
NC
CT
NC
NC
NC
CT
CT
NC
NC
CT
NC
NC
NC
NC
NC
NC
CT
NC
CT
CT
NC
CT
NC
CT
NC
NC
CT
NC
NC
NC
Neurotrophic at10 µM
NN
Neurotrophic at50 µM
Neurotrophic at10 µM
Neurotrophic at10 µM
NN
NN
NN
NN
NN
NN
NN
NN
NN
NN
Neurotrophic at10 µM
NN
NN
NN
Neurotrophic at10 µM
NN
NN
NN
NN
NN
NN
NN
NN
NN
NN
NN
NN
NN
NN
3.65
1.24
2
007, 189, 295; e) Agbo, S. I.; Hallas, G.; Towns, A. D.
9a
Dyes Pigm. 2000, 47, 33; f) Hallas, G.; Zhai, K. Y. Dyes
Pigm. 1996, 32, 187; g) Meier, H. R.; Evans, S. Eur. Pat. EP
10a
11a
4d
4c
5c
11c
8c
9c
10c
4b
11b
8b
9b
10b
5d
1.84
4
97735, 1992; h) Sikhaliev, Kn. S.; Shmyreva,Zh.
V.;Gurova, E. M.;Izv. Vyssh. Uchebn. Zaved, Khim. Khim.
Tekhnol. 1989, 32, 85.
1
0
2.56
2.60
1
1
1
2
1
3
3. a) Rogers, J. L.; Ernat, J. J.; Yung, H.; Mohan, R. S. Catal.
Commun. 2009, 10, 625; b) Reddy, B. V. S.; Srinivas, R.;
Yadav, J. S.; Ramalingam, T. Synth. Commun. 2001, 3,
1
4
1.26
1
5
1
6
1
7
1
075; c) Da Silva-Filbo, L. C.; Lacerda, V.; Jr.,Constantino,
1
8
M. G., Jose da Silva, G. V. Synthesis 2008, 2527; d) Zhou,
Z., Xu, F.; Han, X., Zhou, J.; Qi, J. S. Eur. J. Org. Chem.
1
9
2
0
2
1
8d
9d
2.35
2
007, 5265; e) Sridharan, V.; Avendano, C.; Menendez, J.
2
2
1
1d
4e
11e
0.29
2.37
C. Synthesis 2008, 1039; f) Kamble, V. T.; Ekhe, V. R.;
Joshi, N. S.; Biradar, A. V. Synlett 2007, 1379; g) Semwal,
A.; Nayak,S. Synth. Commun. 2006, 36, 227; h) Yadav, J. S.;
Reddy, B. V. S.;Rao, R. S.; Kumar, S. K.; Kunwar, A. C.
Tetrahedron 2002, 58, 7891; i) Babu, G.; Nagarajan, R.;
Natarajan, R.; Perumal, P. T. Synthesis 2000, 661; j) Babu,
G.; Perumal, P. T. Tetrahedron Lett. 1998, 39, 3225; k)
Duveleroy, D.; Perrio, C.; Parisel, O.; Lasne, M.-L. Org.
Biomol. Chem. 2005, 3, 3794; l) Batey, R. A.; powell, D. A.;
Acton, A.; Lough, A. J. Tetrahedron Lett. 2001, 42, 7935;
m) Ma, Y.; Quim, C.; Xie, M.; Sun, J. J. Org. Chem. 1999,
2
3
2
4
2
5
4f
0.14
0.96
2
6
2
7
11f
5f
2
8
4g
2
9
3
0
11g
1
5
5
6
2a
b
e
a
3.42
3
1
3
2
3
3
34
Table 1- Complete analysis of compounds in the series to determine the cytotoxic
activity (IC50 values±STD DEV) and the neurotrophic activity of compounds.
Doxorubicin was taken as positive control for cytotoxicity against IMR32 cell line and
showed an IC50 value of 8.49±0.04. NOTE: NC-Non Cytotoxic, NN-Non Neurotrophic,
CT-Cytotoxic.
6
4, 6462; n) Makioka, Y.; Shindo, T.; Tamiguchi, Y.; Takai,
K.; Fujiwara,Y. Synthesis 1995, 801; o) Smith, C. D.;
Gavrilyuk, J. L.; Lough, A. J.; Batey, R. A. J. Org. Chem.
2010, 75, 702; p) Gao, K.; Li, Y.; Sun, H.; Fan, R.; Wu,J.
Synth. Commun. 2007, 37, 4425.