1. Ecofriendly synthesis of carbohydrate-derived heterocycles with potential antiproliferative activity
Verónica Luque-Agudo, María Victoria Gil
IACYS-Unidad de Química Verde y Desarrollo Sostenible, Departamento de Química Orgánica e Inorgánica, Universidad de Extremadura

2. “On water” methodology
Introduction
Energy efficiency
Green
Chemistry
Atom economy
Sustainability
“On water” methodology
Solventless
reactions

3. Introduction
Antimalarial
Antibacterial
Antifungal
Anticancer

4. Introduction
Antihypertensive
Antifungal
Anticoagulant
Antitumor

5. Synthesis of 2-glyco-3-nitro-1,2-dihydroquinolines
1-3 days
59%-92% yield

6. Synthesis of 2-glyco-3-nitroquinolines
1-3 hours
47%-87% yield

7. Synthesis of 2-glyco-3-nitro-2H-chromenes
hours
40%-75% yield

8. Evaluation of their antiproliferative activity
Breast (HBL-100)
Cervix (HeLa)
Non-small cell
lung (A549)
Non-small cell
lung (SW1573)
Breast (T-47D)
Colon (WiDr)

9. GI50 Evaluation of their antiproliferative activity
Compound concentration required to inhibit 50% cell growth
Modified1 SRB protocol2 (NCI, USA)
Cisplatin
5-fluorouracil
Etoposide
1 P. Miranda, J.M. Padrón, J.I. Padrón, J. Villar, V.S. Martin, Chem. Med. Chem. 2006, 1, 323.
2 A. Monks, D. Scudiero, P. Skedan, R. Shoemaker, K. Paull, D. Vistica, C. Hose, J. Langley, P. Cronice, M. Vaigro-Wolf, M. Gary-Goodrich, H. Campbell, M. Mayo, J. Natl. Cancer Inst. 1991, 83, 757.

10. Evaluation of their antiproliferative activity: 1,2-DHQ’s

11. Evaluation of their antiproliferative activity: Q’s

12. Evaluation of their antiproliferative activity: chromenes

13. Evaluation of their antiproliferative activity: chromenes

14. Evaluation of their antiproliferative activity: chromenes

15. Conclusions
New 2-glyco-3-nitro-1,2-DHQ’s, Q’s and 2H-chromenes have been synthesized by using green methodologies: catalysed solventless reactions
In general, 1,2-DHQ’s and Q’s exhibit lower GI50 values than chemotherapeutic reference compounds, except in the cases of 3b, 6b, 13b and 13c against T-47D and WiDr cells
Chromenes show a better antiproliferative profile against all cell lines than the three chemotherapeutic reference compounds, highlighting products 14, 11b and 11e

16. Acknowledgements

17. Ecofriendly synthesis of carbohydrate-derived heterocycles with potential antiproliferative activity
Verónica Luque-Agudo, María Victoria Gil
IACYS-Unidad de Química Verde y Desarrollo Sostenible, Departamento de Química Orgánica e Inorgánica, Universidad de Extremadura

18. Compound
A549
HBL-100
HeLa
SW1573
T-47D
WiDr
GI50 ± sD values(µM) 3a
29 ± 3.2
73 ± 29
33 ± 7.3
67 ± 26
71 ± 25
53 ± 16 6a
70 ± 28
72 ± 26
38 ± 6.9
72 ± 39
>100
90 ± 18
6a-deacet.
13a
56 ± 17
83 ± 23
43 ± 3.1
63 ± 9.7
54 ± 15
56 ± 16 3b
25 ± 9
26 ± 5.3
24 ± 8.3
40 ± 8.5
23 ± 5.6
30 ± 2.9 6b
37 ± 5
26 ± 6
90 ± 0.3
32 ± 0.38
47 ± 13
6b-deacet.
13b
15 ± 1.2
17 ± 0.91
16 ± 2.2
12 ± 2.4
18 ± 3.8
19 ± 3.4 3c
88 ± 17
97 ± 4.6
52 ± 2.3
91 ± 12
93 ± 12
82 ± 24 6c
89 ± 1.9
44 ± 8.1
41 ± 13
82 ± 17
59 ± 8.9
6c-deacet.
29 ± 4.4
32 ± 2.8
32 ± 6.4
54 ± 0.58
50 ± 9.8
49 ± 0.10
13c
31 ± 7.6
15 ± 2.5
28 ± 6.4
26 ± 3.7
Etoposide
0.7 ± 0.2
2.3 ± 0.9
3.0 ± 0.9
15 ± 1.5
22.0 ± 5.5
23.0 ± 2.1
5-fluorouracil
Not tested
5.5 ± 2.3
15 ± 4.7
4.3 ± 1.6
47 ± 18
49 ± 6.7
Cisplatin
2.1 ± 0.6
1.9 ± 0.2
2.0 ± 0.3
3.0 ± 0.4
15.0 ± 2.3
26.0 ± 5.3

19. Compound
A549
HBL-100
HeLa
SW1573
T-47D
WiDr
GI50 ± sD values(µM) 9a
25 ± 8.3
39 ± 14
15 ± 6.2
35 ± 9.9
29 ± 7.7
32 ± 6.5
10a
9.2 ± 5.2
14 ± 4.3
14 ± 2.5
13 ± 2.9
16 ± 5.3
15 ± 3.2 9b
2.5 ± 0.86
2.9 ± 0.25
2.8 ± 0.40
2.4 ± 0.39
3.4 ± 0.19
1.9 ± 0.76 9c
3.0 ± 0.34
2.3 ± 0.055
2.8 ± 0.18
2.4 ± 0.34
3.5 ± 0.013
1.7 ± 0.39 9d
1.3 ± 0.38
2.0 ± 0.41
1.8 ± 0.69
1.0 ± 0.027
2.0 ± 0.53
2.6 ± 0.54
9d-deacet.
63 ± 32
32 ± 3.0
28 ± 3.3
20 ± 0.93
43 ± 11
66 ± 30 9e
7.7 ± 2.4
11 ± 4.4
7.0 ± 0.60
4.3 ± 2.0
16 ± 2.9
21 ± 4.5
9e-deacet.
<100 14
2.2 ± 0.89
3.4 ± 0.45
2.1 ± 0.96
2.0 ± 0.89
3.4 ± 0.98
2.3 ± 1.3 15
39 ± 15
61 ± 16
42 ± 9.8
23 ± 3.2
9b+10b
2.2 ± 0.69
2.7 ± 0.47
2.0 ± 0.80
3.2 ± 0.55
4.1 ± 0.87
9c+10c
1.5 ± 0.28
1.8 ± 0.23
1.5 ± 0.55
0.96 ± 0.064
2.3 ± 0.85
2.7 ± 0.90
9d+10d
1.5 ± 0.72
1.9 ± 0.51
1.5 ± 0.38
1.3 ± 0.57
2.1 ± 0.68
2.4 ± 0.77
12a
32 ± 8.4
60 ± 28
26 ± 4.3
55 ± 16
32 ± 4.1
56 ± 13
11a
23 ± 4.3
27 ± 5.6
23 ± 4.1
23 ± 6.6
28 ± 4.3
11b
1.2 ± 0.19
2.0 ± 1.1
1.5 ± 0.20
1.2 ± 0.25
2.4 ± 0.71
3.1 ± 0.37
11e
2.4 ± 0.69
6.6 ± 3.1
2.7 ± 0.68
2.2 ± 0.29
5.2 ± 2.1
12 ± 1.6 16
22 ± 9.7
32 ± 3.7
24 ± 1.5
20 ± 2.8
18 ± 9.9
65 ± 21 17
58 ± 34
69 ± 7.6
44 ± 12
Etoposide
0.7 ± 0.2
2.3 ± 0.9
3.0 ± 0.9
15 ± 1.5
22.0 ± 5.5
23.0 ± 2.1
5-fluorouracil
Not tested
5.5 ± 2.3
15 ± 4.7
4.3 ± 1.6
47 ± 18
49 ± 6.7
Cisplatin
2.1 ± 0.6
1.9 ± 0.2
2.0 ± 0.3
3.0 ± 0.4
15.0 ± 2.3
26.0 ± 5.3