Hybrid Molecules Containing a 7-Chloro-4-aminoquinoline Nucleus and a Substituted 2-Pyrazoline with Antiproliferative and Antifungal Activity
Abstract
:1. Introduction
2. Results and Discussion
2.1. Chemistry
2.2. Antiproliferative Activity
2.3. Antifungal Activity
3. Materials and Methods
3.1. General Information
3.2. Synthesis
3.2.1. General Procedure for the Synthesis of the Precursors 1–12
3.2.2. General Procedure for the Preparation of Compounds 15–20
3.2.3. General Procedure for the Preparation of Compounds 21–26
3.2.4. General Procedure for the Preparation of Compounds 27–32
3.2.5. General Procedure for the Preparation of Compounds 33–38
3.3. Antiproliferative Activity
3.4. Antifungal Activity
3.4.1. Microorganisms and Media
3.4.2. Fungal Growth Inhibition Percentage Determination
3.4.3. MIC100, MIC80, and MIC50 Determinations
3.4.4. Statistical Analysis
4. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
References
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R, R′ | Br, H | Cl, H | H, H | OCH3, H | OCH3, OCH3 | CH3, H |
---|---|---|---|---|---|---|
Compound Number and Isolated Yield (%) | 15 (90) | 16 (92) | 17 (83) | 18 (77) | 19 (76) | 20 (86) |
21 (80) | 22 (87) | 23 (73) | 24 (67) | 25 (63) | 26 (70) | |
27 (83) | 28 (81) | 29 (73) | 30 (68) | 31 (65) | 32 (72) | |
33 (75) | 34 (71) | 35 (61) | 36 (47) | 37 (53) | 38 (60) |
Panel Cell Line | Compounds | Doxorubicin (adriamycin) NSC 123127 | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
25 | 30 | 31 | 36 | 37 | 100 µM d | |||||||
GI50 b (µM) | LC50 c (µM) | GI50 (µM) | LC50 (µM) | GI50 (µM) | LC50 (µM) | GI50 (µM) | LC50 (µM) | GI50 (µM) | LC50 (µM) | GI50 (µM) | LC50 (µM) | |
Leukemia | ||||||||||||
CCRF-CEM | 2.50 | >100 | 0.55 | >100 | 6.40 | >100 | 1.84 | >100 | 4.84 | >100 | 0.08 | 100.00 |
HL-60(TB) | 4.68 | >100 | 0.28 | >100 | 5.37 | >100 | 4.78 | >100 | 4.18 | >100 | 0.12 | 89.33 |
K-562 | 0.86 | >100 | 0.49 | >100 | 3.75 | >100 | 2.75 | >100 | 0.76 | >100 | 0.19 | 100.00 |
MOLT-4 | 3.86 | >100 | 0.43 | >100 | 7.98 | >100 | 3.18 | >100 | 3.68 | >100 | 0.03 | 100.00 |
RPMI-8226 | ---- | ---- | 1.27 | 99.1 | 5.33 | >100 | 4.70 | >100 | 3.69 | >100 | 0.08 | 100.00 |
SR | 1.20 | >100 | 1.17 | 89.7 | 5.49 | >100 | 4.29 | >100 | 2.54 | >100 | 0.03 | 100.00 |
Non-small Cell Lung | ||||||||||||
A549/ATCC | 4.15 | >100 | 2.00 | >100 | 8.87 | >100 | 4.70 | >100 | 2.72 | >100 | 0.06 | 100.00 |
HOP-62 | 2.14 | >100 | 0.95 | >100 | 3.81 | >100 | 2.44 | >100 | 1.39 | >100 | 0.07 | 67.61 |
HOP-92 | 1.64 | >100 | 3.93 | >100 | 3.60 | >100 | 10.8 | >100 | 1.85 | >100 | 0.10 | 42.27 |
NCI-H226 | 4.77 | >100 | 11.3 | >100 | 41.2 | >100 | 14.2 | >100 | 8.46 | >100 | 0.05 | 6.40 |
NCI-H23 | 8.82 | >100 | 8.78 | >100 | 64.4 | >100 | 17.5 | >100 | 17.5 | >100 | 0.15 | 13.15 |
NCI-H322M | 13.2 | >100 | 6.39 | >100 | 53.3 | >100 | 15.2 | >100 | 22.2 | >100 | 0.54 | 67.76 |
NCI-H460 | 3.16 | >100 | 0.42 | 47.0 | 3.27 | >100 | 3.04 | >100 | 0.77 | >100 | 0.02 | 51.29 |
NCI-H522 | 1.85 | >100 | 0.95 | 57.0 | 3.60 | >100 | 4.09 | 80.8 | 1.57 | >100 | 0.03 | 2.80 |
Colon Cancer | ||||||||||||
COLO 205 | 3.28 | >100 | 1.43 | 48.5 | 15.7 | >100 | 3.78 | >100 | 3.13 | >100 | 0.18 | 4.33 |
HCC-2998 | 2.09 | >100 | 0.54 | 47.3 | 5.32 | >100 | 3.41 | 80.4 | 3.14 | >100 | 0.26 | 21.68 |
HCT-116 | 3.08 | >100 | 1.12 | 43.3 | 6.51 | >100 | 2.27 | 56.4 | 1.68 | >100 | 0.08 | 54.58 |
HCT-15 | 0.88 | >100 | 0.34 | 57.6 | 2.91 | >100 | 2.30 | >100 | 1.28 | >100 | 6.46 | 100.00 |
HT29 | 2.66 | >100 | ---- | ---- | ---- | ---- | ---- | ---- | ---- | ---- | 0.12 | 67.45 |
KM12 | 1.67 | >100 | 0.23 | >100 | 2.00 | >100 | 0.71 | >100 | 0.82 | >100 | 0.27 | 92.68 |
SW-620 | 2.55 | >100 | 0.28 | 47.1 | 2.44 | >100 | 0.53 | 93.6 | 0.67 | >100 | 0.09 | 58.61 |
CNS Cancer | ||||||||||||
SF-268 | 5.49 | >100 | 4.19 | >100 | 75.5 | >100 | 15.5 | >100 | 8.16 | >100 | 0.10 | 30.48 |
SF-295 | 2.02 | >100 | 1.62 | 60.4 | 3.55 | >100 | 5.80 | 65.2 | 1.71 | >100 | 0.10 | 69.98 |
SF-539 | 1.74 | >100 | 1.15 | 9.23 | 3.08 | >100 | 1.80 | 23.0 | 1.71 | 34.2 | 0.12 | 27.23 |
SNB-19 | 4.91 | >100 | 6.90 | >100 | >100 | >100 | 15.9 | >100 | 30.3 | >100 | 0.04 | 49.77 |
SNB-75 | 1.11 | >100 | 3.34 | >100 | 6.60 | >100 | 12.5 | >100 | 2.22 | >100 | 0.07 | 3.30 |
U251 | 2.91 | >100 | ---- | ---- | ---- | ---- | ---- | ---- | ---- | ---- | 0.04 | 30.62 |
Melanoma | ||||||||||||
LOX IMVI | 1.66 | >100 | 0.34 | 34.8 | 2.30 | >100 | 1.30 | 44.3 | 0.65 | >100 | 0.07 | 50.35 |
MALME-3M | >100 | >100 | 10.7 | >100 | >100 | >100 | 22.7 | >100 | 21.9 | >100 | 0.12 | 3.97 |
M14 | 2.01 | >100 | 0.33 | >100 | 2.60 | >100 | 0.75 | 47.8 | 0.63 | >100 | 0.18 | 4.05 |
MDA-MB-435 | 0.33 | >100 | 0.22 | >100 | 1.47 | >100 | 0.72 | >100 | 0.80 | >100 | 0.25 | 9.57 |
SK-MEL-2 | 2.35 | >100 | 2.07 | >100 | 8.78 | >100 | 11.5 | >100 | 4.65 | >100 | 0.17 | 1.06 |
SK-MEL-28 | 2.66 | >100 | 4.41 | >100 | 10.4 | >100 | 7.07 | >100 | 4.54 | >100 | 0.21 | 15.92 |
SK-MEL-5 | 2.68 | >100 | 1.46 | 18.7 | 4.56 | 96.6 | 3.01 | 33.4 | 1.37 | 18.5 | 0.08 | 0.49 |
UACC-257 | 2.72 | >100 | 1.36 | >100 | 10.5 | >100 | 6.40 | >100 | 3.45 | >100 | 0.14 | 8.15 |
UACC-62 | 1.17 | >100 | 0.05 | 54.9 | 0.87 | >100 | 0.60 | 54.0 | 0.31 | >100 | 0.12 | 0.74 |
Ovarian Cancer | ||||||||||||
IGROV1 | 4.81 | >100 | 11.6 | >100 | 29.2 | >100 | 18.8 | >100 | 3.89 | >100 | 0.17 | 100.00 |
OVCAR-3 | 1.88 | >100 | 3.20 | >100 | 8.64 | >100 | 11.0 | >100 | 3.72 | >100 | 0.39 | 84.33 |
OVCAR-5 | 6.08 | >100 | 11.8 | >100 | >100 | >100 | 15.6 | >100 | 13.2 | >100 | 0.41 | 100.00 |
OVCAR-8 | 4.19 | >100 | 2.85 | >100 | 7.68 | >100 | 5.00 | >100 | 5.36 | >100 | 0.10 | 43.25 |
NCI/ADR-RES | 1.70 | >100 | 1.51 | >100 | 5.97 | >100 | 9.51 | >100 | 3.18 | >100 | 7.16 | 100.00 |
SK-OV-3 | 3.26 | >100 | 9.62 | >100 | >100 | >100 | 15.0 | >100 | 17.3 | >100 | 0.22 | 100.00 |
Renal Cancer | ||||||||||||
786-0 | 2.88 | >100 | 3.95 | >100 | 5.88 | >100 | 2.94 | >100 | 2.05 | >100 | 0.13 | 51.64 |
A498 | 1.66 | >100 | 2.87 | >100 | - | >100 | 4.64 | >100 | 4.65 | >100 | 0.10 | 1.90 |
ACHN | 1.85 | >100 | 3.50 | >100 | 3.52 | >100 | 4.63 | >100 | 1.48 | >100 | 0.08 | 100.00 |
CAKI-1 | 2.12 | >100 | 0.68 | >100 | 2.52 | >100 | 2.38 | >100 | 0.69 | >100 | 0.95 | 100.00 |
RXF 393 | 1.34 | >100 | 8.91 | >100 | 8.37 | >100 | 17.5 | >100 | 2.42 | >100 | 0.10 | 4.69 |
SN12C | 7.56 | >100 | 7.19 | >100 | >100 | >100 | 13.0 | >100 | 7.24 | >100 | 0.07 | 72.44 |
TK-10 | 5.05 | >100 | 3.76 | >100 | 9.57 | >100 | 12.9 | >100 | 3.27 | >100 | 0.18 | 86.70 |
UO-31 | 1.58 | >100 | 0.48 | >100 | 1.68 | >100 | 1.87 | >100 | 0.49 | >100 | 0.49 | 26.18 |
Prostate Cancer | ||||||||||||
PC-3 | 1.47 | >100 | 0.45 | >100 | 1.71 | >100 | 1.18 | >100 | 0.82 | >100 | 0.32 | 87.10 |
DU-145 | 8.08 | >100 | 14.0 | >100 | >100 | >100 | 28.4 | >100 | 17.1 | >100 | 0.11 | 100.00 |
Breast Cancer | ||||||||||||
MCF7 | 0.86 | >100 | 1.52 | >100 | 2.74 | >100 | 3.45 | >100 | 2.31 | >100 | 0.03 | 51.29 |
MDA-MB-231/ATCC | 1.93 | >100 | 1.31 | >100 | 4.77 | >100 | 4.84 | >100 | 2.97 | >100 | 0.51 | 34.75 |
HS 578T | 2.18 | >100 | 6.79 | >100 | 9.22 | >100 | 14.7 | >100 | 2.45 | >100 | 0.33 | 85.70 |
BT-549 | 2.93 | >100 | 7.42 | >100 | 13.9 | >100 | 2.67 | >100 | 4.63 | >100 | 0.23 | 21.33 |
T-47D | 2.13 | >100 | 0.17 | >100 | 1.44 | >100 | 0.70 | >100 | 0.69 | >100 | 0.06 | 85.70 |
MDA-MB-468 | 0.91 | >100 | 2.13 | >100 | 20.1 | >100 | 4.45 | >100 | 6.29 | >100 | 0.05 | 2.52 |
Type | Sub-Type | Compound | Position on Ring A | R | Fungus | MIC100 | MIC80 | MIC50 |
---|---|---|---|---|---|---|---|---|
i | i.1 | 15 | 4 | | Ca | >250 | 250 | 250 |
Cn | >250 | 250 | 125 | |||||
16 | 4 | | Ca | >250 | 250 | 250 | ||
Cn | >250 | 250 | 125 | |||||
17 | 4 | | Ca | >250 | 250 | 250 | ||
Cn | >250 | 250 | 125 | |||||
18 | 4 | | Ca | >250 | 250 | 250 | ||
Cn | >250 | 250 | 250 | |||||
19 | 4 | | Ca | >250 | 250 | 62.5 | ||
Cn | >250 | >250 | 250 | |||||
20 | 4 | | Ca | >250 | 125 | 31.2 | ||
Cn | >250 | 250 | 125 | |||||
i.2 | 21 | 4 | | Ca | >250 | 250 | 62.5 | |
Cn | >250 | 250 | 125 | |||||
22 | 4 | | Ca | >250 | >250 | 250 | ||
Cn | >250 | 250 | 62.5 | |||||
23 | 4 | | Ca | >250 | 62.5 | 31.2 | ||
Cn | >250 | 250 | 250 | |||||
24 | 4 | | Ca | 250 | 250 | 31.2 | ||
Cn | >250 | >250 | >250 | |||||
25 | 4 | | Ca | 250 | 125 | 15.6 | ||
Cn | 62.5 | 31.2 | 15.6 | |||||
26 | 4 | | Ca | >250 | >250 | 250 | ||
Cn | 250 | 125 | 125 | |||||
ii | ii.1 | 27 | 3 | | Ca | 250 | 125 | 62.5 |
Cn | >250 | >250 | 125 | |||||
28 | 3 | | Ca | >250 | 250 | 62.5 | ||
Cn | >250 | >250 | 62.5 | |||||
29 | 3 | | Ca | >250 | >250 | 125 | ||
Cn | >250 | >250 | 250 | |||||
30 | 3 | | Ca | 250 | 250 | 125 | ||
Cn | 250 | 250 | 31.2 | |||||
31 | 3 | | Ca | >250 | >250 | 250 | ||
Cn | >250 | >250 | 250 | |||||
32 | 3 | | Ca | 62.5 | 62.5 | 15.6 | ||
Cn | 31.2 | 15.6 | 7.8 | |||||
ii.2 | 33 | 3 | | Ca | >250 | >250 | 250 | |
Cn | 250 | 250 | 62.5 | |||||
34 | 3 | | Ca | >250 | >250 | >250 | ||
Cn | >250 | 250 | 31.2 | |||||
35 | 3 | | Ca | >250 | 250 | 125 | ||
Cn | >250 | 250 | 62.5 | |||||
36 | 3 | | Ca | 62.5 | 62.5 | 15.6 | ||
Cn | <3.9 | <3.9 | <3.9 | |||||
37 | 3 | | Ca | 125 | 31.2 | 31.2 | ||
Cn | 125 | 62.5 | 31.2 | |||||
38 | 3 | | Ca | 125 | 125 | 62.5 | ||
Cn | 125 | 62.5 | 62.5 | |||||
Amphotericin B | Ca | 1.00 | 0.50 | 0.50 | ||||
Cn | 1.25 | 0.50 | 0.50 |
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Montoya, A.; Quiroga, J.; Abonia, R.; Derita, M.; Sortino, M.; Ornelas, A.; Zacchino, S.; Insuasty, B. Hybrid Molecules Containing a 7-Chloro-4-aminoquinoline Nucleus and a Substituted 2-Pyrazoline with Antiproliferative and Antifungal Activity. Molecules 2016, 21, 969. https://doi.org/10.3390/molecules21080969
Montoya A, Quiroga J, Abonia R, Derita M, Sortino M, Ornelas A, Zacchino S, Insuasty B. Hybrid Molecules Containing a 7-Chloro-4-aminoquinoline Nucleus and a Substituted 2-Pyrazoline with Antiproliferative and Antifungal Activity. Molecules. 2016; 21(8):969. https://doi.org/10.3390/molecules21080969
Chicago/Turabian StyleMontoya, Alba, Jairo Quiroga, Rodrigo Abonia, Marcos Derita, Maximiliano Sortino, Alfredo Ornelas, Susana Zacchino, and Braulio Insuasty. 2016. "Hybrid Molecules Containing a 7-Chloro-4-aminoquinoline Nucleus and a Substituted 2-Pyrazoline with Antiproliferative and Antifungal Activity" Molecules 21, no. 8: 969. https://doi.org/10.3390/molecules21080969
APA StyleMontoya, A., Quiroga, J., Abonia, R., Derita, M., Sortino, M., Ornelas, A., Zacchino, S., & Insuasty, B. (2016). Hybrid Molecules Containing a 7-Chloro-4-aminoquinoline Nucleus and a Substituted 2-Pyrazoline with Antiproliferative and Antifungal Activity. Molecules, 21(8), 969. https://doi.org/10.3390/molecules21080969