Therapeutic Perspective of Vitamin C and Its Derivatives
Abstract
:1. Introduction: Vitamin C and Its Antioxidant and Antitumor Activity
2. Antioxidant Properties of l-Ascorbic Acid Derivatives
2.1. Lipophilic ASA Derivatives with Modified Hydroxyl Groups
2.2. Glucoside ASA Derivatives
2.3. Conjugates of Vitamin C and E
2.4. Butenolide Derivatives
3. Antitumor and Antiviral Activities of l-Ascorbic Acid Derivatives
3.1. Lipophilic ASA Derivatives with Modified Hydroxyl Groups
3.2. Conjugates of ASA Derivative and Pyrimidine and Purine Base
3.3. Conjugates of ASA Derivative and Triazole and Imidazole Moiety
3.4. Conjugates of ASA Derivative and Triterpene
3.5. Butenolide Derivatives
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Comp. | LO Inhibition | Scaveng. of DPPH (%) | Peak Potential (mV) c | |
---|---|---|---|---|
(%) a | IC50 b (μM) | |||
9a, R2 = (CH2)17CH3 | 88 | >90 | 240 | |
10a, R3 = (CH2)11CH3 | 88 | 3.1 | 61 | 300 |
10b, R3 = CH2CO(CH2)9CH3 | 88 | 3.3 | 39 | 380 |
ASA | >90 | 210 |
Comp. | Cytotoxicity | Radical Scaveng. Activity | |
---|---|---|---|
IC50 (×10−5 M) | EC50 (×10−5 M) | IC50/EC50 | |
11a, 6-Laur-ASA-3P | 8.8 | 7.6 | 1.16 |
11b, 6- Myri-ASA-3P | 5.3 | 6.5 | 0.82 |
11c, 6-Palmi-ASA-3P | 4.7 | 6.9 | 0.68 |
11d, 6-Stear-ASA-3P | 4.4 | 7.3 | 0.60 |
Comp. | Scaveng. of DPPH |
---|---|
EC50 (μM) | |
12, 6-Prot-ASA | 0.08 |
13, 6-Gal-ASA | 0.11 |
14, 6-Caf-ASA | 0.20 |
ASA | 0.42 |
Protocatechuic acid | 0.17 |
Gallic acid | 0.10 |
Caffeic acid | 0.17 |
Comp. | Scaveng. of DPPH | |
---|---|---|
(%) | EC50 (×10−5 M) | |
15, ASA-2G | 68.9 | 4.5 |
16, 6-sAcyl-ASA-2G | 69.2–77.5 | 4.1–5.9 |
17, 6-bAcyl-ASA-2G | 3.1–3.7 | |
18, 6-Palmi-ASA | 95.7 | 2.9 |
19, 2,6-Palmi-ASA | 23.7 | |
20, ASA-2P | 1.5 | |
21, ASA-2S | 0.0 | |
ASA | 94.3 | 2.4 |
α-Tocopherol | 90.9 | 1.9 |
Comp. | LO a Inhibition IC50 (μM) |
---|---|
23 | 12 |
24a, 24b | 12 |
24c, 24d | 7 |
ASA | 14 |
α-tocopherol | 37 |
Comp. | EC50/μM | LO a Inhib. | ||
---|---|---|---|---|
OH Inhib. | DPPH Inhib. | Cu2+ b/μM | AAPH b/μM | |
26 | 2 | 16 | 0.1 | 0.18 |
ASA | 30 | 13 | 2.5 | - |
Comp. | Scaveng. of DPPH (%) | Scaveng. of Superoxide Anion |
---|---|---|
27a, R = 2-OCH3-Ph, R4 = H | 55.0 | 58% = IC50 = 3.63 × 10−3 M |
27b, R = 3-OH-Ph, R4 = H | 33.2 | 91% = IC50 = 1.45 × 10−3 M |
27c, R = 2-OH-Ph, R4 = H | 51.1 | NT a |
27d, R = 3-OH-Ph, R4 = 2-OH-Ph | 47.7 | 89% = IC50 = 1.35 × 10−3 M |
ASA | 93.3 | 24% |
Comp. | Scaveng. of DPPH IC50 (μM) | Scaveng. of Superoxide Anion IC50 (μM) | LO a Inhibit. IC50 (μM) |
---|---|---|---|
28a, Ar3 = Ph, Ar4 = 2,3-diOH-Ph | 10.3 | 0.187 | 0.129 |
ASA | 46.6 | 24 | Prooxidant |
Vitamin E | 19.6 | NT b | NT b |
Comp. | EC50 (µg/mL) P388D1 |
---|---|
Ascorbic acid and isomers | 3 |
18, 6-Palmi-ASA | 2 |
31a, ASA-6-stearate (6-Stear-ASA) | 2.5 |
29a, 6-Cl-ASA | 1 |
29b, 6-Br-ASA | 1 |
32a, 3,4-dihydroxytetrone, R5 = H | 3 |
32b, 3,4-dihydroxy-5-methyltetrone, R5 = CH3 | 2 |
32c, 3,4-dihydroxy-5-ethyltetrone, R5 = ethyl | 0.6 |
32d, 3,4-dihydroxy-5-vinylltetrone, R5 = vinyl | 0.35 |
Comp. | IC50 (μM) | |||||
---|---|---|---|---|---|---|
HeLa | MCF-7 | MiaPaCa-2 | Hep2 | SW620 | WI38 | |
34a, R6 = Cl | 17 | 17 | 18 | 17 | 19 | 26 |
IC50 (mM) | ||
---|---|---|
ASA | 36, K873 | |
HuH7 | 1.0 | 0.1 |
HT29 | 1.5 | 0.15 |
Raji | 1.3 | 0.086 |
CCL155 | 2.0 | 0.1 |
Comp. | EC50 (μM) HSV-1 | MNTC a (μM) |
---|---|---|
15 | 16.3 | 1183 |
16g | 4.5 | 86.81 |
ASA | >2270 | 2270 |
Comp. | IC50 (μM) | ||||
---|---|---|---|---|---|
L1210/0 | FM3A/0 | Molt4/C8 | CEM/0 | Hef522 | |
37a, R5 = H | 12.9 | 17.7 | 4.8 | 13.0 | 50 |
37b, R5 = F | 5.1 | 3.4 | 10.9 | 15.1 | 40 |
37c, R5 = Cl | 12.2 | 16.9 | 6.1 | 6.0 | 30 |
37d, R5 = Br | 7.5 | 17.1 | 3.9 | 3.5 | 30 |
37e, R5 = I | 7.5 | 22.6 | 3.9 | 3.3 | 40 |
37f, R5 = CF3 | 2.0 | 3.6 | 0.9 | 1.6 | 60 |
38a, R6 = Cl | 11.6 | 16.4 | 14.8 | 15.9 | 50 |
38b, R6 = pyrrolyl | 110 | >200 | 3.9 | 5.8 | >100 |
39 | 4.1 | 11.4 | 6.8 | 4.4 | 20 |
Comp. | EC50 (μM) | CC50 (μM) | |||||
---|---|---|---|---|---|---|---|
TK+VZV | TK−VZV | CMV | |||||
YS | OKA | 07/1 | YS/R | AD-169 | Davis | ||
37f, R5 = CF3 | 0.5 | 0.3 | 0.5 | 0.3 | >0.5 | 0.4 | 1 |
38b, R6 = pyrrolyl | 1.5 | 1.2 | 2.8 | 0.6 | >0.5 | >0.5 | 4 |
39 | >5 | 5.0 | >5 | 3.8 | >5 | >5 | 20 |
ACV | 0.78 | 0.16 | 17 | 12 | NT a | NT a | >100 |
BVDU | 0.005 | 0.001 | >50 | >50 | NT a | NT a | >100 |
DHPG | NT a | NT a | NT a | NT a | 1 | 5 | >50 |
HPMPC | NT a | NT a | NT a | NT a | 0.11 | 1 | NT a |
IC50 (μg/mL) | ||||
---|---|---|---|---|
L1210/0 | FM3A/0 | Molt4/C8 | CEM/0 | |
41b, R5 = F | 1.4 | 0.78 | 31.8 | 20.9 |
5-FU | 0.04 | 0.02 | 2.9 | 1.2 |
5-FdUrd | 0.0003 | 0.0008 | 2.6 | 0.003 |
Comp. | IC50 (μM) | ||||||||
---|---|---|---|---|---|---|---|---|---|
L1210/0 | Molt4/C8 | CEM/0 | HeLa | MCF-7 | MiaPaCa-2 | Hep-2 | SW 620 | WI 38 | |
(Z)-41b, R5 = F | 5.2 | 118 | 77.4 | 50 | 59.3 | 58.1 | >100 | >100 | 42.6 |
(Z)-41c, R5 = CF3 | >200 | >200 | >200 | 5.6 | 8.8 | 12.8 | 5.6 | 8.8 | 11.6 |
44a, R6 = Cl | 21.8 | 19.8 | 22.9 | 6.8 | 14.3 | 6.5 | 14.8 | 20 | 16.1 |
5-FU | 0.69 | 20 | 9.23 | 16 | 4.5 | 6.5 | 51 | 8.7 | 10 |
ASA | >200 | >200 | >200 | >200 | >200 | >200 | >200 | >100 | >200 |
DiBnASA | 199.4 | 143.2 | 151.7 | >100 | >200 | >100 | >200 | >100 | >100 |
Comp. | IC50 (μM) | ||||||||
---|---|---|---|---|---|---|---|---|---|
L1210 | Molt4/C8 | CEM/0 | HeLa | MCF-7 | MiaPaCa-2 | Hep-2 | SW 620 | WI 38 | |
45a, R5 = propynyl | 0.47 | 0.78 | 0.77 | 0.2 | 0.2 | 0.5 | 0.7 | 0.3 | 0.2 |
45b, R5 = furyl | 6.8 | 6.6 | 7.0 | 2 | 2 | 1.6 | 2.2 | 2.4 | 1.8 |
45c, R5 = vinyl | 7.2 | 7.6 | 7.2 | 14.5 | 3.8 | 22 | 14.2 | 15.6 | 14.3 |
45d, R5 = ethynyl | 6.8 | 7.2 | 4.6 | 3.2 | 2.9 | 8.7 | 4.6 | 5 | 1.5 |
45e, R5 = isopentenyl | 8.2 | 8.3 | 7.7 | 2 | 4 | 5 | 2.6 | 4 | 2 |
46a, R5 = ethynyl-Ph | 8.1 | 8.2 | 7.6 | 2 | 1 | 3 | 3 | 4 | 1 |
Comp. | EC50 (μM) | CC50(μM) Cytotoxicity | ||
---|---|---|---|---|
Sindbis Virus | Coxsackie Virus B4 | Vesicular Stomatitis Virus | ||
45a, R5 = propynyl | 1.6 | 1.6 | 1.6 | 8 |
Ribavirin | 100 | >500 | 100 | >500 |
Comp. | IC50 (μM) | |||||||
---|---|---|---|---|---|---|---|---|
L1210/0 | Molt4/C8 | CEM/0 | HeLa | MiaPaCa-2 | SW 620 | MCF-7 | H-460 | |
47a, R = hexyl | 6.8 | 3.0 | 2.0 | 12 | 3 | 4 | 4 | 2.4 |
47b, R = 4-Br-Ph | 10 | 15 | 7.6 | 8 | 13 | 7 | 21 | 11 |
47c, R = 4-CH3-Ph | 8.7 | 37 | 9.6 | 14 | 21 | 18 | 19 | 23 |
47d, R = 4-butyl-Ph | 8.2 | 9.3 | 8.3 | 4 | 16 | 7 | 17 | 12 |
47e, R = 4-pentyl-Ph | 8.0 | 6.9 | 6.6 | 3 | 10 | 6 | 9 | NT a |
48a, R = butyl | 4.5 | 9.0 | 7.7 | 17 | 15 | 16 | 16 | 16 |
48b, R = 4-Br-Ph | 9.5 | 9.6 | 8.3 | 20 | 14 | 20 | 13 | 16 |
Comp. | EC50 (μM) | Cytotoxicity CC50 (μM) |
---|---|---|
CMV (Davis) | ||
47a, R = hexyl | 1.8 | 10 |
47c, R = 4-CH3-Ph | 3.8 | >20.4 |
Ganciclovir | 2.6 | 262 |
Cidofovir | 0.67 | 133 |
Comp. | IC50 (μM) | |||||
---|---|---|---|---|---|---|
HeLa | MCF-7 | HepG2 | SW 620 | MiaPaCa-2 | WI 38 | |
49a | 7.20 | 2.03 | 1.98 | >100 | 24.24 | 8.49 |
49b | 5.91 | 3.49 | 2.72 | 5.62 | 0.92 | 4.67 |
Comp. | IC50 (μM) | ||||||
---|---|---|---|---|---|---|---|
L1210/0 | CEM/0 | HeLa | MiaPaCa-2 | Hep-G2 | SW620 | 3T3 | |
57 | 4.7 | 4.1 | 12 | 33.9 | >100 | 47.1 | >100 |
(Z, Z)-59 | 4.5 | 19 | 5.6 | 26.2 | >100 | 47.2 | >100 |
5-FU | NT a | NT a | 66.5 | 11.67 | 55.2 | 0.79 | 28.3 |
Comp. | EC50 (μM) HCMV | CC50 (μM) | |
---|---|---|---|
AD-169 | Davis Line | HeLa | |
54a, R1 = R3 = F, R2 = Cl, R4 = CH2Ph | 8.94 | 8.94 | >100 |
Ganciclovir | 6.12 | 4.72 | 328.5 |
Comp. | IC50 (μM) | CC50 (μM) | IC50 (μM) | ||||
---|---|---|---|---|---|---|---|
L1210/0 | P388 | MCF-7 | Molt4/C8 | CEM/0 | Hef522 | TK-VZV (YS/R) | |
60a | 4.52 | 8.12 | 16.87 | 5.97 | 4.71 | 30.47 | 1.62 |
60b | 5.81 | 6.49 | 15.43 | 7.35 | 3.98 | 27.86 | 1.03 |
60c | 6.03 | 7.42 | 14.21 | 6.16 | 5.04 | 32.21 | 0.89 |
61 | 93.35 | 2.67 | >120 | 78.46 | 84.51 | 93.80 | 6.07 |
64c | 1.03 | 0.28 | 0.76 | 1.74 | 0.98 | 17.40 | - |
ara-C | 0.17 | 0.14 | 1.03 | 0.65 | 0.78 | 2.14 × 10−2 | - |
Acyclovir | 4.52 | - | - | - | - | - | 26.43 |
Comp. | E. coli RDPR inhib. (%) a | |
---|---|---|
100 μM | 1000 μM | |
60a | 59.47 | 9.94 |
60b | 58.96 | 11.07 |
60c | 55.34 | 10.20 |
63a | >99 | >99 |
64c | <1 | 0 |
Comp. | LD50 (mg/kg) | IC50 (μg/mL) | |||
---|---|---|---|---|---|
HSV-1 | HIV-1 | HIV-2 | MSV | MT4 | |
66 | 710 | 1.4 | 1.0 | 0.93 | 265 |
67 | - | 6.0 | 7.1 | 0.02 | 14 |
68 | 675 | 4.9 | 4.2 | 13 | >300 |
PMEA | - | 4.1 | 3.8 | 2.0 | 274 |
PMEG | - | 16 | 18 | 0.19 | 16 |
Comp. | IC50 (μM) | EC50 (μg/mL) | CC50 (μg/mL) | |
---|---|---|---|---|
CEM/0 | WI 38 | Hepatitis C | MT4 | |
71a | 10 | >100 | 13.3 | 70.5 |
71b | 7.3 | 73 | >100 | >100 |
Doxorubicin | 0.39 | 0.04 | - | - |
Comp. | EC50 (μM) | CC50 (μM) |
---|---|---|
A/WSN/33 | ||
72b | 8.7 | >200 |
Oseltamivir | 12.5 | >200 |
Comp. | IC50 (μM) | Comp. | IC50 (μM) |
---|---|---|---|
HeLa | HeLa | ||
74a, R = Ph | 3.0 | 75a, R = Ph, R2 = 4-Cl-Ph | 19.7 |
74b, R = 4-Cl-Ph | 2.2 | 75b, R = 4-OCH3-Ph, R2 = 4-Cl-Ph | 4.4 |
74c, R = 2-OH-Ph | 2.9 | 75c, R = Ph, R2 = 4-NO2-Ph | 11.6 |
74d, R = 4-OH-Ph | 2.6 | 75d, R = 4-OCH3-Ph, R2 = 4-NO2-Ph | 11.2 |
74e, R = 4-NO2-Ph | 0.9 | 75e, R = Ph, R2 = 2-furyl | 6.8 |
74f, R = 4-OCH3-Ph | 3.7 | 75f, R = 4-OCH3-Ph, R2 = 2-furyl | 5.1 |
74g, R = 2-furyl | 1.7 | 75g, R = CH3, R2 = 4-Cl-Ph | 8.2 |
74h, R = pyridine-4-yl | 1.3 | 75h, R = 4-OH-Ph, R2 = 4-OCH3-Ph | 7.1 |
74i, R = pyridine-3-yl | 5.6 | 75i, R = Ph, R2 = 4-OH-Ph | 3.7 |
74j, R = 2-furyl | 1.3 | 75j, R = Ph, R2 = 4-Cl-Ph | 4.5 |
74k, R = pyridine-4-yl | 3.0 | 75k, R = 4-OH-Ph, R2 = 4-OCH3-Ph | 6.2 |
74l, R = pyridine-3-yl | 3.4 | 75l, R = CH3, R2 = 2-OH-Ph | 1.8 |
Cisplatin | 2.6 |
Comp. | IC50 (μM) | Comp. | IC50 (μM) | ||
---|---|---|---|---|---|
HeLa | HeLa | ||||
76a, R = | (CH2CH3)2N- | 1.39 | 76f, R = | | 2.43 |
76b, R = | | 24.14 | 76g, R = | | 5.44 |
76c, R = | | 150.03 | 76h, R = | | 15.08 |
76d, R = | | 2.63 | 5-FU | 41.46 | |
76e, R = | | 0.77 |
Comp. | IC50 (μM) |
---|---|
HeLa, A-549, HT-29, HL-60 | |
79b, (3′R) | 3.3–11.1 |
80a, (3′S) | 3.2–4.8 |
80b, (3′R) | 3.3–5.4 |
81a, (3′S) | 2.6–3.5 |
81b, (3′R) | 2.9–3.5 |
82a, (3′S) | 3.0–3.8 |
82b, (3′R) | 2.3–3.8 |
83 | 0.3–3.1 |
Comp. | IC50 (μM) | ||
---|---|---|---|
HeLa | RKO | WI-26 VA4 | |
(Z)-85a, R = 4-N(CH3)2 | 0.26 | 0.48 | 0.65 |
Digoxin | 2.2 | 0.42 | NT a |
Comp. | EC50 (μg/mL) | CC50 (μg/mL) |
---|---|---|
Influenza A (H1N1) | A549; MDCK | |
(E)-86 | 32.3 | >250 |
(Z)-86 | 56.9 | >250 |
87 | 29.1 | >250 |
Ribavirin | 24.6 | |
Zanamivir | 28.4 |
© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
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Meščić Macan, A.; Gazivoda Kraljević, T.; Raić-Malić, S. Therapeutic Perspective of Vitamin C and Its Derivatives. Antioxidants 2019, 8, 247. https://doi.org/10.3390/antiox8080247
Meščić Macan A, Gazivoda Kraljević T, Raić-Malić S. Therapeutic Perspective of Vitamin C and Its Derivatives. Antioxidants. 2019; 8(8):247. https://doi.org/10.3390/antiox8080247
Chicago/Turabian StyleMeščić Macan, Andrijana, Tatjana Gazivoda Kraljević, and Silvana Raić-Malić. 2019. "Therapeutic Perspective of Vitamin C and Its Derivatives" Antioxidants 8, no. 8: 247. https://doi.org/10.3390/antiox8080247
APA StyleMeščić Macan, A., Gazivoda Kraljević, T., & Raić-Malić, S. (2019). Therapeutic Perspective of Vitamin C and Its Derivatives. Antioxidants, 8(8), 247. https://doi.org/10.3390/antiox8080247