Concept of Hybrid Drugs and Recent Advancements in Anticancer Hybrids
Abstract
:1. Introduction
2. The Concept of Hybrid Drugs in Anticancer Agent Development
3. Recent Advances in Anticancer Hybrids
3.1. Quinazoline Based Hybrids
Quinazoline-Based Hybrids That Are FDA Approved or under Clinical Trial
3.2. Indole-Based Hybrids
3.3. Indole-Based Hybrids That Are FDA Approved or under Clinical Trial
3.4. Carbazole Based Hybrids
Carbazole-Based Hybrids That Are FDA Approved or under Clinical Trial
3.5. Pyrimidine-Based Hybrids
FDA Approved Pyrimidine Based Hybrids
3.6. Quinoline-Based Hybrids
Quinoline-Based FDA Approved Drugs
3.7. Quinone Hybrids
Quinone Containing FDA Approved Drugs
3.8. Imidazole Based Hybrids
Imidazole Based Hybrids That Are FDA Approved or under clinical Trial
3.9. Selenium-Based Hybrids
Selenium-Based Hybrids That Are FDA Approved or under Clinical Trials
3.10. Platinum-Based Hybrids
Platinum Based Drugs That Are FDA Approved or under Clinical Trial
3.11. Hydroxamic Acid Hybrids
Hydroxamic Acid Based Hybrids That Are FDA Approved or under Clinical Trial
3.12. Ferrocene Hybrids
3.13. Curcumin-Based Hybrids
3.14. Triazole-Based Hybrids
3.15. Benzimidazole-Based Hybrids
Benzimidazole Based Hybrids That Are FDA Approved or under Clinical Trials
3.16. Isatin Containing Hybrids
Isatin Containing FDA-Approved Hybrids
3.17. Pyrrolo-Benzodiazepines Based Hybrids
FDA Approved Drugs Containing Pyrrolo-Benzodiazepines
3.18. Chalcone-Based Hybrids
3.19. Coumarin-Based Hybrids
3.20. Nitrogen Mustard Based Hybrids
3.21. Pyrazole-Based Hybrids
3.22. Pyridine-Based Hybrids
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
EGFR | Epidermal Growth Factor Receptor |
EMA | European Medicines Agency |
FDA | Food and Drug Administration |
HDAC | Histone Deacetylases |
MDR | Multidrug Resistance |
PDGF | Platelet Derived Growth Factor |
SAHA | Suberoylanilide Hydroxamic Acid |
VEGFR-2 | Vascular Endothelial Growth Factor Receptor-2 |
WHO | World Health Organization |
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Compound No. | R1 | R2 | R3 | R4 | n | EGFR (IC50 nM) | HT-29 (IC50 µM) | |
---|---|---|---|---|---|---|---|---|
Normoxia | Hypoxia | |||||||
1b | Cl | F | NO2 | H | 5 | 0.32 | 12.89 | 9.81 |
1c | Br | H | NO2 | H | 2 | 0.66 | 4.48 | 4.01 |
1d | ethynyl | H | NO2 | H | 3 | 0.56 | 10.08 | 5.96 |
1e | ethynyl | H | NO2 | H | 5 | 0.50 | 2.93 | 3.46 |
Gefitinib | 0.45 | 3.63 | 5.21 |
Compound No. | R1 | R2 | R3 | EGFR (IC50 nM) | α-Glucosidase (IC50 µM) |
---|---|---|---|---|---|
2b | 3-Cl, 4-(3-fluorobenzyloxy) | 4.53 | 0.14 | ||
2c | 3-ethynyl | 4.87 | 0.09 | ||
2d | 3-ethynyl | ND * | 6.25 | ||
2e | 3-Cl, 4-F | 10.71 | 4.34 | ||
Gefitinib | 3.32 | ≥100 |
Compound No. | R1 | R2 | X | EGFR (IC50 nM) | VEGFR-2 (IC50 nM) |
---|---|---|---|---|---|
3b | m-Cl, p-F | Cl | 14 | 14 | |
3c | m-CH3, p-CH3 | Cl | 78 | 51 | |
3d | o-CH3 | Cl | 15 | 178 | |
3e | H | Cl | 14 | 261 | |
vandetanib | 11 | 15 |
Compound No. | Ar. | MCF-7 (GI50 μM) | PI3K (IC50 μM) | ||
---|---|---|---|---|---|
A | β | γ | |||
4b | 15 | 5.3 | 16 | 2.3 | |
4c | 12 | 22.2 | 1.9 | 22.2 | |
4d | 12 | 133 | 56 | 5.9 | |
4e | 32 | 14.2 | 0.5 | 14.2 |
Compounds No. | R1 | R2 | X | A549 (µM) | BT549 (µM) | HCT-116 (µM) | MCF-7 (µM) | SK-HEP-1 (µM) | SNU638 (µM) |
---|---|---|---|---|---|---|---|---|---|
5b | 3-COOCH | CH | 1.10 | 1.08 | 0.40 | 10.1 | 2.40 | 1.12 | |
5c | 3-COOCH3-4-Cl | CH | 2.13 | 2.36 | 3.13 | 1.43 | 7.06 | 2.20 | |
5d | 4-OCH3 | CH | 3.58 | 1.88 | 3.49 | 1.79 | 1.61 | 3.97 | |
5e | 2,4-diF | CH | 4.71 | 2.48 | 4.01 | 1.61 | 2.49 | 2.05 | |
Gefitinib | 8.27 | 6.56 | 5.98 | 26.7 | 10.1 | 7.56 | |||
Dactolisib | 0.62 | 0.74 | 0.84 | 1.33 | 1.82 | 1.24 |
Compound No. | R1 | R2 | HCT-116 (µM) | SK-HEP1 (µM) | MDA-MB-231 (µM) | SNU638 (µM) | A549 (µM) | MCF-7 (µM) |
---|---|---|---|---|---|---|---|---|
6b | 1.44 | 4.72 | 0.71 | 0.62 | 0.94 | 1.02 | ||
6c | 0.49 | 0.86 | 0.88 | 1.26 | 3.52 | 4.73 | ||
6d | 0.59 | 0.44 | 0.42 | 0.61 | 1.56 | 10.8 | ||
6e | 1.74 | 1.14 | 2.58 | 0.98 | 3.14 | 4.59 | ||
BEZ235 | 0.84 | 1.82 | 0.18 | 1.24 | 0.62 | 1.33 |
Compound No. | R1 | BRD4 Kd (nM) | MV4-11, IC50 (µM) |
---|---|---|---|
8b | 480 | 4.88 | |
8c | 250 | 2.54 | |
8d | 60 | 5.07 | |
8e | 28 | 1.83 | |
BET760 | - | 37 | 0.80 |
Company Name | Compound Name | Drug Target | Type of Cancer | Status | References |
---|---|---|---|---|---|
AstraZeneca | Vandetanib | Kinase inhibitor | Medullary thyroid cancer | Approved | [33] |
Boehringer Ingelheim | Afatinib | Tyrosine kinase | Non-small cell lung Carcinoma | Approved | [34] |
Pfizer | Dacomitinib | EGFR inhibitor | Non-small cell lung carcinoma | Approved | [10] |
AstraZeneca and Teva | Gefitinib | EGFR inhibitor | Breast and Lung cancer | Approved | [35] |
Roche Pharmaceuticals | Erlotinib | EGFR inhibitor | pancreatic cancer and non-small cell lung cancer | Approved | [36] |
GlaxoSmith Kline (GSK) | Lapatinib | Dual tyrosine kinase inhibitor | solid tumors and Breast cancer | Approved | [37] |
AstraZeneca | Sapitinib (AZD 8931) | Erb8 receptor tyrosine kinase | Breast cancer and metastatic cancer | Clinical trials | [10] |
Array Biopharma | Tucatinib (ARRY 380) | Kinase inhibitor | Breast cancer | Approved | [10] |
Selleck chemicals | Barasertib (AZD 1152) | Aurora Kinase | Tumor lymphoma, solid tumors and myeloid leukemia | Clinical trials | [38] |
Spectrum Pharmaceuticals | Poziotinib | Tyrosine kinase | Breast cancer | Clinical trials | [10] |
AstraZeneca | AZD 3759 | EGFR antagonist | Non-small cell lung Cancer | Clinical trials | [10] |
Curis Inc. | CUDC-101 | By inhibiting Histone deacetylase, EGFR and HER2 | Advanced /Liver/Neck/Gastric/Head/non-small cell lung cancer and Breast | Clinical trials | [39] |
Beta-Phama | Icotinib | EGFR-TK1 inhibitor | Non-small cell lung cancer | Approved | [40] |
Compound No. | R | U937 (µM) | PC-3 (µM) | A549 (µM) | ES-2 (µM) | MDA-MB-231 (µM) | HCT116 (µM) |
---|---|---|---|---|---|---|---|
9b | 3.1 | 10.5 | 11.8 | 29.2 | 7.2 | 6.0 | |
9c | 2.2 | 10.4 | 4.2 | 25.1 | 4.5 | 3.8 | |
9d | 2.2 | 5.8 | 1.6 | 4.4 | 6.8 | 5.9 | |
9e | 2.7 | 5.4 | 7.0 | 8.9 | 7.2 | 2.4 | |
SAHA | - | 2.3 | 9.9 | 3.8 | 12.7 | 5.6 | 6.0 |
Compound No. | R | U937 (µM) | K562 (µM) | HEL (µM) | KG1 (µM) | HL60 (µM) | MDA-MB-231 (µM) | PC-3 (µM) | MCF-7 (µM) | HCT116 (µM) | A549 (µM) |
---|---|---|---|---|---|---|---|---|---|---|---|
10b | 0.33 | 0.79 | 0.20 | 0.39 | 2.11 | 0.24 | 0.33 | 3.47 | 0.37 | 3.39 | |
10c | 0.32 | 0.68 | 0.27 | 0.72 | 1.59 | 0.41 | 0.53 | 2.95 | 0.57 | 3.91 | |
10d | 0.18 | 1.01 | 0.19 | 0.24 | 1.04 | 0.27 | 0.51 | 2.7 | 0.37 | 2.96 | |
10e | 0.34 | 0.89 | 0.16 | 0.47 | 1.68 | 0.15 | 0.29 | 2.32 | 0.22 | 3.27 | |
SAHA | 1.45 | 3.24 | 0.49 | 1.59 | 4.26 | 1.72 | 3.57 | 3.78 | 2.81 | 3.9 |
Compound No. | R1 | R2 | R3 | HeLa Nuclear HDAC (nM) |
---|---|---|---|---|
11b | H | H | 4′-(N-3-hydroxyacrylamide) | 2.8 |
11c | CH3 | H | 4′-(N-3-hydroxyacrylamide) | 3.3 |
11d | CH2CH3 | H | 4′-(N-3-hydroxyacrylamide) | 3.4 |
11e | H | CH3 | 4′-(N-3-hydroxyacrylamide) | 47.4 |
LBH589.HCl | 7.5 |
Compound No. | R1 | R2 | K562 (Upto %) | MDA-MB 231 (µM) | LNCaP (µM) |
---|---|---|---|---|---|
12b | H | 88 | 2 | 32 | |
12c | H | 87 | 28 | 38 | |
12d | F | 64 | 58 | 24 | |
12e | F | 67 | 68 | 35 |
Compound No. | R | PIM (µM) | ||
---|---|---|---|---|
PIM1 | PIM2 | PIM3 | ||
13b | Me2N(CH2)2O | 0.30 | 1.40 | 0.50 |
13c | Et2N(CH2)2O | 0.14 | 0.84 | 0.27 |
13d | Et2N(CH2)3O | 0.11 | 0.38 | 0.081 |
13e | Et2N(CH2)3NH | 0.067 | 3.16 | 0.61 |
Compound No. | R1 | R2 | R3 | A549 (µg/mL) | MCF7 (µg/mL) | SKOV3 (µg/mL) | NIH3T3 (µg/mL) |
---|---|---|---|---|---|---|---|
14b | C2H5 | Br | Me | 4.9 | 50.1 | 68.8 | 52.0 |
14c | H | Br | n-Bu | 8.0 | 54.0 | 74.1 | 141.3 |
14d | Me | OMe | Me | 5.1 | 36.2 | 53.0 | _ |
14e | H | Br | Me | 27.9 | 28.0 | 52.0 | _ |
Etoposide | 7.8 | 9.9 | 8.5 | 118.0 |
Compound No. | R1 | R2 | R3 | HL-60 (µM) | SMMC-7721 (µM) | A-549 (µM) | MCF-7 (µM) | SW480 (µM) |
---|---|---|---|---|---|---|---|---|
15b | Bn | Benzimidazole | 2-Bromobenzyl | 1.21 | 4.69 | 6.76 | 2.23 | 6.35 |
15c | Bn | Benzimidazole | 4-Methylbenzyl | 1.20 | 4.98 | 6.23 | 2.72 | 6.57 |
15d | Bn | 5,6-Dimethyl-benzimidazole | 2-Naphthylmethyl | 1.21 | 2.27 | 4.80 | 1.68 | 1.76 |
15e | Me | 5,6-Dimethyl-benzimidazole | 2-Naphthylmethyl | 1.35 | 4.03 | 6.18 | 1.84 | 4.5 |
DPP | - | - | - | 1.16 | 8.08 | 7.10 | 10.45 | 8.88 |
Compound No. | R1 | R2 | R3 | R4 | R5 | R6 | A549 (µM) | PC3 (µM) | PaCa2 (µM) | |||
---|---|---|---|---|---|---|---|---|---|---|---|---|
24 h | 48 h | 24 h | 48 h | 24 h | 48 h | |||||||
16b | H | H | H | OCH3 | H | H | 9.6 | 5.8 | 33.3 | 12.5 | 27.5 | >50 |
16c | H | OCH3 | H | H | H | H | 6.4 | 7.5 | >50 | 12.0 | 13.5 | >50 |
16d | H | OCH3 | OCH3 | H | H | H | 3.7 | 5.5 | 31.1 | 37.1 | >50 | >50 |
16e | 4.9 | 3.0 | 17.2 | 8.1 | 24.0 | >50 | ||||||
Mitomycin C | 0.45 |
Compound No. | R | MCF-7 (µM) | MDA-MB-231 (µM) |
---|---|---|---|
17b | ≥100 | 71.40 | |
17c | 16.50 | ≥100 | |
17d | 10.99 | 71.40 | |
17e | ≥100 | ≥100 | |
Ospemifene | 55 | 50 | |
Tamoxifen | 3.5 | ≥100 | |
Plumbagin | 75 | 4.4 |
Compound No. | R | MCF-7 (µM) | MDA-MB-231 (µM) |
---|---|---|---|
18b | 50 | >100 | |
18c | >100 | >100 | |
Plumbagin | 3.5 | 4.4 | |
Peganumine A | 38.5 | Not observed | |
Tamoxifen | 50 | 75 |
Company Name | Compound Name | Drug Target | Type of Cancer | Status | Reference |
---|---|---|---|---|---|
AstraZeneca | Cediranib | VEGFR tyrosine kinases | Glioblastoma | Approved | [53] |
Chia-tai Tianqing Pharmaceutical Co. | AL 3818 (Anlotinib) | Tyrosine kinase | Synovial sarcoma, Advanced alveolar soft part sarcoma | Clinical trials | [54] |
Janssen pharmaceuticals | Quisinostat | HDAC inhibitor | Multiple myeloma | Approved | [55] |
Novartis | Panobinostat (LBH-589) | Non-selective HDAC inhibitor | Multiple myeloma | Approved | [56] |
Selleck | Dacinostat (LAQ824) | Histone deacetylase inhibitor | Breast and Prostate cancer | Approved | [57] |
Compound No. | n | R | R’ | HL-60 (µM) | SMMC-7721 (µM) | A549 (µM) | MCF-7 (µM) | SW480 (µM) |
---|---|---|---|---|---|---|---|---|
19b | 2 | Benzimidazole | - | 3.11 | 3.21 | 12.36 | 5.06 | 18.25 |
19c | 2 | imidazole | 4-methylbenzyl | 0.84 | 5.74 | 3.92 | 2.24 | 9.56 |
19d | 2 | benzimidazole | 2-bromobenzyl | 0.71 | 3.66 | 3.58 | 2.14 | 3.08 |
19e | 3 | benzimidazole | 4-methylbenzyl | 0.57 | 2.55 | 2.65 | 2.82 | 3.19 |
DDP | 1.32 | 6.24 | 11.83 | 15.17 | 12.95 |
Company Name | Compound Name | Drug Target | Type of Cancer | Status | References |
---|---|---|---|---|---|
Novartis Pharmaceutical Corporation | Midostaurin | Kinase inhibitor | Advanced systemic mastocytosis, myelodysplastic syndrome | Approved | [67] |
Chugai Pharmaceuticals Co. | Alectinib | Tyrosine kinase | Non-small cell lung cancer | Approved | [68] |
Schwarz Pharma | CEP-2563 | Tyrosine kinase | Solid tumors | Clinical trials | [10] |
Cayman Chemicals | UCN-01 | Tyrosine kinase | Pancreatic, malignant melanoma, ovarian Cancer and small cell lung | Clinical trials | [69] |
Helsinn Healthcare | Becatecarin | Topoisomerase-I | Leukemia and gastric cancer | Clinical Trials | [10] |
Pfizer Pharmaceutical Co. | Edotecarin | Topoisomerase-I | Oesophageal cancer and solid tumors | Clinical trials | [10] |
Compound No. | R | R1 | DNA Displacement Assay (µg/mL) | DNA Binding Affinity |
---|---|---|---|---|
29b | 4-H | 4-Br | 74 | High |
29c | 4-H | 4-NO2 | 81 | weak |
29d | 4-H | 4-OCH3 | 81 | Moderate |
29e | 4-H | 3,4-diOMe | 62 | High |
Ethidium bromide | - | - | 1.4 | - |
Compound No. | R1 | R2 | R3 | CDK9T1 (µM) | CDK1B (µM) | CDK2A (µM) | CDK7H (µM) | HCT-116 (µM) | MCF-7 (µM) |
---|---|---|---|---|---|---|---|---|---|
30b | NH2 | F | m-SO2NH2 | 3 | 7 | 3 | 252 | 0.05 | 0.41 |
30c | NHMe | CN | m-SO2Me | 5 | 19 | 43 | 110 | 0.20 | 0.43 |
30d | NHMe | F | m-SO2NH(CH2)2OCH3 | 3 | 10 | 6 | 30 | 0.30 | 0.72 |
30e | NHMe | CN | p-CO-N-(1-methylpiperidin-4-yl) | 8 | 43 | 32 | 304 | 0.18 | 0.5 |
Compound No. | Ar | R | A-549 (IC50 (µM) | PC-3 |
---|---|---|---|---|
31b | 4-MeC6H4 | COCH3 | 19.33 | 16.92 |
31c | C6H5 | COOC2H5 | 26.64 | 33.56 |
31d | 4-SO2NH2C6H4 | COOC2H5 | 16.42 | 7.15 |
31d | 4-ClC6H4 | COCH3 | 30.56 | 22.90 |
5-FU | 4.21 | 12.00 |
Compound No. | R1 | R2 | U937 (µg/mL) | THP-1 (µg/mL) | Colo205 (µg/mL) |
---|---|---|---|---|---|
32b | H | CH3-(CH2)8-CH2- | 8.16 | 16.91 | 19.25 |
32c | CH3-(CH2)4-CH2- | 6F13-CH2-CH2- | 7.56 | - | 132.42 |
32c | (CH3)2CH- | 8F17-CH2-CH2- | 8.35 | 142.23 | - |
32d | C2H5 | CH3-(CH2)8-CH2- | 17.83 | 82.65 | - |
Etoposide | 17.94 | 2.16 | 7.24 |
Compound No. | R | A549 (µM) | MCF7 (µM) | DU145 (µM) | HeLa (µM) |
---|---|---|---|---|---|
33b | CH3CH2OC(O)CH2- | 16.3 | 12.4 | 18.2 | 9.8 |
33c | CH3(CH2)6CH2- | 5.7 | 24.7 | 6.3 | 22.7 |
33d | CF3(CF2)7CH2CH2- | 33.7 | - | 37.7 | - |
33e | 4.1 | - | 4.7 | - | |
5-FU | - | 1.3 | 1.4 | 1.5 | 1.3 |
Compound No. | R1 | R2 | NCI-H226 (µM) | NPC-TW01 (µM) | Jurkat |
---|---|---|---|---|---|
34b | Ph | p-Me-Ph | 35 | 49 | 48 |
34c | 2-Quinolinyl | p-Cl-Ph | 39 | 35 | 69 |
34d | 2-Quinolinyl | p-OMe-Ph | 37 | 36 | >100 |
34e | Ph | p-Cl-Ph | 18 | 23 | 36 |
N0-(4-formyl-1,3-diphenyl-1H-pyrazol-5-yl)-N,N-dimethyl-methanimidamide | 9.3 | 31.4 | 23.5 |
Company Name | Compound Name | Drug Target | Type of Cancer | Status | Reference |
---|---|---|---|---|---|
Novartis | Ceritinib | Abnormal ALK-gene | Non-Small cell lung Cancer | Approved | [85] |
Pfizer Pharmaceutical company | Palbociclib | CDK4/6 inhibitor | Breast cancer | Approved | [86] |
AbbVie Pharmaceuticals | Ibrutinib | Tyrosine kinase | Mantle cell lymphoma | Approved | [87,88] |
Compounds No. | BALB/3T3 (µM) | A549 (µM) | MCF-7 (µM) | LoVo (µM) | KB (µM) |
---|---|---|---|---|---|
35 | 30.04 | 3.24 | 0.81 | 9.38 | 0.87 |
Doxorubicin | 1.08 | 0.33 | 0.44 | 0.11 | 0.84 |
DiMIQ | 5.77 | 2.19 | 1.54 | 0.20 | 1.14 |
Compound No. | HCT116 (µM) | MCF7 (µM) |
---|---|---|
36 | 16.33 | 27.26 |
Imatinib | 34.40 | - |
Tamoxifien | -- | 34.30 |
Compound No. | R1 | R2 | KB (µM) | A-549 (µM) | MCF-7 (µM) | Hs294T (µM) | BALB/3T3 (µM) |
---|---|---|---|---|---|---|---|
38b | H | 0.15 | 0.81 | 0.79 | 0.64 | 0.67 | |
38c | H | 0.36 | 0.29 | 0.99 | 0.72 | 0.60 | |
38d | H | 0.64 | 0.17 | 0.47 | 0.35 | 0.34 | |
38e | H | 0.08 | 0.19 | 0.66 | 0.76 | 0.57 | |
DIMIQ | 1.14 | 2.19 | 1.50 | 9.70 | 5.70 |
Compound No. | R1 | R2 | MDA-MB-231(µM) | HeLa (µM) | SMMC-7721(µM) | QSG-7701(µM) |
---|---|---|---|---|---|---|
39b | H | CH3 | 1.84 | 1.18 | 17.48 | 40.59 |
39c | OCH3 | CH3 | 1.42 | 0.83 | 17.65 | 45.20 |
39d | F | CH3 | 1.16 | 0.99 | 19.41 | >50 |
39e | H | n-C4H9 | >50 | >50 | >50 | Not tested |
Etoposide | - | - | 5.26 | 2.98 | 3.48 | 28.75 |
Compound No. | R1 | MB231 (GI50 µM) | MB468 (GI50 µM) | MCF-7 (GI50 µM) | 184B5 (GI50 µM) | MCF10A (GI50 µM) |
---|---|---|---|---|---|---|
40b | 2,4-Dinitrophenyl | 24.3 | 19.2 | 10.8 | 37.8 | 35.4 |
40c | 3-Nitrophenyl | 32.2 | 18.6 | 9.4 | 17.7 | 15.4 |
40d | 2,4-Dichlorophenyl | 20.3 | 18.6 | 16.7 | 20.4 | 15.6 |
40e | Biphenyl | 27.2 | 20.5 | 14.8 | 19.1 | 15.5 |
Chloroquine | - | 22.5 | 28.6 | 38.4 | 76.1 | 81.26 |
Cisplatin | - | 23.7 | 31.0 | 25.8 | 25.5 | 51.51 |
Company Name | Compound Name | Drug Target | Type of Cancer | Status | Reference |
---|---|---|---|---|---|
Eisai Co. | Lenvatinib | Kinase inhibitor | Thyroid cancer | Approved | [99] |
Exelixis Inc. | Cabozantinib | Tyrosine-kinase | Thyroid cancer and renal carcinoma | Approved | [68] |
Wyeth and Pfizer | Bosutinib | BCR and Src tyrosine kinase | myelogenous leukemia | Approved | [100] |
Compound No. | R | HeLa (µM) | LS174 (µM) | A549 (µM) | MRC-5 (µM) |
---|---|---|---|---|---|
42b | H | 2.41 | 4.56 | 26.20 | 33.57 |
42c | 2-CH3 | 2.36 | 3.13 | 29.05 | 41.87 |
42d | 3-CH3 | 2.45 | 11.79 | 33.70 | 52.00 |
42e | 4-CH3 | 2.64 | 22.63 | 24.15 | 38.49 |
cisplatin | - | 2.10 | 5.54 | 11.92 | 14.21 |
Compound No. | R | KB (µg/mL) | KB/VCR (µg/mL) | A549 (µg/mL) | HL60 (µg/mL) |
---|---|---|---|---|---|
43b | 4.31 | 2.21 | 6.58 | 4.45 | |
43c | >8.00 | >8.00 | >8.00 | >8.00 | |
43d | >8.60 | 8.52 | 4.49 | 4.46 | |
Vincristine | - | 0.46 | 0.26 | 12.09 | - |
Adriamycin I | - | - | - | - | 0.02 |
Compound No. | R | X | SMMC-7721 (µM) | SW480 (µM) | MCF-7 (µM) | A549 (µM) | HL-60 (µM) |
---|---|---|---|---|---|---|---|
44a | 2-Bromobenzyl | Br | 4.38 | 12.71 | 14.29 | 9.77 | 1.97 |
44b | Phenacyl | Br | 3.71 | 10.34 | 11.90 | 12.94 | 2.61 |
44c | 4-Bromophenacyl | Br | 3.39 | 2.85 | 2.84 | 8.46 | 3.15 |
44d | Naphthyl acyl | Br | 1.65 | 3.38 | 5.87 | 10.93 | 2.49 |
44e | 2′-Phenyl-phenacyl | Br | 3.31 | 6.93 | 6.90 | 6.79 | 2.70 |
DPP | - | - | 8.86 | 15.92 | 16.65 | 11.68 | 1.81 |
Compound No. | R1 | R2 | SMMC-7721 (µM) | SW480 (µM) | MCF-7 (µM) | A549 (µM) | HL-60 (µM) |
---|---|---|---|---|---|---|---|
45a | Benzimidazole | 2-Bromobenzyl | 2.10 | 5.56 | 4.78 | 3.34 | 0.64 |
45b | 2-Ethylimidazole | 4-Hydroxyphenacyl | 11.81 | 5.69 | 3.17 | 12.90 | 0.58 |
45c | 2-Ethylimidazole | 4-Bromophenacyl | 6.07 | 3.58 | 2.89 | 12.76 | 0.72 |
45d | 2-Ethylimidazole | Naphthylacyl | 2.30 | 3.14 | 3.03 | 5.35 | 0.61 |
45e | 2-Ethylimidazole | 2-Bromobenzyl | 0.52 | 0.47 | 0.51 | 0.55 | 0.08 |
DPP | 1.69 | 12.49 | 14.09 | 20.82 | 18.85 |
Compound No. | R | Caco2 (µM) | HCT116 (µM) | HeLa (µM) | MCF-7 (µM) |
---|---|---|---|---|---|
46a | 6.31 | 12.04 | 7.91 | 3.80 | |
46b | 8.45 | 18.32 | 9.45 | 4.45 | |
46c | 4.67 | 16.78 | 6.87 | 0.38 | |
46d | 5.22 | 18.70 | 8.42 | 3.87 | |
46e | 10.87 | 30.98 | 20.34 | 15.56 | |
Doxorubicin | - | 5.17 | 5.64 | 1.25 | 0.65 |
Compound No. | R1 | R2 | R3 | n | MCF-7 (µM) | A549 (µM) | HEPG-2 (µM) | MDA-MB-231 (µM) | LO2 (µM) |
---|---|---|---|---|---|---|---|---|---|
47a | H | CN | CN | 1 | 10.75 | 12.36 | 25.59 | >100 | 49.05 |
47b | H | NO2 | H | 2 | 12.86 | 20.95 | 39.30 | >100 | 46.37 |
47c | H | H | Br | 2 | 12.40 | 26.02 | 41.59 | 80.92 | >100 |
47d |