Biologically Active Benzimidazole Hybrids as Cancer Therapeutics: Recent Advances
Abstract
1. Introduction
1.1. Cancer
1.2. Benzimidazole
1.3. Biological Activity and Drugs Containing Benzimidazole
2. Benzimidazole Targets and SAR as Anticancer Therapy
2.1. Protein Kinase Inhibitors
2.1.1. Serine/Threonine
CDC-like Kinase
Phosphatidylinositol
Checkpoint Kinase
AMP Kinase
Cyclin-Dependent Kinase
Aurora Kinase
2.1.2. Tyrosine Kinase
HeR2
Estrogen Receptors
EGFR Inhibitors
VEGFR Inhibitors
C-MET-Kinase
2.2. Topoisomerase
2.3. Tubulin Polymerization
2.4. Telomerase Inhibitors
2.5. Apoptotic Proteins
2.5.1. p53
2.5.2. BAX
2.5.3. Caspase-3
2.5.4. Annexin V
2.5.5. Apoptosis Inducers
2.5.6. Poly ADP Ribose Kinase
2.6. Aldose Reductase
2.7. Carbonic Anhydrase
2.8. COX Inhibitors
2.9. CD 133 Antigen
2.10. Drugs Acting on DNA
2.10.1. Circulating Tumor DNA
2.10.2. DNA
2.10.3. Histone Methyltransferase G9a
2.11. Oxidative Stress
2.11.1. Glutathione S-Transferases
2.11.2. Thioredoxin
2.11.3. Mitochondria
2.12. Nedd8 Activating on DNA
2.13. Sirtuin Protein
2.14. Peptidyl Prolyl Isomerase
2.15. F-Actin
3. Conclusions and Future Perspectives
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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CLASS | Structure and Name of the Drug | ||
---|---|---|---|
Anticancer | |||
Antihistamine | |||
Antiparasitic, Anthelmintic | |||
Antihypertensive | |||
Antiviral | |||
Antifungal | |||
PPI | |||
Analgesic | |||
Antiallergic | |||
Antiemetic | |||
uricosuric | |||
Psychopharmacological agent | |||
Anti-dopaminergic, antiemetic, and antipsychotic | |||
Cardiotonic agent |
Cell Line | Compound 1 | Compound 2 | Etoposide |
---|---|---|---|
MCF-7 | 0.092 ± 0.001 | 0.81 ± 0.062 | 2.11 ± 0.024 |
A549 | 0.72 ± 0.042 | 1.90 ± 0.88 | 3.08 ± 0.135 |
Colo-205 | 0.34 ± 0.071 | 0.41 ± 0.12 | 0.13 ± 0.017 |
A2780 | 1.23 ± 0.55 | 1.80 ± 0.59 | 1.31 ± 0.27 |
Compounds | Compound 1 | Compound 2 | ||
---|---|---|---|---|
Binding Energy | Active Site Residues | Binding Energy | Active Site Residues | |
2J5F | −5.22 | Arg841, Asn842, Asp855 | −5.17 | Arg841, Asp855 |
5 × 8I | −7.35 | Phe241, Lys290 | −8.52 | Phe241 |
6FYL | −6.69 | Leu246 | −7.76 | Leu246 |
2WU6 | −7.33 | Lys241, Leu239 | −8.04 | Leu239 |
6FYV | −5.52 | Leu244, Lys191 | −5.42 | None |
5UL1 | −7.84 | Trp850 | −5.69 | Trp850 |
5IZA | −8.15 | None | −7.44 | Lys603, Arg649 |
Z | R | IC50 (µM) |
---|---|---|
-S- | 4-OH | 2.3 ± 0.5 |
-SO2NH- | H | 18 ± 0.8 |
-SO2NH- | 3,4-diCl | 3.4 ± 1.3 |
-O- | H | 55 ± 31 |
-O- | 3,4-diCl | 5.5 ± 1.1 |
-CONH- | H | 410 ± 70 |
-S- | 4-Cl | 8.2 ± 2.0 |
-CONH- | 4-Cl | 680 ± 13 |
-SO2NH- | 4-Cl | 14 ± 4.1 |
-CONH- | 3,4-diCl | >10,000 |
-O- | 4-Cl | 16 ± 6.9 |
Eraselectivity x-Fold Compounds | TR-FRET Erα IC50 (nM) | RBA-Erα (%) | TR-FRET ER β IC50 (nM) | RBA-ERβ (%) | Erα Selectivity x-Fold |
---|---|---|---|---|---|
16 | 6.20 ± 1.52 | 7.52 | 7.89 ± 2.04 | 6.78 | 1.11 |
17 | 11.52 ± 1.53 | 4.04 | 6.09 ± 2.20 | 8.79 | 0.46 |
18 | 7.56 ± 1.57 | 6.17 | 6.69 ± 1.24 | 8.00 | 0.77 |
19 | 0.75 ± 0.94 | 6.91 | 10.8 ± 3.50 | 4.96 | 1.39 |
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Badawy, M.A.S.; Bräse, S.; Ali, T.F.S.; Abdel-Aziz, M.; Abdel-Rahman, H.M. Biologically Active Benzimidazole Hybrids as Cancer Therapeutics: Recent Advances. Pharmaceuticals 2025, 18, 1454. https://doi.org/10.3390/ph18101454
Badawy MAS, Bräse S, Ali TFS, Abdel-Aziz M, Abdel-Rahman HM. Biologically Active Benzimidazole Hybrids as Cancer Therapeutics: Recent Advances. Pharmaceuticals. 2025; 18(10):1454. https://doi.org/10.3390/ph18101454
Chicago/Turabian StyleBadawy, Mohamed A. S., Stefan Bräse, Taha F. S. Ali, Mohamed Abdel-Aziz, and Hamdy M. Abdel-Rahman. 2025. "Biologically Active Benzimidazole Hybrids as Cancer Therapeutics: Recent Advances" Pharmaceuticals 18, no. 10: 1454. https://doi.org/10.3390/ph18101454
APA StyleBadawy, M. A. S., Bräse, S., Ali, T. F. S., Abdel-Aziz, M., & Abdel-Rahman, H. M. (2025). Biologically Active Benzimidazole Hybrids as Cancer Therapeutics: Recent Advances. Pharmaceuticals, 18(10), 1454. https://doi.org/10.3390/ph18101454