Table 1 Correlation between the type of substitution and the exerted mechanism of action
From: Versatile mechanisms of 2-substituted benzimidazoles in targeted cancer therapy
Type of substitution | Mechanism of action | References |
|---|---|---|
1-CH3 2-Aliphatic acid derivative 5- Nitrogen mustard | Alkylating agent | [31, 32] |
1,2-fused 5-Amide 6- CH3 | Alkylating agent | [33] |
2-Acridine | DNA binding agent | [34] |
2-Aromatic 6-Oxindole | DNA binding agent | [35] |
Head to tail bisbenzimidazole 5-Aromatic/piperazine | DNA binding agent | [36] |
1-Aromatic 2-Aromatic 5-Ester | DNA binding agent | [37] |
1,2-Fused | DNA binding agent | [38-40] |
Cu complex with tetrabenzimidazoles | DNA binding agent | [41] |
2-Indole 4-Aromatic | Tubulin inhibitor | [45] |
2-Pyrazole 6-Aliphatic/halogen | Tubulin inhibitor | [46] |
2-Carbamate 5-Se connector/indole | Tubulin inhibitor | [47] |
2-Urea 5-O-linker-Aromatic | Tubulin inhibitor | [48] |
2-Aromatic 4-H/OH/CH3 | Tubulin inhibitor | [49] |
1-Aromatic ketone 2-Aromatic | Tubulin inhibitor | [50] |
1,2-Aromatic 5-Ester | Sirtuin 1&2 inhibitor | [56] |
2-Piperidine 4-Carboxamide | Poly (ADP-ribose) polymerase inhibitor | [58] |
2-Aromatic 4- Carboxamide 5/6-Halogen | Poly (ADP-ribose) polymerase inhibitor | [59, 60] |
2-Aromatic 3,4-Fused | Poly (ADP-ribose) polymerase inhibitor | [61] |
2-CH2-OH 5-NO2 | Methionine synthase inhibitors | [63] |
2-Aromatic amide 5-NO2 | Methionine synthase inhibitors | [64] |
1-Aromatic 2-CH3 6-Triazine | DHFR inhibitor | [67] |
1-Aromatic 2-CH3 6-Hetero-aromatic | DHFR inhibitor | [68] |
2-Aromatic | Topoisomerase I&II inhibitors | [71, 72] |
2-Aromatic 4-Ester | Topoisomerase I&II inhibitors | [73] |
Head to tail bisbenzimidazole 2-Aromatic 5-piperazine | Topoisomerase I&II inhibitors | [74,75] |
Cu comlex 2-Pyridine 5-COOH | Topoisomerase I&II inhibitors | [76] |
1-Aromatic 2-C=O 3-Aliphatic 5-NO2 | Androgen receptor antagonistic activity | [78] |
1-Aromatic 2-Aliphatic 5, 6-Halogen | Androgen receptor antagonistic activity | [79] |
2-Aromatic 5,6-Aliphatic | α-glucosidase inhibitors | [82] |
1,2-Aromatic 5-Amide | G9a Histone Methyltransferase inhibitors | [85] |
1-Hetero-aromatic 2-Aromatic | Pyruvate kinase inhibitors | [88] |
Head to Head bisbenzimidazoles 2-Hetero-aromatic connector 6-Piperazine | Telomerazse inhibitors | [89] |
Tribenzimidazoles 2-Aromatic 6-Piperazine | Telomerazse inhibitors | [90] |
5,6-Fused 2-Cyclic amine/piperazine | Telomerazse inhibitors | [91] |
2-Aromatic | VEGFR-2 inhibitor | [98] |
2-Aromatic 6-Quinoline | VEGFR-2 inhibitor | [92] |
1-Aromatic 2-Furan | VEGFR-2 inhibitor | [99] |
1-Amide/Heteroaromatic 2-Furan | VEGFR-2 inhibitor | [100] |
2-Amide 5,6-Aliphatic | VEGFR-2 inhibitor | [101] |
2-Oxadiazole | EGFR inhibitors | [107] |
1-Aliphatic amine 2-Amide 6-Halogen | EGFR inhibitors | [108] |
2-Indazole 5-Piperazine | FGFR1 inhibitors | [110] |
2-Aromatic ketone 6-Aliphatic | FGFR1 inhibitors | [111] |
2-Pyrrolopyrimidine 5-Sulfonyl/urea | Tie-2 receptor tyrosine kinase inhibitors | [95] |
2-Aromatic 5, 6-Aliphatic | Heparanase inhibitors | [114] |
2-Aromatic | COX1&2 inhibitors | [117] |
2-Pyrazole 5-Aliphatic amine | Aurora A/B kinase inhibitors | [120] |
2-NH-aromatic 5-CF3 | Aurora A/B kinase inhibitors | [121] |
2-Pyrazole 5-Morpholine | Aurora A/B kinase inhibitors | [122] |
1,2-Aliphatic 5-Hetero-aromatic | Aurora A/B kinase inhibitors | [123] |
2-Hetero-aromatic | Checkpoint kinase (Chk1&Chk2) inhibitors | [127] |
2-Hetero-aromatic | Checkpoint kinase (Chk1&Chk2) inhibitors | [128] |
2-Aromatic 5-Amide | Checkpoint kinase (Chk1&Chk2) inhibitors | [129] |
2-Aromatic 5-COOH/Amide | Checkpoint kinase (Chk1&Chk2) inhibitors | [130] |
2-CH3 5-Pyrazole | Checkpoint kinase (Chk1&Chk2) inhibitors | [131] |
2-Aliphatic amines/CF3 4,5,6,7-Halogen | Protein kinase rhCK2α inhibitor | [135, 136] |
2- CF3 4,5,6,7-Halogen | Protein kinase rhCK2α inhibitor | [137] |
2- CH3 4,5,6,7-Halogen | Protein kinase rhCK2α inhibitor | [138] |
2-Pyrazolo-pyridine 4-Aliphatic | Cyclin-dependant kinase (CDK) inhibitors | [140] |
2-Hetero-aromatic 4-Morpholine 7-Aliphatic | Insulin-like growth factor receptor-1 (IFG-1R) inhibitors | [144] |
1-Triazine 2-Halogen | Allosteric Mitogen-Activated Protein Kinase (MEK1) and Phosphatidylinositol 3-Kinase (PI3K) inhibitors | [147] |
2-Hetero-aromatic | allosteric Mitogen-Activated Protein Kinase (MEK1) and Phosphatidylinositol 3-Kinase (PI3K) inhibitors | [148] |
1,2-Aromatic | Farnesyl binding pocket of PDEδ inhibitor | [141] |
1-Triazine 2-CHF2 3-O-linker | Farnesyl binding pocket of PDEδ inhibitor | [143] |
2-Aromatic 6-Quinazolin | Dual c-Met and VEGFR-2 inhibitors | [145] |
2-Hetero-aromatic 6-Piperazine | Multi-target receptor tyrosine kinase inhibitors | [147] |
2-Pyrole 6-Amide | Multi-target receptor tyrosine kinase inhibitors | [148] |
2-Pyrazine 6-Aliphatic amine | Multi-target receptor tyrosine kinase inhibitors | [149] |
1-Aliphatic 2-Aromatic amine | Multi-target receptor tyrosine kinase inhibitors | [149] |