The michael adducts 2a,b were obtained from the reaction of the phenylacetyl derivative 1 with be... more The michael adducts 2a,b were obtained from the reaction of the phenylacetyl derivative 1 with benzaldehyde and p-anisaldehyde rlaspectively. 2a and 2b were subjected to react with cyanoethanoic acid hydrazide, malonon'itrile, cyanothioacetamide, cyanoacetamide and 1,1,3-tricyano-2-...
In this study, a novel series of 1,2-disubstituted benzo[d]imidazoles was rationally designed as ... more In this study, a novel series of 1,2-disubstituted benzo[d]imidazoles was rationally designed as VEGFR-2 inhibitors targeting hepatocellular carcinoma. Our design strategy is two-fold; it aimed first at studying the effect of replacing the 5-methylfuryl moiety of the well-known antiangiogenic 2-furylbenzimidazoles with an isopropyl moiety on the VEGFR-2 inhibitory activity and the cytotoxic activity. Our second objective was to further optimize the structures of the benzimidazole derivatives through elongation of the side chains at their one-position for the design of more potent type II-like VEGFR-2 inhibitors. The designed 1,2-disubstituted benzimidazoles demonstrated potent cytotoxic activity against the HepG2 cell line, reaching IC50 = 1.98 μM in comparison to sorafenib (IC50 = 10.99 μM). In addition, the synthesized compounds revealed promising VEGFR-2 inhibitory activity in the HepG2 cell line, e.g., compounds 17a and 6 showed 82% and 80% inhibition, respectively, in compariso...
European journal of medicinal chemistry, Jan 25, 2018
Recently a dramatic development of the cancer drug discovery has been shown in the field of targe... more Recently a dramatic development of the cancer drug discovery has been shown in the field of targeted cancer therapy. Checkpoint kinase 2 (Chk2) inhibitors offer a promising approach to enhance the effectiveness of cancer chemotherapy. Accordingly, in this study many pyrimidine-benzimidazole conjugates were designed and twelve feasible derivatives were selected to be synthesized to investigate their activity against Chk2 and subjected to study their antitumor activity alone and in combination with the genotoxic anticancer drugs cisplatin and doxorubicin on breast carcinoma, (ER+) cell line (MCF-7). The results indicated that the studied compounds inhibited Chk2 activity with high potency (IC = 5.56 nM - 46.20 nM). The studied candidates exhibited remarkable antitumor activity against MCF-7 (IG = 6.6 μM - 24.9 μM). Compounds 10a-c, 14 and 15 significantly potentiated the activity of the studied genotoxic drugs, whereas, compounds 9b and 20-23 antagonized their activity. Moreover, the...
European journal of medicinal chemistry, Jan 20, 2018
The development of checkpoint kinase 2 (Chk2) inhibitors for the treatment of cancer has been an ... more The development of checkpoint kinase 2 (Chk2) inhibitors for the treatment of cancer has been an ongoing and attractive objective in drug discovery. In this study, twenty-one feasible pyrazole-benzimidazole conjugates were synthesized to study their effect against Chk2 activity using Checkpoint Kinase Assay. The antitumor activity of these compounds was investigated using SRB assay. A potentiation effect of the synthesized Chk2 inhibitors was also investigated using the genotoxic anticancer drugs cisplatin and doxorubicin on breast carcinoma, (ER+) cell line (MCF-7). In vivo Chk2 and antitumor activities of 8d as a single-agent, and in combination with doxorubicin, were evaluated in breast cancer bearing animals induced by N-methylnitrosourea. The effect of 8d alone and in combination with doxorubicin was also studied on cell-cycle phases of MCF-7 cells using flow cytometry analysis. The results revealed their potencies as Chk2 inhibitors with ICranges from 9.95 to 65.07 nM. General...
European journal of medicinal chemistry, Jan 26, 2017
Inhibition of angiogenesis through inhibition of vascular endothelial growth factor receptor 2 (V... more Inhibition of angiogenesis through inhibition of vascular endothelial growth factor receptor 2 (VEGFR-2) has been applied in cancer therapy because of its important role in promoting cancer growth and metastasis. In the presented study, a series of benzimidazol-furan hybrids was designed and synthesized through facile synthetic pathways. Evaluation of the synthesized compounds for their in vitro cytotoxic activity against breast (MCF-7) and hepatocellular (HepG2) carcinoma cell lines was performed. Two of the synthesized conjugates, 10b and 15, showed potent antiproliferative properties against MCF-7 cell line (IC50 = 21.25, 21.35 μM, respectively) in comparison to tamoxifen (IC50 = 21.57 μM). Additionally, compounds 10a, 10b, 15 and 17 showed promising potency (IC50 = 25.95, 22.58, 26.94 and 31.06 μM, respectively) against liver carcinoma cell line HepG2 in contrast to cisplatin (IC50 = 31.16 μM). Moreover, in vitro evaluation of the synthesized compounds for their effect on the le...
European journal of medicinal chemistry, Jan 14, 2017
Activated checkpoint kinase 2 (Chk2) is a tumor suppressor as one of the main enzymes that affect... more Activated checkpoint kinase 2 (Chk2) is a tumor suppressor as one of the main enzymes that affect the cell cycle. 2-Biarylbenzimidazoles are potent selective class of Chk2 inhibitors; the structure-based design was applied to synthesize a new series of this class with replacing the lateral aryl group by substituted pyrazoles. Ten pyrazole-benzimidazole conjugates from the best fifty candidates according to docking programs have been subjected to chemical synthesis in this study. The activities of the conjugates 5-14 as checkpoint kinase inhibitors and as antitumor alone and in combination with genotoxic drugs were evaluated. The effect of compounds 7 and 12 on cell-cycle phases was analyzed by flow cytometry analysis. Antitumor activity of compounds 7 and 12 as single-agents and in combinations with doxorubicin was assessed in breast cancer bearing animals induced by MNU. The Results indicated that compounds 5-14 inhibited Chk2 activity with high potency (IC50 52.8 nM-5.5 nM). The c...
A series of (benzimidazol-2-yl)-aniline (1) derivatives has been synthesized and evaluated as gly... more A series of (benzimidazol-2-yl)-aniline (1) derivatives has been synthesized and evaluated as glycogen phosphorylase (GP) inhibitors. Kinetics studies revealed that compounds displaying a lateral heterocyclic residue with several heteroatoms (series 3 and 5) exhibited modest inhibitory properties with IC50 values in the 400-600μM range. Arylsulfonyl derivatives 7 (Ar: phenyl) and 9 (Ar: o-nitrophenyl) of 1 exhibited the highest activity (series 2) among the studied compounds (IC50 324μM and 357μM, respectively) with stronger effect than the p-tolyl analogue 8.
European Journal of Medicinal Chemistry, Feb 1, 2010
As a continuation to our previous work in synthesizing antitumor benzimidazoles, a series of 2-((... more As a continuation to our previous work in synthesizing antitumor benzimidazoles, a series of 2-((1Hbenzo[d]imidazol-2-yl)methylthio)-4-(substituted)-6-phenylpyrimidine-5-carbonitriles was synthesized. Evaluation of the synthesized compounds for their in vitro cytotoxic activity against twelve cell lines namely, Cervical carcinoma (KB), Ovarial carcinoma (SK OV-3), CNS cancer (SF-268), Non small lung cancer (NCI H460), Colonadenocarcinoma (RKOP27), Leukaemia (HL60, U937, K562), Melanoma (G361, SK-MEL-28) and Neuroblastoma (GOTO, NB-1) revealed their marked potency when compared with known anticancer drugs.
The benzimidazole starting material 5-(1H-benzo[d]imidazol-2-yl)-4,7-dimethoxybenzofuran-6-ol (2)... more The benzimidazole starting material 5-(1H-benzo[d]imidazol-2-yl)-4,7-dimethoxybenzofuran-6-ol (2)was synthesized. The Mannich bases 3a-k were formed using formaldehyde and primary or secondary amines.(2) was subjected to Mannich reaction using 1,4-phenylenediamine or piperazine to lead to the 1,4-disubstituted benzenes 4a or 1,4-disubstituted piperazines 4b. The compounds were screen for their antimicrobial activities
The world of Benzimidazoles is fascinating. It exhibit multitude of pharmacological activities. H... more The world of Benzimidazoles is fascinating. It exhibit multitude of pharmacological activities. Here, where 2-phenylbenzimidazoles are focused on, the anticancer activities against four different cancer lines are proved. Besides, the molecular docking of the most active compounds into the active site of the target receptor is performed. Keep in mind, the world of Benzimidazoles is endless.
The first crystal structures of four 2-furylbenzimidazole acetohydrazide derivatives are reported... more The first crystal structures of four 2-furylbenzimidazole acetohydrazide derivatives are reported herein. The compounds have been shown to be planar with a small cant that varies from 4 to 30°. The X-ray crystal structure of the compounds 7-10 revealed that compounds are oriented in the cis configuration which suggests that the acid hydrazide group is essential for the enhanced potency of 2-furylbenzimidazoles as anti-angiogenic agents.
The michael adducts 2a,b were obtained from the reaction of the phenylacetyl derivative 1 with be... more The michael adducts 2a,b were obtained from the reaction of the phenylacetyl derivative 1 with benzaldehyde and p-anisaldehyde rlaspectively. 2a and 2b were subjected to react with cyanoethanoic acid hydrazide, malonon'itrile, cyanothioacetamide, cyanoacetamide and 1,1,3-tricyano-2-...
In this study, a novel series of 1,2-disubstituted benzo[d]imidazoles was rationally designed as ... more In this study, a novel series of 1,2-disubstituted benzo[d]imidazoles was rationally designed as VEGFR-2 inhibitors targeting hepatocellular carcinoma. Our design strategy is two-fold; it aimed first at studying the effect of replacing the 5-methylfuryl moiety of the well-known antiangiogenic 2-furylbenzimidazoles with an isopropyl moiety on the VEGFR-2 inhibitory activity and the cytotoxic activity. Our second objective was to further optimize the structures of the benzimidazole derivatives through elongation of the side chains at their one-position for the design of more potent type II-like VEGFR-2 inhibitors. The designed 1,2-disubstituted benzimidazoles demonstrated potent cytotoxic activity against the HepG2 cell line, reaching IC50 = 1.98 μM in comparison to sorafenib (IC50 = 10.99 μM). In addition, the synthesized compounds revealed promising VEGFR-2 inhibitory activity in the HepG2 cell line, e.g., compounds 17a and 6 showed 82% and 80% inhibition, respectively, in compariso...
European journal of medicinal chemistry, Jan 25, 2018
Recently a dramatic development of the cancer drug discovery has been shown in the field of targe... more Recently a dramatic development of the cancer drug discovery has been shown in the field of targeted cancer therapy. Checkpoint kinase 2 (Chk2) inhibitors offer a promising approach to enhance the effectiveness of cancer chemotherapy. Accordingly, in this study many pyrimidine-benzimidazole conjugates were designed and twelve feasible derivatives were selected to be synthesized to investigate their activity against Chk2 and subjected to study their antitumor activity alone and in combination with the genotoxic anticancer drugs cisplatin and doxorubicin on breast carcinoma, (ER+) cell line (MCF-7). The results indicated that the studied compounds inhibited Chk2 activity with high potency (IC = 5.56 nM - 46.20 nM). The studied candidates exhibited remarkable antitumor activity against MCF-7 (IG = 6.6 μM - 24.9 μM). Compounds 10a-c, 14 and 15 significantly potentiated the activity of the studied genotoxic drugs, whereas, compounds 9b and 20-23 antagonized their activity. Moreover, the...
European journal of medicinal chemistry, Jan 20, 2018
The development of checkpoint kinase 2 (Chk2) inhibitors for the treatment of cancer has been an ... more The development of checkpoint kinase 2 (Chk2) inhibitors for the treatment of cancer has been an ongoing and attractive objective in drug discovery. In this study, twenty-one feasible pyrazole-benzimidazole conjugates were synthesized to study their effect against Chk2 activity using Checkpoint Kinase Assay. The antitumor activity of these compounds was investigated using SRB assay. A potentiation effect of the synthesized Chk2 inhibitors was also investigated using the genotoxic anticancer drugs cisplatin and doxorubicin on breast carcinoma, (ER+) cell line (MCF-7). In vivo Chk2 and antitumor activities of 8d as a single-agent, and in combination with doxorubicin, were evaluated in breast cancer bearing animals induced by N-methylnitrosourea. The effect of 8d alone and in combination with doxorubicin was also studied on cell-cycle phases of MCF-7 cells using flow cytometry analysis. The results revealed their potencies as Chk2 inhibitors with ICranges from 9.95 to 65.07 nM. General...
European journal of medicinal chemistry, Jan 26, 2017
Inhibition of angiogenesis through inhibition of vascular endothelial growth factor receptor 2 (V... more Inhibition of angiogenesis through inhibition of vascular endothelial growth factor receptor 2 (VEGFR-2) has been applied in cancer therapy because of its important role in promoting cancer growth and metastasis. In the presented study, a series of benzimidazol-furan hybrids was designed and synthesized through facile synthetic pathways. Evaluation of the synthesized compounds for their in vitro cytotoxic activity against breast (MCF-7) and hepatocellular (HepG2) carcinoma cell lines was performed. Two of the synthesized conjugates, 10b and 15, showed potent antiproliferative properties against MCF-7 cell line (IC50 = 21.25, 21.35 μM, respectively) in comparison to tamoxifen (IC50 = 21.57 μM). Additionally, compounds 10a, 10b, 15 and 17 showed promising potency (IC50 = 25.95, 22.58, 26.94 and 31.06 μM, respectively) against liver carcinoma cell line HepG2 in contrast to cisplatin (IC50 = 31.16 μM). Moreover, in vitro evaluation of the synthesized compounds for their effect on the le...
European journal of medicinal chemistry, Jan 14, 2017
Activated checkpoint kinase 2 (Chk2) is a tumor suppressor as one of the main enzymes that affect... more Activated checkpoint kinase 2 (Chk2) is a tumor suppressor as one of the main enzymes that affect the cell cycle. 2-Biarylbenzimidazoles are potent selective class of Chk2 inhibitors; the structure-based design was applied to synthesize a new series of this class with replacing the lateral aryl group by substituted pyrazoles. Ten pyrazole-benzimidazole conjugates from the best fifty candidates according to docking programs have been subjected to chemical synthesis in this study. The activities of the conjugates 5-14 as checkpoint kinase inhibitors and as antitumor alone and in combination with genotoxic drugs were evaluated. The effect of compounds 7 and 12 on cell-cycle phases was analyzed by flow cytometry analysis. Antitumor activity of compounds 7 and 12 as single-agents and in combinations with doxorubicin was assessed in breast cancer bearing animals induced by MNU. The Results indicated that compounds 5-14 inhibited Chk2 activity with high potency (IC50 52.8 nM-5.5 nM). The c...
A series of (benzimidazol-2-yl)-aniline (1) derivatives has been synthesized and evaluated as gly... more A series of (benzimidazol-2-yl)-aniline (1) derivatives has been synthesized and evaluated as glycogen phosphorylase (GP) inhibitors. Kinetics studies revealed that compounds displaying a lateral heterocyclic residue with several heteroatoms (series 3 and 5) exhibited modest inhibitory properties with IC50 values in the 400-600μM range. Arylsulfonyl derivatives 7 (Ar: phenyl) and 9 (Ar: o-nitrophenyl) of 1 exhibited the highest activity (series 2) among the studied compounds (IC50 324μM and 357μM, respectively) with stronger effect than the p-tolyl analogue 8.
European Journal of Medicinal Chemistry, Feb 1, 2010
As a continuation to our previous work in synthesizing antitumor benzimidazoles, a series of 2-((... more As a continuation to our previous work in synthesizing antitumor benzimidazoles, a series of 2-((1Hbenzo[d]imidazol-2-yl)methylthio)-4-(substituted)-6-phenylpyrimidine-5-carbonitriles was synthesized. Evaluation of the synthesized compounds for their in vitro cytotoxic activity against twelve cell lines namely, Cervical carcinoma (KB), Ovarial carcinoma (SK OV-3), CNS cancer (SF-268), Non small lung cancer (NCI H460), Colonadenocarcinoma (RKOP27), Leukaemia (HL60, U937, K562), Melanoma (G361, SK-MEL-28) and Neuroblastoma (GOTO, NB-1) revealed their marked potency when compared with known anticancer drugs.
The benzimidazole starting material 5-(1H-benzo[d]imidazol-2-yl)-4,7-dimethoxybenzofuran-6-ol (2)... more The benzimidazole starting material 5-(1H-benzo[d]imidazol-2-yl)-4,7-dimethoxybenzofuran-6-ol (2)was synthesized. The Mannich bases 3a-k were formed using formaldehyde and primary or secondary amines.(2) was subjected to Mannich reaction using 1,4-phenylenediamine or piperazine to lead to the 1,4-disubstituted benzenes 4a or 1,4-disubstituted piperazines 4b. The compounds were screen for their antimicrobial activities
The world of Benzimidazoles is fascinating. It exhibit multitude of pharmacological activities. H... more The world of Benzimidazoles is fascinating. It exhibit multitude of pharmacological activities. Here, where 2-phenylbenzimidazoles are focused on, the anticancer activities against four different cancer lines are proved. Besides, the molecular docking of the most active compounds into the active site of the target receptor is performed. Keep in mind, the world of Benzimidazoles is endless.
The first crystal structures of four 2-furylbenzimidazole acetohydrazide derivatives are reported... more The first crystal structures of four 2-furylbenzimidazole acetohydrazide derivatives are reported herein. The compounds have been shown to be planar with a small cant that varies from 4 to 30°. The X-ray crystal structure of the compounds 7-10 revealed that compounds are oriented in the cis configuration which suggests that the acid hydrazide group is essential for the enhanced potency of 2-furylbenzimidazoles as anti-angiogenic agents.
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