Publications by authors named "Ismail A Abdelhamid"

18 Publications

  • Page 1 of 1

Computational studies and sever apoptotic bioactivity of new heterocyclic cyanoacrylamide based p-fluorophenyl and p-phenolic compounds against liver carcinoma (Hepg2).

Bioorg Chem 2021 Jul 5;114:105147. Epub 2021 Jul 5.

Chemistry Department, Faculty of Science, Cairo University, Giza 12613, Egypt. Electronic address:

An efficient route for the preparation of new heterocyclic cyanoacrylamides based p-fluorophenyl and p-phenolic compounds was depicted. All structures were confirmed based on the different spectral tools and elemental analyses. MTT assay for the novel synthesized series was performed against four different cell lines (A549, MCF7, Hepg2, and Wi38). Among all tested groups, the p-phenolic compound 10 (207.1 µg/ml) and the corresponding p-fluorophenyl derivative 6 (325.7 µg/ml) were selected for further simulation and molecular studies against liver carcinoma. Compounds 6 and 10 were investigated theoretically to different protein sets as (cdk2, Bcl2-xl, cIAP1-BIR3, and MDM2) and they illustrated different binding affinities. The computational studies and different molecular techniques (e.g. cell cycle analysis, DPA assay, relative gene expression, and ELISA assay) were utilized in this report.
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http://dx.doi.org/10.1016/j.bioorg.2021.105147DOI Listing
July 2021

Attacking the mitochondria of colorectal carcinoma by novel 2-cyanoacrylamides linked to ethyl 1,3-diphenylpyrazole-4-carboxylates moiety as a new trend for chemotherapy.

Bioorg Chem 2020 10 26;103:104195. Epub 2020 Aug 26.

Department of Chemistry, Faculty of Science, Cairo University, Giza, Egypt. Electronic address:

A novel set of 2-cyanoacrylamides linked to ethyl 1,3-diphenylpyrazole-4-carboxylates moiety were synthesized and elucidated by different spectroscopic tools. In vitro cytotoxic assay was carried out against different cell lines (Hct, A, MDA-MB, and HFB). Ethyl 5-(2-cyano-3-(furan-2-yl)acrylamido)-1,3-diphenylpyrazole-4-carboxylate 5 achieved the potent cytotoxic effect toward all tested cancer cell lines especially colon cancer (HCT) with IC value (30.6 µg/ml) relative to the lead compound 3 and the standard positive control 5-FU. Additionally, it exhibited less toxic effect toward the normal human melanocytes (HFB4) cell line. Compound 5 was theoretically investigated and compared for its binding affinity to a model of protein markers relative to the lead compound 3 using two different molecular docking programs. More investigations were performed in an attempt to find out the molecular mechanism of this novel compound inside colon cancer cells, as real time PCR analysis, Elisa assay, flow cytometry, and morphological characterizations using TEM and SEM tools.Herein, we showed that compound 5 interferes with the intrinsic pathway of apoptosis at the mitochondrial level in response to an apoptogenic stimulus as cytochromec, caspase-9 and caspases-3 which were triggered by our novel compound 5. All molecular investigations proved that intrinsic apoptotic pathway of colorectal carcinoma was strongly initiated by the effect of compound 5 through upregulation of mitochondrial apoptosis related genes as (Caspase-3, caspase-9, BAX, P, and cytochrome-c) and down-regulated anti-apoptotic proteins (BCL2, MMP1, CDK4, and VEGFR). Further studies proved cell cycle arrest of HCT cell lines at G2/M phase after treatment. In addition, our data revealed that our novel efficiently damage the genomic DNA of colorectal cells involving P dependent mechanism using DPA assay. Sever morphological and ultrastructural changes were detected in colorectal cells treated by compound 5 compared to control using both scanning electron microscopy (SEM) and transmission electron microscopy (TEM).
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http://dx.doi.org/10.1016/j.bioorg.2020.104195DOI Listing
October 2020

Novel [l,2,4]triazolo[3,4-a]isoquinoline chalcones as new chemotherapeutic agents: Block IAP tyrosine kinase domain and induce both intrinsic and extrinsic pathways of apoptosis.

Invest New Drugs 2021 Feb 28;39(1):98-110. Epub 2020 Aug 28.

Department of Chemistry, Faculty of Science, Cairo University, Giza, Egypt.

Two novel chemotherapeutic chalcones were synthesized and their structures were confirmed by different spectral tools. Theoretical studies such as molecular modeling were done to detect the mechanism of action of these compounds. In vitro cytotoxicity showed a strong effect against all tested cell lines (MCF7, A459, HepG2, and HCT116), and low toxic effect against normal human melanocytes (HFB4). The lung carcinoma cell line was chosen for further molecular studies. Real-time PCR demonstrated that the two compounds upregulated gene expression of (BAX, p53, casp-3, casp-8, casp-9) genes and decreased the expression of anti-apoptotic genes bcl2, CDK4, and MMP1. Flow-cytometry indicated that cell cycle arrest of A459 was induced at the G2/M phase and the apoptotic percentage increased significantly compared to the control sample. Cytochrome c oxidase and VEGF enzyme activity were detected by ELISA assay. SEM tool was used to follow the morphological changes that occurred on the cell surface, cell granulation, and average roughness of the cell surface. The change in the number and morphology of mitochondria, cell shrinkage, increase in the number of cytoplasmic organelles, membrane blebbing, chromatin condensation, and apoptotic bodies were observed using TEM. The obtained data suggested that new chalcones exerted their pathways on lung carcinoma through induction of two pathways of apoptosis. Graphical abstract Novel chalcones were prepared and confirmed by different spectral tools. Docking simulations were done to detect the mechanism of action. In vitro cytotoxicity indicated a strong effect against different cancer cell lines and low toxic effects against normal human melanocytes (HFB4). The lung carcinoma cell line was chosen for further molecular studies that include Real-time PCR, Flow-cytometry, Cytochrome c oxidase, and ELISA assay. SEM and TEM tool were used to follow the morphological changes occurred on the cell surface.
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http://dx.doi.org/10.1007/s10637-020-00987-2DOI Listing
February 2021

Novel 2-cyanoacrylamido-4,5,6,7-tetrahydrobenzo[b]thiophene derivatives as potent anticancer agents.

Arch Pharm (Weinheim) 2020 Oct 13;353(10):e2000069. Epub 2020 Jul 13.

Chemistry Department, Faculty of Science, Cairo University, Giza, Egypt.

Ethyl 2-acrylamido-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate as well as its corresponding bis-derivatives, 5-10, with aliphatic linkers were synthesized, fully characterized, and tested as novel anticancer agents. The targeted compounds, 5-10, were obtained by the Knoevenagel condensation reactions of bis-o- or -p-aldehyde with a molar ratio of ethyl 2-(2-cyanoacetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate of 2 in the presence of piperidine in excellent yields (93-98%). The in vitro anticancer activities of the prepared compounds were evaluated against HepG2, MCF-7, HCT-116, and BJ1 cells. Compounds 7 and 9 emerged as the most promising compounds, with IC values of 13.5 and 32.2 µg/ml, respectively, against HepG2 cells, compared with the reference drug doxorubicin (IC : 21.6 µg/ml). Real-time reverse-transcription polymerase chain reaction was used to measure the changes in expression levels of the COL10A1 and COL11A1, ESR1, and ERBB2, or AXIN1 and CDKN2A genes within the treated cells, as genetic markers for colon, breast, or liver cancers, respectively. Treatment of the colon cancer cells with compounds 5, 9, and 10, or breast and liver cancers cells with compounds 7, 8, 9, and 10 downregulated the expression of the investigated tumor markers. The DNA damage values (depending on comet and DNA fragmentation assays) increased significantly upon treatment of colon cancer cells with compounds 5, 9, and 10, and breast and liver cells with compounds 8, 9, and 10. The structure-activity relationship suggested that the increase of the chain of the alkyl linker increases the anticancer activity and the compounds with bis-cyanoacrylamide moieties are more active than those with one cyanoacrylamide moiety.
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http://dx.doi.org/10.1002/ardp.202000069DOI Listing
October 2020

Synthesis, characterization and antimicrobial activity of a novel chitosan Schiff bases based on heterocyclic moieties.

Int J Biol Macromol 2020 Jun 26;153:492-501. Epub 2020 Feb 26.

Chemistry Department, Faculty of Science, Cairo University, Cairo 12613, Egypt. Electronic address:

Three heteroaryl pyrazole derivatives; namely 1-phenyl-3-(thiophene-2-yl)-1H-pyrazole-4-carbaldehyde, 1-phenyl-3-(furan-2-yl)-1H-pyrazole-4-carbaldehyde and 1-phenyl-3-(pyridine-3-yl)-1H-pyrazole-4-carbaldehyde were synthesized and reacted with chitosan to form Schiff bases of chitosan. All newly synthesized compounds have been characterized by solubility tests, elemental analysis, spectral (FTIR, H NMR) analyses, thermogravimetric analysis and X-ray diffraction (XRD). The Schiff bases were screened for their biological activity against gram-negative bacteria (Escherichia coli and Klebsiella pneumonia), gram-positive bacteria (Staphylococcus aureus and Streptococcus mutans) and fungi (Asperagillus fumigatus and Candida albican). The results indicated that the antimicrobial activity was dependent on the type of the Schiff base moiety. Cytotoxicity of the prepared chitosan derivatives was evaluated by MTT assay and the results indicated the absence of cytotoxic activity.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.02.302DOI Listing
June 2020

Molecular Docking Study, Cytotoxicity, Cell Cycle Arrest and Apoptotic Induction of Novel Chalcones Incorporating Thiadiazolyl Isoquinoline in Cervical Cancer.

Anticancer Agents Med Chem 2020 ;20(1):70-83

Chemistry Department, Faculty of Science, Cairo University, Giza, 12613, Egypt.

Background: Chalcones are naturally occurring compounds found in various plant species which are widely used for the traditional popular treatments. Chalcones are distinguished secondary metabolites reported to display diverse biological activities such as antiviral, antiplatelet, anti-inflammatory, anticancer, antibacterial and antioxidant agents. The presence of a,ß-unsaturated carbonyl group in chalcones is assumed to be responsible for their bioactivity. In addition, heterocyclic compounds having nitrogen such as isoquinolines are of considerable interest as they constitute the core structural element of many alkaloids that have enormous pharmacological activities.

Objective: The objective of this study is the synthesis and biological activity of novel chalcones incorporating thiadiazolyl isoquinoline as potential anticancer candidates. Different genetic tools were used in an attempt to know the mechanism of action of this compound against breast cancer.

Methods: An efficient one pot synthesis of novel chalcones incorporating thiadiazolyl isoquinoline was developed. The cytotoxic activity of the novel synthesized compounds was performed against four different kinds of cancer cell lines.

Results: Among all the tested derivatives, chalcone 3 has the best cytotoxic profile against A549, MCF7, and HeLa cell lines, with IC50s 66.1, 51.3, and 85.1μM, respectively. Molecular docking studies for chalcone 3 revealed that CDK2, and EGFRTK domains have strong binding affinities toward the novel chalcone 3, while tubulin-colchicine-ustiloxin, and VEGFRTK domains illustrated moderate mode of binding.

Conclusion: We have developed an efficient method for the synthesis of novel chalcones incorporating thiadiazolyl isoquinoline. All compounds showed better cytotoxicity results against four kinds of cancer cell lines (A549, MCF7, HCT116, and HELA cells). The results depicted that chalcone 3 has a high and promising cytotoxic effect against HELA cell line and the mechanism of cytotoxicity was widely studied through different theoretical and experimental tools. Thus, the newly synthesized derivative 3 can be utilized as a novel chemotherapeutic compound for cervical carcinoma.
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http://dx.doi.org/10.2174/1871520619666191024121116DOI Listing
January 2021

Synthesis, Cytotoxicity and Molecular Docking Simulation of Novel bis-1,4-Dihydropyridines Linked to Aliphatic or Arene Core via Amide or Ester-Amide Linkages.

Mini Rev Med Chem 2020 ;20(9):801-816

Chemistry Department, Faculty of Science, Cairo University, Giza, Egypt.

Objective: Novel bis(1,4-dihydropyridine-3,5-dicarbonitrile) derivatives linked to aliphatic or aromatic cores via amide or ester-amide linkages were prepared and their structures were confirmed by several spectral tools.

Methods: The synthesis of novel N,N'-(alkanediyl)bis(2-(2-(3,5-dicyano-2,6-dimethyl-1,4-dihydropyridin- 4-yl)phenoxy)acetamide) by acid-catalyzed condensation of the bis-aldehydes with four equivalents of 3-aminocrotononitrile was reported.

Results: The structures of the synthesized compounds were confirmed by different spectral tools. The molecular docking stimulation studies indicated that the prepared compounds bind to the active site of cellular inhibitor apoptotic protein (cIAP1-BIR3). MTT assay for the novel bis(1,4-dihydropyridines) was performed on two different human cell lines (A549 and HCT116).

Conclusion: Compound 5a showed higher cytotoxic activity against A549. Compound 5d showed moderate activity against HCT116. The rest of compounds indicated lower or no activity against both cell lines.
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http://dx.doi.org/10.2174/1389557519666190919160019DOI Listing
January 2021

Leaves Extracts Induce Apoptosis and Cell Cycle Arrest of Hepatocellular Carcinoma.

Biomed Res Int 2019 1;2019:2698570. Epub 2019 Jan 1.

Department of Chemistry, Faculty of Science, Cairo University, 12613 Giza, Egypt.

Moringa grows in the tropical and subtropical regions of the world. The genus belongs to family Moringaceae. It is found to possess various medicinal uses including hypoglycemic, analgesic, anti-inflammatory, hypolipidemic, and antioxidant activities. In this study, we investigated the antimicrobial and the anticancer activity of the as well as leaves extracts grown locally in Egypt. Results indicated that most of the extracts were found to possess high antimicrobial activity against gram-positive bacteria, gram-negative bacteria, and fungus. The survival rate of cancer cells was decreased in both hepatocellular carcinoma (HepG2) and breast carcinoma (MCF-7) cell lines when treated with leaves extracts. In addition, the cell cycle progression, apoptosis, and cancer-related genes confirmed its anticancer effect. The toxicity of each extract was also tested using the normal melanocytes cell line HFB4. The toxicity was low in both and leaves extracts. Furthermore, GC/MS analysis fractionized the phytochemicals content for each potential extract. In conclusion, results suggested that the and leaves extracts possess antimicrobial and anticancer properties which could be attributed to the bioactive phytochemical compounds present inside the extracts from this plant. These findings can be used to develop new drugs, especially for liver cancer chemotherapy.
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http://dx.doi.org/10.1155/2019/2698570DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6332967PMC
May 2019

Recent Synthetic Approaches and Biological Evaluations of Amino Hexahydroquinolines and Their Spirocyclic Structures.

Anticancer Agents Med Chem 2019 ;19(7):875-915

Chemistry Department, Faculty of Science, Cairo University, Giza, Egypt.

In this review, the recent synthetic approaches of amino hexahydroquinolines and their spirocyclic structures were highlighted. The synthetic routes include, two-components, three-components or fourcomponents reactions. The two-component [3+3] atom combination reaction represents the simplest method. It involves Michael addition of the electron rich β-carbon of β-enaminones to the activated double bond of cinnamonitriles followed by cyclization to yield hexahydroquinoline compounds. The bioactivity profiles and SAR studies of these compounds were also reviewed with emphasis to the utility of these substances as antimicrobial, anticancer and antitubercular agents, as well as calcium channel modulators.
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http://dx.doi.org/10.2174/1871520619666190131140436DOI Listing
February 2020

Molecular Studies on Novel Antitumor Bis 1,4-Dihydropyridine Derivatives Against Lung Carcinoma and their Limited Side Effects on Normal Melanocytes.

Anticancer Agents Med Chem 2018 ;18(15):2156-2168

Chemistry Department, Faculty of Science, Cairo University, Giza, Egypt.

Background: Cancer is a complex genetic disease which is characterized by an abnormal cell growth, invasion and spreading to other parts of the body. There are several factors that lead to cancer by causing DNA damage and the impairment of its repair. Treatment of cancer using the chemotherapeutic drugs have adverse side effects such as toxicity as they lose their specificity toward cancer cells and affect also normal cells. Moreover, the cancer cells can resist the chemotherapeutic agents and make them ineffective. For these reasons, much attentions have been paid to develop new drugs with limited side effects on normal cells and to diminish cancer resistance to drug chemotherapy. Recently, some 1,4-dihydropyridine derivatives were reported to act as Multi-Drug Resistance (MDR) modulators that inhibit p-glycoprotein which is responsible for the inability of drugs to enter the cancer cells. Also 1,4-DHPs have antimutagenic properties against chemicals via modulating DNA repair when studied on drosophila.

Objective: The objective of this study is the synthesis of bis 1,4-DHPs incorporating ester as well as ether linkages and evaluate the anticancer activity of new compounds for synergistic purpose. Different genetic tools were used in an attempt to know the mechanism of action of this compound against lung cancer.

Method: An efficient one pot synthesis of bis 1,4-DHPs using 3-aminocrotononitrile and bis(aldehydes) has been developed. The cytotoxic effect against human cell lines MCF7, and A549 cell lines was evaluated.

Results: All compounds exhibited better cytotoxicity toward lung carcinoma cells than breast cancer cells. With respect to lung carcinoma cell line (A549), compound 10 was the most active compound and the three other compounds 7, 8, and 9 showed comparable IC values. In case of breast cancer cell line (MCF7), the most active one was compound 7, while compound 8 recorded the least activity.

Conclusion: we have developed an efficient method for the synthesis of novel bis 1,4-dihydropyridine derivatives incorporating ester or ether linkage. All compounds showed better cytotoxicity results against A549 than MCF7, so that lung carcinoma cell line was chosen to perform the molecular studies on it. The results showed that all compounds (7, 8, 9 and 10) caused cell cycle arrest at G1 phase. The molecular docking study on CDK2 confirmed the results of cell cycle assay which showed good binding energy between the compounds and the active site of enzyme indicating the inhibition of the enzyme.
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http://dx.doi.org/10.2174/1871520618666181019095007DOI Listing
August 2019

Synthesis, Cytotoxicity, Antimicrobial and Docking Simulation of Novel Pyrazolo[3,4-d]pyrimidine and pyrazolo[4,3-e][1,2,4]triazolo[3,4-c] pyrimidine Derivatives.

Mini Rev Med Chem 2019 ;19(8):657-670

Department of Chemistry, Faculty of Science, Cairo University, Giza 12613, Egypt.

Background: Isobutyrohydrazonoyl bromide 1 was used as a precursor for the synthesis of 4-imino-3-isopropyl-1-(4-nitrophenyl)-1,4-dihydro-5H-pyrazolo[3,4-d]pyrimidin-5-amine 4, which was converted into hydrazino derivative 5 by heating with hydrazine hydrate at reflux. Hydrazino, as well as imino-amino derivatives, underwent condensation and cyclization reactions to give pyrazolo[ 3,4-d]pyrimidine and pyrazolo[4,3-e][1,2,4]triazolo[3,4-c]pyrimidine derivatives, respectively.

Method: Antimicrobial studies are performed using two-gram positive bacteria and two-gram negative bacteria.

Results: Data revealed that compound 9a is the most promising antibacterial agent with high efficiency (low MIC value (48 μg/ml)). The cytotoxic assay was investigated for in vitro antitumor screening against Caucasian breast adenocarcinoma MCF7, hepatocellular carcinoma HepG2 and colon carcinoma HCT-116 cell lines.

Conclusion: The results are compared with doxorubicin standard anticancer drugs as well as normal cell lines like MCF10 and MCF12. Molecular docking was carried out for the highest potent compound 8c with the binding site of dihydrofolate reductase enzyme DHFR PDB:ID (1DLS).
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http://dx.doi.org/10.2174/1389557518666181017162459DOI Listing
June 2019

Cytotoxicity, molecular modeling, cell cycle arrest, and apoptotic induction induced by novel tetrahydro-[1,2,4]triazolo[3,4-a]isoquinoline chalcones.

Eur J Med Chem 2018 Jan 21;143:532-541. Epub 2017 Nov 21.

Department of Chemistry, Faculty of Science, Cairo University, Giza, Egypt. Electronic address:

Novel tetrahydro-[1,2,4]triazolo[3,4-a]isoquinolin-3-yl)-3-arylprop-2-en-1-one derivatives were synthesized and their structures were confirmed by different spectral tools. Cytotoxicity test revealed that some compounds exhibited strong to moderate effect, while others showed weak action against different cancer cell lines (MCF7, A549, HCT116, and Hepg2). Breast carcinoma revealed higher sensitivity toward all derivatives especially compounds 5 and 8 which offered the lowest IC values (50.05, and 27.15 μg/ml) respectively, relative to the positive control 5-fluorouracil (5-FU) (IC = 178 μg/ml). In addition, the two compounds exhibited less toxic effect toward normal melanocytes (HFB4). Several theoretical and experimental studies were done to reveal the molecular mechanisms that control breast carcinoma metastasis using the two promising novels 5 and 8. Docking simulation studies against the two proteins EGFR and DHFR demonstrate that compound 8 showed higher binding affinity toward the two proteins more than compound 5, suggesting that trimethoxy groups may be responsible for this higher activity through the formation of five hydrogen bonding with the active domain (4r3r) and other four interactions with the active domain (1dls). Real time PCR assay illustrates that the two compounds up regulated BAX, p53, caspase-3 genes and down regulated BCL2, MMP1, CDK4 ones. In addition, it was noted that compound 8 was more effective in gene regulation and apoptotic induction than compound 5. Also, flow cytometer analysis demonstrates that both compounds 5 and 8 induced cell growth arrest at G1 phase and thus, inhibit G1/S transition and cell cycle progression. In addition, both compounds stimulate apoptotic death of breast cells significantly to reach 8.72%, and 17.28% respectively, compared to their control (0.55%). Apoptotic induction of breast cells was enhanced effectively through activation of caspase-3 by compound 8 using Elisa assay.
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http://dx.doi.org/10.1016/j.ejmech.2017.11.045DOI Listing
January 2018

DNA Fragmentation, Cell Cycle Arrest, and Docking Study of Novel Bis Spiro-cyclic 2-oxindole of Pyrimido[4,5-b]quinoline-4,6-dione Derivatives Against Breast Carcinoma.

Curr Cancer Drug Targets 2018 ;18(4):372-381

Chemistry Department, Faculty of Science, Cairo University, Giza, Egypt.

Background: Recently, it is reported that heterocycles containing pyrimidoquinoline moiety show a broad spectrum of medicinal and pharmacological properties including anticancer, anti-microbial, anti-inflammatory activities, analgesic and antiviral. In additions, spirocyclicoxindole containing compounds represent an important class of compounds that exhibit wide range of biological properties. The asymmetric chiral spiro carbon is considered to be the main criteria of the bioactivities. Spirooxindole structures represent the main skeleton for various alkaloids and pharmaceutically important compounds. Among them, the naturally occurring pyrrolidinylespirooxindole alkaloid, horsifiline that exhibits anticancer activity against human brain cancer cell lines.

Objective: The objective of this study is the synthesis of novel bis spiro-cyclic 2-oxindole of pyrimido[4,5-b]quinoline derivatives and evaluate the anticancer activity of new compounds for synergistic purpose. Different genetic tools were used in an attempt to know the mechanism of action of this compound against breast cancer.

Method: An efficient one pot synthesis of bis spiro-cyclic 2-oxindole derivatives of pyrimido[4,5- b]quinoline-4,6-dione using 6-aminouracil, bis-isatin and dimedone has been developed. The cytotoxic effect against different human cell lines MCF7, HCT116 and A549 cell lines was evaluated. The derivative 6a, was found the most encouraging compound in this series and it was selected for molecular studies against MCF7.

Results: Our data indicated that compound 6a is an attractive target for breast cancer, as it inhibits proliferation, cell cycle progression and induces apoptosis of tumor cells. This inhibition is mediated by fragmentation of genomic DNA, up-regulation of [caspase-3, tumor suppressor gene p53, and pro-apoptotic gene BAX], and down-regulation of anti-apoptotic BCL2 gene. In additions it caused cell cycle arrest in S phase. This work provides an evidence of the potent effect of the new compound 6a and assists in the progress of new healing agents for cancer.

Conclusion: We have developed an efficient method for the synthesis of novel bioactive bis spirocyclic 2-oxindole derivatives incorporating pyrimido[4,5-b]quinoline derivatives. Most of our new derivatives give potent cytotoxic effect more than the standard drug Fluorouracil (5-FU) especially, compound 6a which was the most active and promising one in this series against MCF7, HCT116, and A549 cell lines.
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http://dx.doi.org/10.2174/1568009617666170630143311DOI Listing
June 2019

Apoptotic induction mediated p53 mechanism and Caspase-3 activity by novel promising cyanoacrylamide derivatives in breast carcinoma.

Bioorg Chem 2017 08 1;73:43-52. Epub 2017 Jun 1.

Chemistry Department, Faculty of Science, Cairo University, Giza, Egypt. Electronic address:

New cyanoacrylamide derivatives were theoretically examined for their binding abilities to a protein model of apoptosis inhibitor proteins x-IAP and c-IAP1 using molecular modeling. The two compounds 5a and 5b proved promising IAP antagonists, where they have good binding affinity toward the selected active domains. Anticancer activity of all derivatives was performed on different human cancer cell lines (HCT116, Caco, and MCF7) as well as normal line (HBF4). Data revealed that breast carcinoma was more sensitive to the novel compounds than other lines especially compounds 5a and 5b, but all derivatives lost their cytotoxic effect in case of Caco2 cell line and they showed low cytotoxic effect toward HCT116 cells except compound 3. The flow cytometric analysis revealed that the two compounds 5a and 5b induced apoptosis to 46.5% and 54.8% respectively, relative to control 8.06%. In addition, PCR results indicated that the two compounds 5a and 5b induced the expression of p53 gene and decreased induction of BCL2 (anti-apoptotic gene), while the two compounds have no effect on the protein expression of Caspase-9. By monitoring the presence of Caspase-3 which was a mean to detect apoptotic death in breast carcinoma, the two compounds have stimulated the induction of apoptosis by increasing the production of Caspase-3 protein. Finally, it was concluded that the two compounds 5b and 5a have the most promising anti-cancer activity against human breast carcinoma (MCF7), and it is believed that the anticancer activities of these two compounds were due to being the most effective in the inhibition of a member of IAPs groups, leading to activation of p53 gene and the Caspase-3 dependent apoptosis.
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http://dx.doi.org/10.1016/j.bioorg.2017.05.012DOI Listing
August 2017

Molecular docking simulation and anticancer assessment on human breast carcinoma cell line using novel bis(1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile) and bis(1,4-dihydropyrazolo[4',3':5,6]pyrano[2,3-b]pyridine-6-carbonitrile) derivatives.

Bioorg Chem 2017 04 21;71:19-29. Epub 2017 Jan 21.

Chemistry Department, Faculty of Science, Cairo University, Giza, Egypt. Electronic address:

An efficient route for the synthesis of novel bis(1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile) derivatives is reported. The synthetic pathway involves one pot, synthesis of bis-aldehydes, malononitrile, and pyrazolone in the presence of pyridine. The anticancer activity of the synthesized products against MCF7, HEPG2, and A549 cell lines was assessed. Docking studies were performed and indicated the best binding mode compared to the standard ligand sorafenib.
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http://dx.doi.org/10.1016/j.bioorg.2017.01.009DOI Listing
April 2017

Anticancer Activities of New N-hetaryl-2-cyanoacetamide Derivatives Incorporating 4,5,6,7-Tetrahydrobenzo[b]thiophene Moiety.

Anticancer Agents Med Chem 2017 ;17(8):1084-1092

Department of Chemistry, Faculty of Science, Cairo University, 12613 Giza, A. R, Egypt.

Aims: Novel series of N-(4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl) cyanoacetamide derivatives are synthesized.

Method: The structure of these compounds was elucidated using different spectral tools. Compounds were evaluated for their cytotoxic activities against different types of human cancer cell lines including, breast (MCF-7, T47D, MDA MB231); liver (HEPG-2); colon (HCT116); prostate (PC3); and cervix (HELA) cells. In this study, we used compounds 11 and 12 that showed the highest cytotoxicity on PC3 and HEPG2 cells, to explore their effects on apoptosis, metastasis and angiogenesis of cancer cells.

Results: Results revealed that the growth inhibition produced by the two selected compounds was due to cytocidal and not due to cytostatic effect in both cell lines. This cytocidal effect was due to up-regulation of caspases-3, and- 9. In addition, the two compounds inhibited the expression of metalloproteinases-2 and 9 (MMP 2&9). Moreover, HIF-1alpha and VEGF expressions were inhibited by both compounds.

Conclusion: In conclusion, N-(4, 5, 6, 7-tetrahydrobenzo[b]thiophen-2-yl) cyanoacetamide derivatives showed different anticancer potential against different cancer cell lines. Compounds 11 and 12 showed the most active cytotoxicity against PC3 and HepG2 cells. Both compounds have apoptotic, anti- metastatic and anti-angiogenic effects.
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http://dx.doi.org/10.2174/1871520617666170110154110DOI Listing
September 2017

Cytotoxic and antimicrobial evaluations of novel apoptotic and anti-angiogenic spiro cyclic 2-oxindole derivatives of 2-amino-tetrahydroquinolin-5-one.

Arch Pharm (Weinheim) 2015 Feb;348(2):113-24

Department of Chemistry, Faculty of Science, Cairo University, Giza, Egypt.

A novel series of cyclic 2-oxindole derivatives incorporating 2-amino-tetrahydroquinolin-5-one were prepared. The structures of the prepared compounds were elucidated using different spectral tools. The regio-orientation of the reaction products was elucidated through NOE difference experiments and through using substituents on the ortho position to affect further cyclization. Antitumor and antimicrobial evaluations were performed on the prepared compounds. Most of these compounds exhibited high to moderate antimicrobial activity. With respect to the antitumor activity, the compounds showed more potent cytotoxic effect only toward the human breast cancer cell line MCF-7. Also, we found that derivatives containing an ester group (8c, 11b, 14b, and 15b) are more active than those containing a cyanide group (8a, 11a, 14a, and 15a). Moreover, compounds 15b and 8b are the most active derivatives in this group. These two compounds showed apoptotic inhibition of the proliferation of human breast adenocarcinoma MCF-7 cells through DNA fragmentation, induction of the tumor suppressor protein p53, induction of caspase-9, and finally the inhibition of angiogenesis by decreasing vascular endothelial growth factor expression and secretion.
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http://dx.doi.org/10.1002/ardp.201400304DOI Listing
February 2015

An easy synthesis of 5-functionally substituted ethyl 4-amino-1-aryl- pyrazolo-3-carboxylates: interesting precursors to sildenafil analogues.

Beilstein J Org Chem 2007 May 1;3:15. Epub 2007 May 1.

Department of Chemistry, Faculty of Science, Cairo University, Giza, A. R. Egypt.

3-Oxo-2-arylhydrazononitriles 1a-c react readily with chloroacetonitrile, ethyl chloroacetate, and with phenacyl chloride to give 4-aminopyrazoles 4a-e. The pyrazolo[4,3-d]pyrimidine derivatives 7 and 10 are synthesized via reaction of the aminopyrazole 4b with phenylisothiocyanate and DMFDMA/NH4OAc respectively.
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http://dx.doi.org/10.1186/1860-5397-3-15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1885264PMC
May 2007
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