BIOMAT Database Logo BIOMAT Database Logo

New quinoline and isatin derivatives as apoptotic VEGFR-2 inhibitors: design, synthesis, anti-proliferative activity, docking, ADMET, toxicity, and MD simulation studies. 2022

Eslam B Elkaeed, and Mohammed S Taghour, and Hazem A Mahdy, and Wagdy M Eldehna, and Nehal M El-Deeb, and Ahmed M Kenawy, and Bshra A Alsfouk, and Mohammed A Dahab, and Ahmed M Metwaly, and Ibrahim H Eissa, and Mohamed A El-Zahabi
Department of Pharmaceutical Sciences, College of Pharmacy, AlMaarefa University, Riyadh, 13713, Saudi Arabia.

New quinoline and isatin derivatives having the main characteristics of VEGFR-2 inhibitors was synthesised. The antiproliferative effects of these compounds were estimated against A549, Caco-2, HepG2, and MDA-MB-231. Compounds 13 and 14 showed comparable activities with doxorubicin against the Caco-2 cells. These compounds strongly inhibited VEGFR-2 kinase activity. The cytotoxic activities were evaluated against Vero cells. Compound 7 showed the highest value of safety and selectivity. Cell migration assay displayed the ability of compound 7 to prevent healing and migration abilities in the cancer cells. Furthermore, compound 7 induced apoptosis in Caco-2 through the expressive down-regulation of the apoptotic genes, Bcl2, Bcl-xl, and Survivin, and the upregulation of the TGF gene. Molecular docking against VEGFR-2 emerged the interactions of the synthesised compounds in a similar way to sorafenib. Additionally, seven molecular dynamics simulations studies were applied and confirmed the stability of compound 13 in the active pocket of VEGFR-2 over 100 ns.

UI MeSH Term Description Entries
D007510 Isatin An indole-dione that is obtained by oxidation of indigo blue. It is a MONOAMINE OXIDASE INHIBITOR and high levels have been found in urine of PARKINSONISM patients. 2,3-Dioxoindoline,2,3 Dioxoindoline
D011804 Quinolines
D002522 Chlorocebus aethiops A species of CERCOPITHECUS containing three subspecies: C. tantalus, C. pygerythrus, and C. sabeus. They are found in the forests and savannah of Africa. The African green monkey is the natural host of SIMIAN IMMUNODEFICIENCY VIRUS and is used in AIDS research. African Green Monkey,Cercopithecus aethiops,Cercopithecus griseoviridis,Cercopithecus griseus,Cercopithecus pygerythrus,Cercopithecus sabeus,Cercopithecus tantalus,Chlorocebus cynosuros,Chlorocebus cynosurus,Chlorocebus pygerythrus,Green Monkey,Grivet Monkey,Lasiopyga weidholzi,Malbrouck,Malbrouck Monkey,Monkey, African Green,Monkey, Green,Monkey, Grivet,Monkey, Vervet,Savanah Monkey,Vervet Monkey,Savannah Monkey,African Green Monkey,Chlorocebus cynosuro,Green Monkey, African,Green Monkeys,Grivet Monkeys,Malbrouck Monkeys,Malbroucks,Monkey, Malbrouck,Monkey, Savanah,Monkey, Savannah,Savannah Monkeys,Vervet Monkeys
D004354 Drug Screening Assays, Antitumor Methods of investigating the effectiveness of anticancer cytotoxic drugs and biologic inhibitors. These include in vitro cell-kill models and cytostatic dye exclusion tests as well as in vivo measurement of tumor growth parameters in laboratory animals. Anticancer Drug Sensitivity Tests,Antitumor Drug Screens,Cancer Drug Tests,Drug Screening Tests, Tumor-Specific,Dye Exclusion Assays, Antitumor,Anti-Cancer Drug Screens,Antitumor Drug Screening Assays,Tumor-Specific Drug Screening Tests,Anti Cancer Drug Screens,Anti-Cancer Drug Screen,Antitumor Drug Screen,Cancer Drug Test,Drug Screen, Anti-Cancer,Drug Screen, Antitumor,Drug Screening Tests, Tumor Specific,Drug Screens, Anti-Cancer,Drug Screens, Antitumor,Drug Test, Cancer,Drug Tests, Cancer,Screen, Anti-Cancer Drug,Screen, Antitumor Drug,Screens, Anti-Cancer Drug,Screens, Antitumor Drug,Test, Cancer Drug,Tests, Cancer Drug,Tumor Specific Drug Screening Tests
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000970 Antineoplastic Agents Substances that inhibit or prevent the proliferation of NEOPLASMS. Anticancer Agent,Antineoplastic,Antineoplastic Agent,Antineoplastic Drug,Antitumor Agent,Antitumor Drug,Cancer Chemotherapy Agent,Cancer Chemotherapy Drug,Anticancer Agents,Antineoplastic Drugs,Antineoplastics,Antitumor Agents,Antitumor Drugs,Cancer Chemotherapy Agents,Cancer Chemotherapy Drugs,Chemotherapeutic Anticancer Agents,Chemotherapeutic Anticancer Drug,Agent, Anticancer,Agent, Antineoplastic,Agent, Antitumor,Agent, Cancer Chemotherapy,Agents, Anticancer,Agents, Antineoplastic,Agents, Antitumor,Agents, Cancer Chemotherapy,Agents, Chemotherapeutic Anticancer,Chemotherapy Agent, Cancer,Chemotherapy Agents, Cancer,Chemotherapy Drug, Cancer,Chemotherapy Drugs, Cancer,Drug, Antineoplastic,Drug, Antitumor,Drug, Cancer Chemotherapy,Drug, Chemotherapeutic Anticancer,Drugs, Antineoplastic,Drugs, Antitumor,Drugs, Cancer Chemotherapy
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D014709 Vero Cells A CELL LINE derived from the kidney of the African green (vervet) monkey, (CHLOROCEBUS AETHIOPS) used primarily in virus replication studies and plaque assays. Cell, Vero,Cells, Vero,Vero Cell
D015394 Molecular Structure The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds. Structure, Molecular,Molecular Structures,Structures, Molecular

Related Publications

Eslam B Elkaeed, and Mohammed S Taghour, and Hazem A Mahdy, and Wagdy M Eldehna, and Nehal M El-Deeb, and Ahmed M Kenawy, and Bshra A Alsfouk, and Mohammed A Dahab, and Ahmed M Metwaly, and Ibrahim H Eissa, and Mohamed A El-Zahabi
Discovery of New VEGFR-2 Inhibitors: Design, Synthesis, Anti-Proliferative Evaluation, Docking, and MD Simulation Studies.
September 2022, Molecules (Basel, Switzerland),
Eslam B Elkaeed, and Mohammed S Taghour, and Hazem A Mahdy, and Wagdy M Eldehna, and Nehal M El-Deeb, and Ahmed M Kenawy, and Bshra A Alsfouk, and Mohammed A Dahab, and Ahmed M Metwaly, and Ibrahim H Eissa, and Mohamed A El-Zahabi
Discovery of new nicotinamides as apoptotic VEGFR-2 inhibitors: virtual screening, synthesis, anti-proliferative, immunomodulatory, ADMET, toxicity, and molecular dynamic simulation studies.
December 2022, Journal of enzyme inhibition and medicinal chemistry,
Eslam B Elkaeed, and Mohammed S Taghour, and Hazem A Mahdy, and Wagdy M Eldehna, and Nehal M El-Deeb, and Ahmed M Kenawy, and Bshra A Alsfouk, and Mohammed A Dahab, and Ahmed M Metwaly, and Ibrahim H Eissa, and Mohamed A El-Zahabi
Discovery of New Quinazoline Derivatives as VEGFR-2 Inhibitors: Design, Synthesis, and Anti-proliferative Studies.
January 2023, Anti-cancer agents in medicinal chemistry,
Eslam B Elkaeed, and Mohammed S Taghour, and Hazem A Mahdy, and Wagdy M Eldehna, and Nehal M El-Deeb, and Ahmed M Kenawy, and Bshra A Alsfouk, and Mohammed A Dahab, and Ahmed M Metwaly, and Ibrahim H Eissa, and Mohamed A El-Zahabi
Design, synthesis, docking, ADMET studies, and anticancer evaluation of new 3-methylquinoxaline derivatives as VEGFR-2 inhibitors and apoptosis inducers.
December 2021, Journal of enzyme inhibition and medicinal chemistry,
Eslam B Elkaeed, and Mohammed S Taghour, and Hazem A Mahdy, and Wagdy M Eldehna, and Nehal M El-Deeb, and Ahmed M Kenawy, and Bshra A Alsfouk, and Mohammed A Dahab, and Ahmed M Metwaly, and Ibrahim H Eissa, and Mohamed A El-Zahabi
Design, Molecular Modeling, MD Simulations, Essential Dynamics, ADMET, DFT, Synthesis, Anti-proliferative, and Apoptotic Evaluations of a New Anti-VEGFR-2 Nicotinamide Analogue.
January 2023, Current pharmaceutical design,
Eslam B Elkaeed, and Mohammed S Taghour, and Hazem A Mahdy, and Wagdy M Eldehna, and Nehal M El-Deeb, and Ahmed M Kenawy, and Bshra A Alsfouk, and Mohammed A Dahab, and Ahmed M Metwaly, and Ibrahim H Eissa, and Mohamed A El-Zahabi
Design, semi-synthesis, anti-cancer assessment, docking, MD simulation, and DFT studies of novel theobromine-based derivatives as VEGFR-2 inhibitors and apoptosis inducers.
December 2023, Computational biology and chemistry,
Eslam B Elkaeed, and Mohammed S Taghour, and Hazem A Mahdy, and Wagdy M Eldehna, and Nehal M El-Deeb, and Ahmed M Kenawy, and Bshra A Alsfouk, and Mohammed A Dahab, and Ahmed M Metwaly, and Ibrahim H Eissa, and Mohamed A El-Zahabi
New quinoxaline-based VEGFR-2 inhibitors: design, synthesis, and antiproliferative evaluation with in silico docking, ADMET, toxicity, and DFT studies.
September 2021, RSC advances,
Eslam B Elkaeed, and Mohammed S Taghour, and Hazem A Mahdy, and Wagdy M Eldehna, and Nehal M El-Deeb, and Ahmed M Kenawy, and Bshra A Alsfouk, and Mohammed A Dahab, and Ahmed M Metwaly, and Ibrahim H Eissa, and Mohamed A El-Zahabi
Design, synthesis, docking, ADMET profile, and anticancer evaluations of novel thiazolidine-2,4-dione derivatives as VEGFR-2 inhibitors.
July 2021, Archiv der Pharmazie,
Eslam B Elkaeed, and Mohammed S Taghour, and Hazem A Mahdy, and Wagdy M Eldehna, and Nehal M El-Deeb, and Ahmed M Kenawy, and Bshra A Alsfouk, and Mohammed A Dahab, and Ahmed M Metwaly, and Ibrahim H Eissa, and Mohamed A El-Zahabi
Design, Synthesis, Molecular Docking, and Anticancer Activity of Phthalazine Derivatives as VEGFR-2 Inhibitors.
December 2017, Archiv der Pharmazie,
Eslam B Elkaeed, and Mohammed S Taghour, and Hazem A Mahdy, and Wagdy M Eldehna, and Nehal M El-Deeb, and Ahmed M Kenawy, and Bshra A Alsfouk, and Mohammed A Dahab, and Ahmed M Metwaly, and Ibrahim H Eissa, and Mohamed A El-Zahabi
Design, synthesis, molecular docking, and anticancer activity of benzoxazole derivatives as VEGFR-2 inhibitors.
October 2019, Archiv der Pharmazie,
Copied contents to your clipboard!