BIOMAT Database Logo BIOMAT Database Logo

Design, synthesis, evaluation of new 3-acetylisoxazolines and their hybrid analogous as anticancer agents: In vitro and in silico analysis. 2022

Mourad Fawzi, and Ali Oubella, and Abdoullah Bimoussa, and Fatima Zahra Bamou, and Zein Alabdeen Khdar, and Aziz Auhmani, and Abdelkhalek Riahi, and Anthony Robert, and Hamid Morjani, and My Youssef Ait Itto
Laboratory of Organic Synthesis and Physico-Molecular Chemistry, Department of Chemistry, Faculty of Sciences Semlalia, Université Cadi Ayyad, BP PO Box 2390, Marrakech 40001, Morocco.

3-Acetylisoxazolines were synthesized by the reaction of natural (R)-limonene and (R)-carvone with acetone in the presence of iron (III) nitrate. The reaction showed to be highly peri- and regioselective. Next, using a 1,3-dipolar cycloaddition reaction, the mono-3-acylisoxazolines derived from these monoterpenes were evaluated for their reactivity with nitrilimines. Only the enone of carvone-isoxazoline was regioselectively reactive, providing a new fused isoxazoline-carvone-pyrazolines. The structure of all the newly synthesized mono-cycloadducts (3 & 5) and bis-cycloadducts (4 & 7a-c) were fully identified based on their HRMS and NMR spectral data. They have also been screened for their cytotoxic activity against four human cancer cell lines: fibrosarcoma (HT-1080), lung carcinoma (A-549), and breast (MCF-7 and MDA-MB-231) cell lines. The obtained results showed that compound 4 was a potent cytotoxic agent against all selected cells. The possible mechanism of apoptosis induction by compound 4 was investigated using Annexin-V binding assay, caspase-3/7 activity and analysis cell cycle progression. The compound 4 induced the early apoptosis of both MCF-7 and MDA-MB-231 through caspase-3/7 activation, and the compound 4 have elicited S and G2/M phase arrest in MCF-7and MDA-MB-231 cancer cells, respectively. For further target investigations, a molecular docking study was employed and it showed that compound 4 has an inhibitory activity against Pim-1 protein kinase. Molecular dynamics study showed that compound 4/Pim-1 complex was stable during the simulation run at different time intervals. In-Silico ADMET predicted that compound 4 has good pharmacokinetic properties with high estimated oral bioavailability.

UI MeSH Term Description Entries
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
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
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
D017209 Apoptosis A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, i.e., DNA FRAGMENTATION. It is genetically programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. Apoptosis, Extrinsic Pathway,Apoptosis, Intrinsic Pathway,Caspase-Dependent Apoptosis,Classic Apoptosis,Classical Apoptosis,Programmed Cell Death,Programmed Cell Death, Type I,Apoptoses, Extrinsic Pathway,Apoptoses, Intrinsic Pathway,Apoptosis, Caspase-Dependent,Apoptosis, Classic,Apoptosis, Classical,Caspase Dependent Apoptosis,Cell Death, Programmed,Classic Apoptoses,Extrinsic Pathway Apoptoses,Extrinsic Pathway Apoptosis,Intrinsic Pathway Apoptoses,Intrinsic Pathway Apoptosis
D045744 Cell Line, Tumor A cell line derived from cultured tumor cells. Tumor Cell Line,Cell Lines, Tumor,Line, Tumor Cell,Lines, Tumor Cell,Tumor Cell Lines
D049109 Cell Proliferation All of the processes involved in increasing CELL NUMBER including CELL DIVISION. Cell Growth in Number,Cellular Proliferation,Cell Multiplication,Cell Number Growth,Growth, Cell Number,Multiplication, Cell,Number Growth, Cell,Proliferation, Cell,Proliferation, Cellular
D051573 Proto-Oncogene Proteins c-pim-1 Serine-threonine protein kinases that relay signals from CYTOKINE RECEPTORS and are involved in control of CELL GROWTH PROCESSES; CELL DIFFERENTIATION; and APOPTOSIS. c-pim-1 Protein,pim-1 Proto-Oncogene Protein,Pim-1 Kinase,Proto-Oncogene Protein c-pim-1,Proto-Oncogene Protein pim-1,Kinase, Pim-1,Pim 1 Kinase,Proto Oncogene Protein c pim 1,Proto Oncogene Protein pim 1,Proto Oncogene Proteins c pim 1,c pim 1 Protein,c-pim-1, Proto-Oncogene Protein,c-pim-1, Proto-Oncogene Proteins,pim 1 Proto Oncogene Protein,pim-1, Proto-Oncogene Protein
D053148 Caspase 3 A short pro-domain caspase that plays an effector role in APOPTOSIS. It is activated by INITIATOR CASPASES such as CASPASE 9. Isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA. CASP3,Apopain,Caspase-3,Pro-Caspase-3,Procaspase-3,Pro Caspase 3,Procaspase 3

Related Publications

Mourad Fawzi, and Ali Oubella, and Abdoullah Bimoussa, and Fatima Zahra Bamou, and Zein Alabdeen Khdar, and Aziz Auhmani, and Abdelkhalek Riahi, and Anthony Robert, and Hamid Morjani, and My Youssef Ait Itto
Synthesis and evaluation of N-(4-(substituted)-3-(trifluoromethyl) phenyl) isobutyramides and their N-ethyl analogous as anticancer, anti-angiogenic & antioxidant agents: In vitro and in silico analysis.
June 2021, Computational biology and chemistry,
Mourad Fawzi, and Ali Oubella, and Abdoullah Bimoussa, and Fatima Zahra Bamou, and Zein Alabdeen Khdar, and Aziz Auhmani, and Abdelkhalek Riahi, and Anthony Robert, and Hamid Morjani, and My Youssef Ait Itto
1,2,3-Triazole-nimesulide hybrid: Their design, synthesis and evaluation as potential anticancer agents.
February 2017, Bioorganic & medicinal chemistry letters,
Mourad Fawzi, and Ali Oubella, and Abdoullah Bimoussa, and Fatima Zahra Bamou, and Zein Alabdeen Khdar, and Aziz Auhmani, and Abdelkhalek Riahi, and Anthony Robert, and Hamid Morjani, and My Youssef Ait Itto
New 1,3,4‒oxadiazole Quinazolines as Potential Anticancer Agents: Design, Synthesis, Biological Evaluation, and In silico Studies.
April 2024, Current drug discovery technologies,
Mourad Fawzi, and Ali Oubella, and Abdoullah Bimoussa, and Fatima Zahra Bamou, and Zein Alabdeen Khdar, and Aziz Auhmani, and Abdelkhalek Riahi, and Anthony Robert, and Hamid Morjani, and My Youssef Ait Itto
Design, synthesis and biological evaluation of 3-substituted-2-oxindole hybrid derivatives as novel anticancer agents.
July 2017, European journal of medicinal chemistry,
Mourad Fawzi, and Ali Oubella, and Abdoullah Bimoussa, and Fatima Zahra Bamou, and Zein Alabdeen Khdar, and Aziz Auhmani, and Abdelkhalek Riahi, and Anthony Robert, and Hamid Morjani, and My Youssef Ait Itto
Design, synthesis, in silico, and in vitro evaluation of 3-phenylpyrazole acetamide derivatives as antimycobacterial agents.
May 2021, Archiv der Pharmazie,
Mourad Fawzi, and Ali Oubella, and Abdoullah Bimoussa, and Fatima Zahra Bamou, and Zein Alabdeen Khdar, and Aziz Auhmani, and Abdelkhalek Riahi, and Anthony Robert, and Hamid Morjani, and My Youssef Ait Itto
Design, synthesis, anticancer evaluation, and in silico ADMET analysis of novel thalidomide analogs as promising immunomodulatory agents.
April 2023, RSC advances,
Mourad Fawzi, and Ali Oubella, and Abdoullah Bimoussa, and Fatima Zahra Bamou, and Zein Alabdeen Khdar, and Aziz Auhmani, and Abdelkhalek Riahi, and Anthony Robert, and Hamid Morjani, and My Youssef Ait Itto
New nicotinamide derivatives as potential anticancer agents targeting VEGFR-2: design, synthesis, in vitro, and in silico studies.
December 2023, Journal of biomolecular structure & dynamics,
Mourad Fawzi, and Ali Oubella, and Abdoullah Bimoussa, and Fatima Zahra Bamou, and Zein Alabdeen Khdar, and Aziz Auhmani, and Abdelkhalek Riahi, and Anthony Robert, and Hamid Morjani, and My Youssef Ait Itto
Design, synthesis and biological evaluation of arylcinnamide hybrid derivatives as novel anticancer agents.
June 2014, European journal of medicinal chemistry,
Mourad Fawzi, and Ali Oubella, and Abdoullah Bimoussa, and Fatima Zahra Bamou, and Zein Alabdeen Khdar, and Aziz Auhmani, and Abdelkhalek Riahi, and Anthony Robert, and Hamid Morjani, and My Youssef Ait Itto
1,5-Benzothiazepine Derivatives: Green Synthesis, In Silico and In Vitro Evaluation as Anticancer Agents.
June 2022, Molecules (Basel, Switzerland),
Mourad Fawzi, and Ali Oubella, and Abdoullah Bimoussa, and Fatima Zahra Bamou, and Zein Alabdeen Khdar, and Aziz Auhmani, and Abdelkhalek Riahi, and Anthony Robert, and Hamid Morjani, and My Youssef Ait Itto
Hybrid Analogues of Hydrazone and Phthalimide: Design, Synthesis, In vivo, In vitro, and In silico Evaluation as Analgesic Agents.
January 2024, Current computer-aided drug design,
Copied contents to your clipboard!