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The anti-invasive role of novel synthesized pyridazine hydrazide appended phenoxy acetic acid against neoplastic development targeting matrix metallo proteases.

Abstract

Neoplastic metastasis is a major process where tumor cells migrate from the primary tumor and colonize at other parts of our body to form secondary tumor. Cancer incidences are rising and novel anti-neoplastic compounds with new mechanism of actions are essential for preventing cancer related deaths. In the current examination, a novel series of pyridazine analogues 6a-l was synthesized and evaluated against metastatic neoplastic cells. Experimental data postulated compound 6j has potential cytotoxic efficacy with prolonged activity against various cancer cells, including A549, HepG2, A498, CaSki and SiHa cells. Moreover, compound 6j arrests the A549 migration and invasions markedly by counteracting matrix metalloproteinase (MMP)-2 and MMP-9 expressions. Also, compound 6j proved its potentiality against Dalton's solid lymphoma progression in-vivo by abridging MVD and MMP expressions. Compound 6j interacts with MMP-2 and MMP-9 by H- bond in-silico, thereby down regulates the MMPs action in tumourigenesis. Altogether, we concluded that compound 6j down regulates MMP-2 and MMP-9 and thereby impairs metastatic cancer cell migration and invasions which can be translated into a potent anti-neoplastic agent.

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  • Authors+Show Affiliations

    ,

    Department of Chemistry, Yuvaraja's College, University of Mysore, Mysore, 570005 Karnataka, India; Department of Biochemistry, Faculty of Applied Science College, University of Hajjah, Yemen.

    ,

    Molecular Onco-medicine Laboratory, Postgraduate Department of Studies and Research in Biotechnology, Sahyadri Science College (A), Kuvempu University, Shivamogga, 577203, Karnataka, India.

    ,

    Department of Chemistry, Yuvaraja's College, University of Mysore, Mysore, 570005 Karnataka, India.

    ,

    Molecular Onco-medicine Laboratory, Postgraduate Department of Studies and Research in Biotechnology, Sahyadri Science College (A), Kuvempu University, Shivamogga, 577203, Karnataka, India.

    ,

    Molecular Onco-medicine Laboratory, Postgraduate Department of Studies and Research in Biotechnology, Sahyadri Science College (A), Kuvempu University, Shivamogga, 577203, Karnataka, India.

    Department of Chemistry, Yuvaraja's College, University of Mysore, Mysore, 570005 Karnataka, India. Electronic address: shaukathara@yahoo.co.in.

    Source

    MeSH

    Animals
    Carcinogenesis
    Cell Line, Tumor
    Cell Movement
    Computer Simulation
    Down-Regulation
    Humans
    Hydrazines
    Inhibitory Concentration 50
    Male
    Matrix Metalloproteinases
    Mice
    Microvessels
    Models, Molecular
    NIH 3T3 Cells
    Neoplasm Invasiveness
    Phenoxyacetates
    Pyridazines
    Structure-Activity Relationship

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    28858736

    Citation

    Eissa Mohammed, Yasser Hussein, et al. "The Anti-invasive Role of Novel Synthesized Pyridazine Hydrazide Appended Phenoxy Acetic Acid Against Neoplastic Development Targeting Matrix Metallo Proteases." Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, vol. 95, 2017, pp. 375-386.
    Eissa Mohammed YH, Thirusangu P, Zabiulla , et al. The anti-invasive role of novel synthesized pyridazine hydrazide appended phenoxy acetic acid against neoplastic development targeting matrix metallo proteases. Biomed Pharmacother. 2017;95:375-386.
    Eissa Mohammed, Y. H., Thirusangu, P., Zabiulla, ., V, V., B T, P., & Khanum, S. A. (2017). The anti-invasive role of novel synthesized pyridazine hydrazide appended phenoxy acetic acid against neoplastic development targeting matrix metallo proteases. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, 95, pp. 375-386. doi:10.1016/j.biopha.2017.08.105.
    Eissa Mohammed YH, et al. The Anti-invasive Role of Novel Synthesized Pyridazine Hydrazide Appended Phenoxy Acetic Acid Against Neoplastic Development Targeting Matrix Metallo Proteases. Biomed Pharmacother. 2017;95:375-386. PubMed PMID: 28858736.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - The anti-invasive role of novel synthesized pyridazine hydrazide appended phenoxy acetic acid against neoplastic development targeting matrix metallo proteases. AU - Eissa Mohammed,Yasser Hussein, AU - Thirusangu,Prabhu, AU - Zabiulla,, AU - V,Vigneshwaran, AU - B T,Prabhakar, AU - Khanum,Shaukath Ara, Y1 - 2017/09/12/ PY - 2017/03/03/received PY - 2017/08/16/revised PY - 2017/08/23/accepted PY - 2017/9/1/pubmed PY - 2018/6/21/medline PY - 2017/9/1/entrez KW - Cancer KW - Dalton’s lymphoma KW - MMPs KW - Metastasis KW - Pyridazine SP - 375 EP - 386 JF - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JO - Biomed. Pharmacother. VL - 95 N2 - Neoplastic metastasis is a major process where tumor cells migrate from the primary tumor and colonize at other parts of our body to form secondary tumor. Cancer incidences are rising and novel anti-neoplastic compounds with new mechanism of actions are essential for preventing cancer related deaths. In the current examination, a novel series of pyridazine analogues 6a-l was synthesized and evaluated against metastatic neoplastic cells. Experimental data postulated compound 6j has potential cytotoxic efficacy with prolonged activity against various cancer cells, including A549, HepG2, A498, CaSki and SiHa cells. Moreover, compound 6j arrests the A549 migration and invasions markedly by counteracting matrix metalloproteinase (MMP)-2 and MMP-9 expressions. Also, compound 6j proved its potentiality against Dalton's solid lymphoma progression in-vivo by abridging MVD and MMP expressions. Compound 6j interacts with MMP-2 and MMP-9 by H- bond in-silico, thereby down regulates the MMPs action in tumourigenesis. Altogether, we concluded that compound 6j down regulates MMP-2 and MMP-9 and thereby impairs metastatic cancer cell migration and invasions which can be translated into a potent anti-neoplastic agent. SN - 1950-6007 UR - https://www.unboundmedicine.com/medline/citation/28858736/The_anti-invasive_role_of_novel_synthesized_pyridazine_hydrazide_appended_phenoxy_acetic_acid_against_neoplastic_development_targeting_matrix_metallo_proteases L2 - https://linkinghub.elsevier.com/retrieve/pii/S0753-3322(17)30989-7 DB - PRIME DP - Unbound Medicine ER -