An article Battle tactics against MMP-9; discovery of novel non-hydroxamate MMP-9 inhibitors endowed with PI3K/AKT signaling attenuation and caspase 3/7 activation via Ugi bis-amide synthesis WOS:000509616800023 published article about MATRIX-METALLOPROTEINASE INHIBITORS; CANCER-CELL INVASION; BREAST-CANCER; MATRIX-METALLOPROTEINASE-9 ACTIVITY; CRYSTAL-STRUCTURES; TUMOR-GROWTH; DESIGN; ROLES; MULTICOMPONENT; OVEREXPRESSION in [Ayoup, Mohammed Salah; Fouad, Manar Ahmed; Abdel-Hamid, Hamida; Ramadan, El Sayed] Alexandria Univ, Fac Sci, Chem Dept, Alexandria 21321, Egypt; [Abu-Serie, Marwa M.] City Sci Res & Technol Applicat SRTA City, Genet Engn & Biotechnol Res Inst, Med Biotechnol Dept, Alexandria, Egypt; [Noby, Ahmed] Pharos Univ Alexandria, Fac Pharm, Dept Microbiol & Immunol, Alexandria 21311, Egypt; [Teleb, Mohamed] Alexandria Univ, Fac Pharm, Dept Pharmaceut Chem, Alexandria 21521, Egypt in 2020.0, Cited 84.0. The Name is 4-Nitrobenzoic acid. Through research, I have a further understanding and discovery of 62-23-7. Formula: C7H5NO4
Matrix metalloproteinases (MMPs) are major modulators of the tumor microenvironment. They participate in extracellular matrix turnover, tumor growth, angiogenesis and metastasis. Accordingly, MMPs inhibition seems to be ideal solution to control cancer. Many MMPs inhibitors have been introduced ranging from hydroxamate-based peptidomimetics to the next generation non-hydroxamate inhibitors. Among MMPs, MMP-9 is attractive druggable anticancer target. Studies showed that inhibiting AKT, the central signaling node of MMP-9 upregulation, provides additional MMP-9 blockade. Furthermore, caspase-dependent AKT cleavage leads to cell death. Herein, Ugi MCR was utilized as a rapid combinatorial approach to generate various decorated bis-amide scaffolds as dual MMP-9/AKT inhibitors endowed with caspase 3/7 activation potential. The target adducts were designed to mimic the thematic structural features of non-hydroxamate MMP inhibitors. p-Nitrophenyl isonitrile 1 was utilized as structure entry to Ugi products with some structural similarities to amide-based caspase 3/7 activators. Besides, various acids, amines and aldehydes were employed as Ugi educts to enrich the SAR data. All adducts were screened for cytotoxicity against normal fibroblasts and three cancer cell lines; MCF-7, NFS-60 and HepG-2 utilizing MTT assay. 8,11 and 28 were more active and safer than doxorubicin with single-digit nM IC50 and promising selectivity. Mechanistically, they exhibited dual MMP-9/AKT inhibition at single-digit nM IC50 with excellent selectivity over MMP-1,-2 and -13, and induced >51% caspase 3/7 activation. Consequently, they induced >49% apoptosis as detected by flow cytometric analysis, and inhibited cell migration (metastasis) up to 97% in cancer cells. Docking simulations were nearly consistent with enzymatic evaluation, also declared possible binding modes and essential structure features of active compounds. In silico physicochemical properties, ligand efficiency and drug-likeness metrics were reasonable for all adducts. Interestingly, 8 and 28 can be considered as drug-like candidates. (C) 2019 Elsevier Masson SAS. All rights reserved.
Formula: C7H5NO4. About 4-Nitrobenzoic acid, If you have any questions, you can contact Ayoup, MS; Fouad, MA; Abdel-Hamid, H; Ramadan, E; Abu-Serie, MM; Noby, A; Teleb, M or concate me.
Reference:
Phthalazine – Wikipedia,
,Phthalazine | C8H6N2 – PubChem