title: Nanofibrous matrixes with biologically active hydroxybenzophenazine pyrazolone compound for cancer theranostics.
abstract: The nanomaterial with the novel biologically active compounds has been actively investigated for application in cancer research. Substantial use of nanofibrous scaffold for cancer research with potentially bioactive compounds through electrospinning has not been fully explored. Here, we describe the series of fabrication of nanofibrous scaffold loaded with novel potential biologically active hydroxybenzo[a]phenazine pyrazol-5(4H)-one derivatives were designed, synthesized by a simple one-pot, two step four component condensation based on Michael type addition reaction of lawsone, benzene-1,2-diamine, aromatic aldehydes and 3-methyl-1-phenyl-1H-pyrazol-5(4H)-one as the substrates. The heterogeneous solid state catalyst (Fe (III) Y-Zeolite) could effectively catalyze the reaction to obtain the product with high yield and short reaction time. The synthesized compounds (5a-5p) were analyzed by NMR, FTIR and HRMS analysis. Compound 5c was confirmed by single crystal XRD studies. All the compounds were biologically evaluated for their potential inhibitory effect on anticancer (MCF-7, Hep-2) and microbial (MRSA, MTCC 201 and FRCA) activities. Among the compounds 5i exhibited the highest levels of inhibitory activity against both MCF-7, Hep-2 cell lines. Furthermore, the compound 5i (BPP) was evaluated for DNA fragmentation, flow cytometry studies and cytotoxicity against MCF-7, Hep-2 and NIH 3T3 fibroblast cell lines. In addition, molecular docking (PDB ID: 1T46) studies were performed to predict the binding affinity of ligand with receptor. Moreover, the synthesized BPP compound was loaded in to the PHB-PCL nanofibrous scaffold to check the cytotoxicity against the MCF-7, Hep-2 and NIH 3T3 fibroblast cell lines. The in vitro apoptotic potential of the PHB-PCL-BPP nanofibrous scaffold was assessed against MCF-7, Hep-2 cancerous cells and fibroblast cells at 12, 24 and 48h respectively. The nanofibrous scaffold with BPP can induce apoptosis and also suppress the proliferation of cancerous cells. We anticipate that our results can provide better potential research in nanomaterial based cancer research.
authors.affiliation: Organic Chemistry Division, CSIR-Central Leather Research Institute, Adyar, Chennai 600020, Tamilnadu, India.
authors.forename: Subramani
authors.initials: S
authors.lastname: Kandhasamy
authors.affiliation: Bioproducts Lab, CSIR-Central Leather Research Institute, Chennai 600020, Tamilnadu, India.
authors.forename: Giriprasath
authors.initials: G
authors.lastname: Ramanathan
authors.affiliation: Department of Clinical and Experimental Medicine (IKE), Division of Neuro and Inflammation Sciences (NIV), Linkoping University, Sweden.
authors.forename: Thangavelu
authors.initials: T
authors.lastname: Muthukumar
authors.affiliation: Bioproducts Lab, CSIR-Central Leather Research Institute, Chennai 600020, Tamilnadu, India.
authors.forename: SitaLakshmi
authors.initials: S
authors.lastname: Thyagarajan
authors.affiliation: Organic Chemistry Division, CSIR-Central Leather Research Institute, Adyar, Chennai 600020, Tamilnadu, India.
authors.forename: Narayanan
authors.initials: N
authors.lastname: Umamaheshwari
authors.affiliation: Department of Plant Biotechnology, TNAU, Coimbatore, Tamilnadu, India.
authors.forename: V P
authors.initials: VP
authors.lastname: Santhanakrishnan
authors.affiliation: Bioproducts Lab, CSIR-Central Leather Research Institute, Chennai 600020, Tamilnadu, India. Electronic address: suma67@gmail.com.
authors.forename: Uma Tiruchirapalli
authors.initials: UT
authors.lastname: Sivagnanam
authors.affiliation: Organic Chemistry Division, CSIR-Central Leather Research Institute, Adyar, Chennai 600020, Tamilnadu, India. Electronic address: ptperumal@gmail.com.
authors.forename: Paramasivan Thirumalai
authors.initials: PT
authors.lastname: Perumal
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000737:chemistry / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D001665:Binding Sites; D002176:Candida albicans / Q000187:drug effects; D002384:Catalysis; D045744:Cell Line, Tumor; D053938:DNA Fragmentation / Q000187:drug effects; D065546:Drug Liberation; D005290:Ferric Compounds / Q000737:chemistry; D006801:Humans; D061986:MCF-7 Cells; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D051379:Mice; D008855:Microscopy, Electron, Scanning; D062105:Molecular Docking Simulation; D041681:NIH 3T3 Cells; D057139:Nanofibers / Q000737:chemistry*; D010619:Phenazines / Q000737:chemistry*; D000091402:Prohibitins; D017434:Protein Structure, Tertiary; D019009:Proto-Oncogene Proteins c-kit / Q000737:chemistry / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D047069:Pyrazolones / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D017550:Spectroscopy, Fourier Transform Infrared; D014961:X-Ray Diffraction
chemical_list: D000890:Anti-Infective Agents; D000970:Antineoplastic Agents; D005290:Ferric Compounds; C000717328:PHB protein, human; D010619:Phenazines; D000091402:Prohibitins; D047069:Pyrazolones; C000598831:phenazine; C038362:pyrazolone; D019009:Proto-Oncogene Proteins c-kit
keywords: Electrospinning; Hep-2; MCF-7; Nanofibrous scaffold; Nanomaterial; Tissue engineering