title: Synthesis and in vitro evaluation of 3-(4-nitrophenyl)coumarin derivatives in tumor cell lines.
abstract: Coumarins are naturally-occurring compounds that have attracted considerable interest due to their numerous biological activities depending on their pattern of substitution on the coumarin molecule. In this present investigation, we synthesized 3-(4-nitrophenyl)coumarin derivatives (9a-e) and evaluated their in vitro cytotoxic effect on human lung (A549), breast (MDA-MB-231) and prostate (PC3) cancer cell lines for 48 h using crystal violet dye binding assay. Cytotoxic effects of the most active compound on normal human lung (MRC-9) and breast (MCF-10A) cell lines, cell cycle analysis using flow cytometry and mitochondrial membrane potential (MMP) using Tetramethyl Rhodamine Methyl Ester (TMRM; rhodamine-123) fluorescent dye were also examined. Among the compounds that were evaluated, 9c showed cytotoxic effect (active), caused significant cells arrest (p<0.05) in G0/G1 and S phases of cell cycle and loss of MMP in A459, MDA-MB-231 and PC3 cell lines. Additionally, the cytotoxic effect of 9c was compared to reference drugs (Coumarin and Docetaxel) for comparative study. These results further demonstrate that acetoxy group at C-7 and C-8 positions of 9c are responsible for the observed cytotoxic effect in these cancer cell lines.
authors.affiliation: Departments of Chemistry, Florida A&M University, Tallahassee, FL 32307, USA. Electronic address: musiliyu.musa@famu.edu.
authors.forename: Musiliyu A
authors.initials: MA
authors.lastname: Musa
authors.affiliation: Department of Biological Science, Florida A&M University, Tallahassee, FL 32307, USA.
authors.forename: Lekan M
authors.initials: LM
authors.lastname: Latinwo
authors.affiliation: Departments of Chemistry, Florida A&M University, Tallahassee, FL 32307, USA.
authors.forename: Clifford
authors.initials: C
authors.lastname: Virgile
authors.affiliation: Department of Biological Science, Florida A&M University, Tallahassee, FL 32307, USA.
authors.forename: Veera L D
authors.initials: VL
authors.lastname: Badisa
authors.affiliation: Department of Biological Science, Florida A&M University, Tallahassee, FL 32307, USA.
authors.forename: Akintunde J
authors.initials: AJ
authors.lastname: Gbadebo
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D066241:Carbon-13 Magnetic Resonance Spectroscopy; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D003374:Coumarins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D066298:In Vitro Techniques; D066244:Proton Magnetic Resonance Spectroscopy; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: C000601823:7,8-diacetoxy-3-(4-nitrophenyl)coumarin; D000970:Antineoplastic Agents; D003374:Coumarins
keywords: 3-Arylcoumarin; Anticancer; Cell cycle; Cytotoxicity; Mitochondrial membrane potential