title: Synthesis, cytotoxicity, and QSAR study of new aza-cyclopenta[b]fluorene-1,9-dione derivatives.
abstract: Thirty novel derivatives of aza-cyclopenta[b]fluorene-1,9-dione were synthesized, and their cytotoxic activities were tested against HeLa, LS180, MCF-7, and Raji cancer cell lines by MTT assay. Two derivatives containing nitrofuryl moiety, including 10-(5-nitro-furan-2-yl)-2,3-dihydro-4-aza-cyclopenta[b]fluorene-1,9-dione (IC(50)  range: 5.7-13.0 μm) and 10-(5-Nitro-furan-2-yl)-2,3,4,10-tetrahydro-4-aza-cyclopenta[b]fluorene-1,9-dione (IC(50)  range: 3.6-20.2 μm), as well as 10-(2-Nitro-phenyl)-2,3,4,10-tetrahydro-4-aza-cyclopenta[b]fluorene-1,9-dione (IC(50)  range: 3.1-27.1 μm) with nitrophenyl moiety on C10 position, were the most effective compounds. Furthermore, the effect of physiochemical descriptors on the cytotoxicity was evaluated by quantitative structure-activity relationship analysis. The quantitative structure-activity relationship results showed that molecular dipole moment, molar refractivity, fragment-based parameters, and some topological indices were influential on the cytotoxic effect. Finally, the good correlation that was found among cytotoxic data obtained from different cell lines may be an implication of a common cytotoxic mechanism in these cell lines. These findings provide useful structural information for the rational design and synthesis of efficient chemotherapeutic agents for treatment for cancer.
authors.affiliation: Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. mirir@sums.ac.ir
authors.forename: Ramin
authors.initials: R
authors.lastname: Miri
authors.forename: Omidreza
authors.initials: O
authors.lastname: Firuzi
authors.forename: Payam
authors.initials: P
authors.lastname: Peymani
authors.forename: Meysam
authors.initials: M
authors.lastname: Zamani
authors.forename: Ahmad Reza
authors.initials: AR
authors.lastname: Mehdipour
authors.forename: Zahra
authors.initials: Z
authors.lastname: Heydari
authors.forename: Maryam Masteri
authors.initials: MM
authors.lastname: Farahani
authors.forename: Abbas
authors.initials: A
authors.lastname: Shafiee
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D001372:Aza Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003517:Cyclopentanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D004354:Drug Screening Assays, Antitumor; D005449:Fluorenes / Q000138:chemical synthesis* / Q000737:chemistry* / Q000633:toxicity; D006801:Humans; D021281:Quantitative Structure-Activity Relationship
chemical_list: C571390:10-(2-nitro-phenyl)-2,3,4,10-tetrahydro-4-aza-cyclopenta(b)fluorene-1,9-dione; C571391:10-(5-nitro-furan-2-yl)-2,3,4,10-tetrahydro-4-aza-cyclopenta(b)fluorene-1,9-dione; C571389:10-(5-nitro-furan-2-yl)-2,3-dihydro-4-aza-cyclopenta(b)fluorene-1,9-dione; D000970:Antineoplastic Agents; D001372:Aza Compounds; D003517:Cyclopentanes; D005449:Fluorenes; C041509:fluorene