Synthesis, Cytotoxicity, and QSAR Study of New Aza-cyclopenta[b]fluorene-1,9-dione Derivatives

Authors

  • Ramin Miri,

    Corresponding author
    1. Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
    2. Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
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  • Omidreza Firuzi,

    1. Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
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  • Payam Peymani,

    1. Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
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  • Meysam Zamani,

    1. Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
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  • Ahmad Reza Mehdipour,

    1. Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
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  • Zahra Heydari,

    1. Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
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  • Maryam Masteri Farahani,

    1. Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
    2. Azad University Shahr-e-Rey Branch, Tehran, Iran
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  • Abbas Shafiee

    1. Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
    2. Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 14174, Iran
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Corresponding author: Ramin Miri, mirir@sums.ac.ir

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 (IC50 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 (IC50 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 (IC50 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.

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