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Antitumor evaluation and 3D-QSAR studies of a new series of the spiropyrroloquinoline isoindolinone/aza-isoindolinone derivatives by comparative molecular field analysis (CoMFA)

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Abstract

In current study, antitumor activity of two series of the newly synthesized spiropyrroloquinoline isoindolinone and spiropyrroloquinoline aza-isoindolinone scaffolds was evaluated against three human breast normal and cancer cell lines (MCF-10A, MCF-7 and SK-BR-3) and compared with cytotoxicity values of doxorubicin and colchicine as the standard drugs. It was found that several compounds were endowed with cytotoxicity in the low micromolar range. Among these two series, compounds 6i, 6j, 6k and 7l, 7m, 7n, 7o containing 3-ethyl-1H-indole moiety were found to be highly effective against both cancer cell lines ranging from \(0.080 \pm 0.001\) to \(11.91 \pm 1.39\,\upmu \hbox {M}\) in comparison with the corresponding analogs. Compared with human cancer cells, the most potent compounds did not show high cytotoxicity against human breast normal MCF-10A cells. Generally, most of the evaluated compounds 6a–l and 7a–o series showed more antitumor activity against SK-BR-3 than MCF-7 cells. Moreover, comparative molecular field analysis (CoMFA) as a popular tools of three-dimensional quantitative structure–activity relationship (3D-QSAR) studies was carried out on 27 spiropyrroloquinolineisoindolinone and spiropyrroloquinolineaza-isoindolinone derivatives with antitumor activity against on SK-BR-3 cells. The obtained CoMFA models showed statistically excellent performance, which also possessed good predictive ability for an external test set. The results confirm the important effect of molecular steric and electrostatic interactions of these compounds on in vitro cytotoxicity against SK-BR-3.

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Acknowledgements

Financial support by Radiation Application Research School of the Nuclear Science & Technology Research Institute is gratefully acknowledged.

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Authors and Affiliations

  1. Radiation Application Research School, Nuclear Science and Technology Research Institute, AEOI, P.O. Box 11365-3486, Tehran, Iran

    Masoud Sadeghzadeh, Maryam Salahinejad & Maryam Keshavarz Baghery

  2. School of Chemistry, College of Science, University of Tehran, P.O. Box 14155 6455, Tehran, Iran

    Nahid Zarezadeh & Mehdi Ghandi

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  1. Masoud Sadeghzadeh
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Correspondence to Masoud Sadeghzadeh.

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Sadeghzadeh, M., Salahinejad, M., Zarezadeh, N. et al. Antitumor evaluation and 3D-QSAR studies of a new series of the spiropyrroloquinoline isoindolinone/aza-isoindolinone derivatives by comparative molecular field analysis (CoMFA). Mol Divers 21, 821–830 (2017). https://doi.org/10.1007/s11030-017-9778-z

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