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Exploring the molecular basis for selective cytotoxicity of lamellarins against human hormone-dependent T47D and hormone-independent MDA-MB-231 breast cancer cells

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Abstract

The common structural requirements for cytotoxicity of lamellarins against two human breast cancer cell lines were determined using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) techniques. Twenty lamellarins were selected to serve as the training set, whereas another group of six compounds were used as the test set. The best CoMFA and CoMSIA models for both cell lines yielded satisfactory predictive ability with r 2cv values in the range of 0.659–0.728. Additionally, the contour maps obtained from both the CoMFA and CoMSIA models agreed well with the experimental results and may be used in the design of more potent cytotoxic compounds for human breast cancers. Both analyses not only suggested structural requirements of various substituents around the lamellarin skeleton for their cytotoxic activity against both human breast cancer cell lines but also revealed the molecular basis for the differences between the saturated and unsaturated D-rings of the lamellarins.

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Acknowledgments

This work would not have been possible without generous support from the Chulabhorn Research Institute (CRI), the Chulabhorn Graduate Institute (CGI), Phetchaburi Rajabhat University (PBRU), the Kasetsart University (KU) Graduate School, and the Commission on Higher Education (CHE). The Thailand Research Fund (TRF) is gratefully acknowledged for research grants (RTA5080005 to S.H., BRG5180013 to P.P., RMU4980048 to N.T., and DBG5180015 to M.C.). Moreover, the authors would like to thank the National Center of Excellence in Petroleum, Petrochemicals, and Advanced Materials, KU Research and Development Institute (KURDI), Laboratory for Computational and Applied Chemistry (LCAC) and the computing centre of KU, the Center of Nanotechnology KU, NANOTEC Center of Excellence at KU, and the Large Scale Research Laboratory of the National Electronics and Computer Technology (NECTEC) for computing and research facilities.

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Authors and Affiliations

  1. Department of Chemistry, Faculty of Science, Kasetsart University (KU), Chatuchak, Bangkok, 10900, Thailand

    Poonsiri Thipnate, Patchreenart Saparpakorn & Supa Hannongbua

  2. Center of Nanotechnology, Kasetsart University (KU), Chatuchak, Bangkok, 10900, Thailand

    Poonsiri Thipnate, Patchreenart Saparpakorn & Supa Hannongbua

  3. Chulabhorn Research Institute and Chulabhorn Graduate Institute, Vibhavadee-Rangsit Highway, Laksi, Bangkok, 10210, Thailand

    Montakarn Chittchang, Nopporn Thasana & Poonsakdi Ploypradith

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  1. Poonsiri Thipnate
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  2. Montakarn Chittchang
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  3. Nopporn Thasana
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  4. Patchreenart Saparpakorn
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  5. Poonsakdi Ploypradith
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  6. Supa Hannongbua
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Correspondence to Supa Hannongbua.

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Thipnate, P., Chittchang, M., Thasana, N. et al. Exploring the molecular basis for selective cytotoxicity of lamellarins against human hormone-dependent T47D and hormone-independent MDA-MB-231 breast cancer cells. Monatsh Chem 142, 97–109 (2011). https://doi.org/10.1007/s00706-010-0409-y

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  • DOI: https://doi.org/10.1007/s00706-010-0409-y

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