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Synthesis, cytotoxicity and QSAR study of N-tosyl-1,2,3,4-tetrahydroisoquinoline derivatives

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Abstract

1-Substituted-N-tosyl-1,2,3,4-tetrahydroisoquinoline analogs (4a–4l) were synthesized using the modified Pictet–Spengler reaction and evaluated for cytotoxicity. All tetrahydroisoquinolines displayed cytotoxicity against MOLT-3 cell lines, except for p-methoxy analog 4d. Interestingly, the o-hydroxy derivative 4k was shown to be the most potent cytotoxic against HuCCA-1, A-549 and MOLT-3 cell lines. The lowest IC50 value of 1.23 μM was observed for MOLT-3 cells. Trimethoxy analog 4f exerted the most potent activity against HepG2 with an IC50 of 22.70 μM, which is lower than the reference drug, etoposide. QSAR studies showed that total symmetry index (Gu), 3D-MoRSE (Mor31v and Mor32u) and 3D Petitjean index (PJI3) were the most important descriptors accounting for the observed cytotoxicities. The most potent cytotoxic compound (4k) against MOLT-3 had the highest Gu value, correspondingly the inactive p-methoxy analog (4d) had the lowest Gu value. On the other hand, the highest molecular mass compound (4f) was shown to be the most potent cytotoxic against HepG2 cells. The studies disclose that tetrahydroisoquinolines 4f and 4k are potentially interesting lead pharmacophores that should be further explored. The QSAR models provided insights into the physicochemical properties of the investigated compounds.

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Acknowledgments

We gratefully acknowledge the research grant supported by Srinakharinwirot University (B.E. 2555). This project is supported by Office of the Higher Education Commission and Mahidol University under the National Research Universities Initiative. R.P. sincerely thanks the financial support from the Science and Technology Research Grant of the Thailand Toray Science Foundation.

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Authors and Affiliations

  1. Department of Chemistry, Faculty of Science, Srinakharinwirot University, Bangkok, 10110, Thailand

    Ratchanok Pingaew

  2. Center of Data Mining and Biomedical Informatics, Faculty of Medical Technology, Mahidol University, Bangkok, 10700, Thailand

    Apilak Worachartcheewan, Chanin Nantasenamat & Supaluk Prachayasittikul

  3. Department of Clinical Microbiology and Applied Technology, Faculty of Medical Technology, Mahidol University, Bangkok, 10700, Thailand

    Apilak Worachartcheewan, Chanin Nantasenamat & Virapong Prachayasittikul

  4. Chulabhorn Research Institute and Chulabhorn Graduate Institute, Bangkok, 10210, Thailand

    Somsak Ruchirawat

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  1. Ratchanok Pingaew
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Pingaew, R., Worachartcheewan, A., Nantasenamat, C. et al. Synthesis, cytotoxicity and QSAR study of N-tosyl-1,2,3,4-tetrahydroisoquinoline derivatives. Arch. Pharm. Res. 36, 1066–1077 (2013). https://doi.org/10.1007/s12272-013-0111-9

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