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Synthesis of novel 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole derivatives as antiproliferative agents: A structure–activity relationship study

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Summary

A series of novel 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole derivatives 5(a–m) were synthesized with different substituted aromatic/heterocyclic acid chlorides (R-CO-Cl) and characterized by 1H NMR, LC/MS, FTIR and elemental analyses. All the compounds synthesised were evaluated for their antiproliferative activity by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The antiproliferative effects of the synthesised compounds were tested against viable human skin fibroblast cells and carcinoma cells namely HeLa cells, HT-29 cells, MCF-7 cells, HepG-2 cells by adopting positive and negative control. The importance of the aromatic and heterocyclic moiety was confirmed. From the SAR studies, it reveals that, the substitution at N-terminal of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole by the heterocyclic ring plays a dominant role and was responsible for the antiproliferative activity. Among the synthesized compounds 5a, 5d and 5k have showed potent antiproliferative activity on all the carcinoma cells tested.

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Acknowledgments

The authors are grateful to Council of Scientific and Industrial Research (CSIR), New Delhi for financial support under the project 01(1904)/03/EMR-II 2004, CSIR-SRF to K. Vinaya order No. 09/119(0172)2K8 EMR-I, Elemental Analysis and IR spectroscopic data were obtained from instruments funded by DST-FIST and UGC-SAP (phase I) No.F.540/10/DRS/2004-05 (SAP-I) is greatly acknowledged.

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Authors and Affiliations

  1. Department of Studies in Chemistry, University of Mysore, Manasagangotri, Mysore, 570006, India

    S. B. Benaka Prasad, K. Vinaya, C. S. Ananda Kumar & K. S. Rangappa

  2. Department of Biological Sciences, National University of Singapore, Singapore, Singapore

    Sanjay Swarup

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  1. S. B. Benaka Prasad
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  2. K. Vinaya
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  3. C. S. Ananda Kumar
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  4. Sanjay Swarup
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  5. K. S. Rangappa
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Correspondence to K. S. Rangappa.

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Benaka Prasad, S.B., Vinaya, K., Ananda Kumar, C.S. et al. Synthesis of novel 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole derivatives as antiproliferative agents: A structure–activity relationship study. Invest New Drugs 27, 534–542 (2009). https://doi.org/10.1007/s10637-008-9205-5

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