Abstract
A series of 18 new 3,4-disubstituted-isothiochromeno[3,4-e][1,2]oxazines 28–45 has been obtained from the 3′,4′-di-substituted-4′H-spiro[isothiochromene-3,5′-isoxazol]-4(1H)-ones 10–27 in refluxing HCl acid/ethanol. A series of 15/18 compounds 28–45 was selected by the National Cancer Institute (NCI, Bethesda, USA) and were evaluated against a full panel of 60 primary human tumor cell lines derived from nine human cancer types, all of which showed antiproliferative activity in the micromolar range. The most active compound number 37 (S722910) showed high potency against all the tested cell lines with a GI50 mean value in the range of 30–80 μM; TGI and LC50 values were 12–16 μM having positive response on 98 and 63 % of the tested cell lines (Breast-MCF7 and NCS-SF-268) respectively.
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Abbreviations
- GI50 :
-
Growth inhibition; the drug concentration resulting in a 50 % reduction in the net protein increase compared with control cells during the drug incubation
- TGI:
-
Cytostatic activity; the drug concentration resulting in total growth inhibition
- LC50 :
-
The concentration of drug resulting in a 50 % reduction in the measured protein at the end of the drug treatment compared with that at the beginning, thus indicating a net loss of cells following treatment
- POM:
-
Petra/Osiris/Molinspiration
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Acknowledgments
This work was supported by the grants from the Ministry of Education of Morocco (PGR-UMP-BH-2005 and PROTARS I). We are indebted to the National Cancer Institute (NCI) of the United States for biologic tests.
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Bennani, B., Kerbal, A., Baba, B.F. et al. Synthesis, characterization, bioactivity, and POM analyses of isothiochromeno[3,4-e][1,2]oxazines. Med Chem Res 22, 4798–4809 (2013). https://doi.org/10.1007/s00044-012-0392-4
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DOI: https://doi.org/10.1007/s00044-012-0392-4