Abstract
Fourteen new 4-alkyl/aryl-3,5-bis-(carboethoxy/carbomethoxy)-1,4-dihydro-2,6-dimethylpyridines (4a–4n) have been prepared by conventional and microwave irradiation (MWI) methods from a three component reaction mixture viz., alkyl acetoacetate (1), appropriate aldehyde (2) and ammonium acetate (3). The compounds prepared have been purified and characterized by their spectral (FTIR, 1H NMR and MS) data. The two synthetic methods employed have been compared in terms of relative yields and reaction times. On comparison, the MWI method has been found to be easy, simple, eco-friendly, rapid and high yielding. The synthesized compounds have been evaluated for their cytotoxic activity against HT-29 (colon cancer) and MDA-MB (breast cancer) cell lines and MRP1 inhibitory activity using the insect cell membrane MRP 1 ATPase assay. Though some of the compounds could exhibit some degree of cytotoxicity it was found to be low in comparison to standard. Among the compounds tested 4g was relatively better in its MRP1 inhibitory action (IC50 = 16 μM) but not comparable to that of benzbromarone (IC50 = 4 μM).
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Acknowledgments
The authors are grateful to the authorities of Kakatiya University and UCPSc for facilities and encouragement. One of the authors (A.S.N.) is thankful to University Grants Commission (UGC), New Delhi, India for their financial support in the form of Rajiv Gandhi National Fellowship.
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Amgoth, S.N., Porika, M., Abbagani, S. et al. Synthesis, anticancer and MRP1 inhibitory activities of 4-alkyl/aryl-3,5-bis(carboethoxy/carbomethoxy)-1,4-dihydro-2,6-dimethylpyridines. Med Chem Res 22, 147–155 (2013). https://doi.org/10.1007/s00044-012-9994-0
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DOI: https://doi.org/10.1007/s00044-012-9994-0