With evident biological importance, a new series of pyrazolo[3,4-d]pyrimidines 3a,3b and 4a,4b were synthesized via the formation of pyrazol-3-one 2a and 2b substrates. All compounds were evaluated for in vitro cytotoxic activity against MCF-7 (breast adenocarcinoma) and A549 (lung cancer) cell lines. The obtained results showed that pyrazolo[3,4-d] pyrimidin-4-ol 3a bearing phenyl group at N-1 and p-C6H4 at C-6, and 4b with dinitrophenyl at N-1 and furanyl moiety at C-6 had better inhibitory activity against MCF-7 with IC50 values in a micromolar range as compared to other substrates. The synthesized compounds can be considered as new candidates for further optimization as anticancer agents.
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References
S. Cherukupalli, B. Chandrasekaran, V. Krystof, et al., Bioorg. Chem., 79, 46 – 59 (2018).
G. M. Nitulescu, C. Draghici, O. T. Olaru, et al., Bioorg. Med. Chem., 23(17), 5799 – 5808 (2015).
A. Molinari, A. L. Fallacara, S. Di Maria, et al., Bioorg. Med. Chem. Lett., 28(21), 3454 – 3457 (2018).
A. A. Gaber, A. H. Bayoumi, A. M. El-Morsy, et al., Bioorg. Chem., 80, 375 – 395 (2018).
M. Huang, A. Shen, J. Ding, and M. Geng, Trends Pharmacol. Sci., 35(1), 41 – 50 (2014).
N. Pravin, V. Devaraji, and N. Raman, Int. J. Biol. Macromol., 79, 837 – 855 (2015).
C. Bagul, G. K. Rao, V. K. K. Makani, et al., MedChemComm, 8(9), 1810 – 1816 (2017).
K. R. A. Abdellatif and R. B. Bakr, Bioorg. Chem., 78, 341 – 357 (2018).
A. Rahmouni, S. Souiei, M. A. Belkacem, et al., Bioorg. Chem., 66, 160 – 168 (2016).
T. S. Reddy, H. Kulhari, V. G. Reddy, et al., Eur. J. Med. Chem., 101, 790 – 805 (2015).
H. A. Abd El Razik, M. Mroueh, W. H. Faour, et al., Chem. Biol. Drug Des., 90(1), 83 – 96 (2017).
D. J. Richard, J. C. Verheijen, K. Curran, et al., Bioorg. Med. Chem. Lett., 19(24), 6830 – 6835 (2009).
J. B. Shi, W. J. Tang, X. B. Qi, et al., Eur. J. Med. Chem., 90, 889 – 896 (2015).
S. Cherukupalli, B. Chandrasekaran, R. R. Aleti, et al., J. Mol. Struct., 1176, 538 – 551 (2019).
K. J. Curran, J. C. Verheijen, J. Kaplan, et al., Bioorg. Med. Chem. Lett., 20(4), 1440 – 1444 (2010).
N. Zheng, J. Pan, Q. Hao, et al., Bioorg. Med. Chem., 26(8), 2165 – 2172 (2018).
M. Ding, H. Wang, C. Qu, et al., Cancer Lett., 432, 47 – 55 (2018).
P. Muthuraja, V. Veeramani, S. Prakash, et al., Bioorg. Chem., 84, 493 – 504 (2019).
M. M. Ghorab, F. A. Ragab, S. I. Alqasoumi, et al., Eur. J. Med. Chem., 45(1), 171 – 178 (2010).
M. A. Abdelgawad, R. B. Bakr, O. A. Alkhoja, and W. R. Mohamed, Bioorg. Chem., 66, 88 – 96 (2016).
S. Cherukupalli, G. A. Hampannavar, S. Chinnam, et al., Bioorg. Med. Chem., 26(2), 309 – 339 (2018).
J. A. Markwalder, M. R. Arnone, P. A. Benfield, et al., J. Med. Chem., 47(24), 5894 – 5911 (2004).
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The authors are thankful to the Deanship of Scientific Research, King Abdulaziz University, Jeddah, Saudi Arabia (grant number, G-1436-363-328) for great support of this work.
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Alharthy, R.D. Design and Synthesis of Novel Pyrazolo[3,4-d]Pyrimidines: In Vitro Cytotoxic Evaluation and Free Radical Scavenging Activity Studies. Pharm Chem J 54, 273–278 (2020). https://doi.org/10.1007/s11094-020-02190-2
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DOI: https://doi.org/10.1007/s11094-020-02190-2