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Synthesis and Theoretical Study of Novel Imidazo[4,5-b]pyrazine-Conjugated Benzamides as Potential Anticancer Agents

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Abstract

A green synthetic protocol has been developed for the synthesis of imidazo[4,5-b]pyrazine-conjugated benzamides in 80–85% yield via one-pot three-component reaction of phthalic anhydride, substituted anilines, and pyrazine-2,3-diamine in the presence of phosphoric acid as catalyst in water at 95–100°C for 100–120 min. The proposed protocol has the advantages of mild reaction conditions, good yields, short reaction times, and environmental friendliness. The products have been isolated as clean compounds without using column chromatography. The synthesized imidazo[4,5-b]pyrazine-conjugated benzamides were tested for their anticancer activity against liver and ovarian cancer cell lines (HepG2 and HeLa) with IC50 values ranging from 9.8 to 100 µM. Molecular modeling studies revealed the crucial binding interactions of the target protein and the synthesized ligands. In addition, permeability and bioavailability properties have been predicted along with molecular descriptors such as shape index, molecular complexity, and molecular flexibility. The insights drawn from these studies, would help us to design better potent analogs in the future.

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REFERENCES

  1. Chebanov, V.A., Muravyova, E.A., Desenko, S.M., Musatov, V.I., Knyazeva, I.V., Shishkina, S.V., Shishkin, O.V., and Kappe, C.O., J. Comb. Chem., 2006, vol. 8, p. 427. https://doi.org/10.1021/cc060021a

    Article  CAS  PubMed  Google Scholar 

  2. Nilsson, B.L. and Overman, L.E., J. Org. Chem., 2006, vol. 71, p. 7706. https://doi.org/10.1021/jo061199m

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Chebanov, V.A., Saraev, V.E., Desenko, S.M., Chernenko, V.N., Shishkina, S.V., Shishkin, O.V., Kobzar, K.M., and Kappe, C.O., Org. Lett., 2007, vol. 9, p. 1691. https://doi.org/10.1021/ol070411l

    Article  CAS  PubMed  Google Scholar 

  4. De Silva, R.A., Santra, S., and Andreana, P.R., Org. Lett., 2008, vol. 10, p. 4541. https://doi.org/10.1021/ol801841m

    Article  CAS  PubMed  Google Scholar 

  5. Maddila, S., Gangu, K.K., Maddila, S.N., and Jonnalagadda, S.B., Mol Diversity, 2017, vol. 21, p. 247. https://doi.org/10.1007/s11030-016-9708-5

    Article  CAS  Google Scholar 

  6. Gangu, K.K., Maddila, S., and Jonnalagadda, S.B., New J. Chem., 2017, vol. 41, p. 6455. https://doi.org/10.1039/C7NJ00855D

    Article  Google Scholar 

  7. Bhaskaruni, S.V.H.S., Maddila, S., Zyl, W.E., and Jonna­lagadda, S.B., Catal. Commun., 2017, vol. 100, p. 24. https://doi.org/10.3390/molecules23071648

    Article  CAS  Google Scholar 

  8. Shabalala, S., Maddila, S., Zyl, W.E., and Jonnala­gadda, S.B., Catal. Commun., 2016, vol. 79, p. 21. https://doi.org/10.1039/C8RA01994K

    Article  CAS  Google Scholar 

  9. Gangu, K.K., Maddila, S., Maddila, S.N., and Jonna­lagadda, S.B., RSC Adv., 2017, vol. 7, p. 423. https://doi.org/10.1039/c6ra25372e

    Article  CAS  Google Scholar 

  10. Al’-Assar, F., Zelenin, K.N., Lesiovskaya, E.E., Bezhan, I.P., and Chakchir, B.A., Pharm. Chem. J., 2002, vol. 36, p. 598. https://doi.org/10.1023/A:1022665331722

    Article  Google Scholar 

  11. Rambhau, P.G. and Ambarsing, P.R., Drug Invent. Today, 2013, vol. 5, p. 148. https://doi.org/10.1016/j.dit.2013.05.010

    Article  CAS  Google Scholar 

  12. Alexander, D., Wei, W., and Kan, W., Chem. Rev., 2012, vol. 112, p. 3083. https://doi.org/10.1021/cr100233r

    Article  CAS  Google Scholar 

  13. Miniyar, P.B., Murumkar, P.R., Patil, P.S., Barmade, M.A., and Bothara, K.G., Mini-Rev. Med. Chem., 2013, vol. 13, p. 1607. https://doi.org/10.2174/1389557511313110007

    Article  CAS  PubMed  Google Scholar 

  14. Zhao, F., Zhang, J., Zhang, L., Shi, C., Xia, G., Yu, J., and Liu, Y., Bioorg. Med. Chem., 2016, vol. 24, p. 4281. https://doi.org/10.1016/j.bmc.2016.07.019

    Article  CAS  PubMed  Google Scholar 

  15. John, C., Harrington, B., O’Brien, S., Jones, J.A., Schuh, A., Devereux, S., Chaves, J., and Wierda, G., N. Engl. J. Med., 2016, vol. 374, p. 323. https://doi.org/10.1056/NEJMoa1509981

    Article  CAS  Google Scholar 

  16. Mulvihill, M.J., Cooke, A., Rosenfeld-Franklin, M., Buck, E., Foreman, K., Landfair, D., O’Connor, M., Pirritt, C.J., Sun, Y., Yao, Y., Arnold, L.D., Gibson, N.W., and Ji, Q.-Sh., Future Med. Chem., 2009, vol. 16, p. 1153. https://doi.org/10.4155/fmc.09.89

    Article  Google Scholar 

  17. Kirk, D. and Baumgardner, M., Bioorg. Med. Chem. Lett., 2014, vol. 24, p. 4714. https://doi.org/10.1016/j.bmcl.2014.08.008

    Article  CAS  Google Scholar 

  18. Patinote, C., Karroum, N.B., Moarbess, G., Deleuze-Masquefa, C., Hadj-Kaddour, K., Cuq, P., and Kassab, I., Eur. J. Med. Chem., 2017, vol. 138, p. 909. https://doi.org/10.1016/j.ejmech.2017.07.021

    Article  CAS  PubMed  Google Scholar 

  19. Ghanbari-Ardestani, S., Khojasteh-Band, S., Zaboli, M., Hassani, Z., Mortezavi, M., Mahani, M., and Torkzadeh-Mahani, M., J. Mol. Liq., 2019, vol. 292, article ID 111318. https://doi.org/10.1016/j.molliq.2019.111318

  20. Wallace, A.C., Laskowski, R.A., and Thornton, J.M., Protein Eng., Des. Sel., 1995, vol. 8, p. 127. https://doi.org/10.1093/protein/8.2.127

    Article  CAS  Google Scholar 

  21. Jarrahpour, A., Fathi, J., Mimouni, M., Hadda, T.B., Sheikh, J., and Chohan, Z., Med. Chem. Res., 2012. vol. 21, p. 1984. https://doi.org/10.1007/s00044-011-9723-0

    Article  CAS  Google Scholar 

  22. Wicker, J.G. and Cooper, R.I., J. Chem. Inf. Model., 2016, vol. 56, p. 2347. https://doi.org/10.1021/acs.jcim.6b00565

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Parvez, A., Meshram, J., Tiwari, V., Sheikh, J., Dongre, R., Youssoufi, M.H., and Ben Hadda, T., Eur. J. Med. Chem., 2010, vol. 45, p. 4370. https://doi.org/10.1016/j.ejmech.2010.06.004

    Article  CAS  PubMed  Google Scholar 

  24. Méndez-Lucio, O. and Medina-Franco, J., Drug Discovery Today, 2017, vol. 22, p. 120. https://doi.org/10.1016/j.drudis.2016.08.009

    Article  CAS  PubMed  Google Scholar 

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ACKNOWLEDGMENTS

K. Kalpana and J. Saranya thank the authorities of Gokaraju Rangaraju Institute of Engineering and Technology (Hyderabad) for providing research facilities.

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Authors and Affiliations

  1. Department of Humanities and Sciences (Chemistry), Gokaraju Rangaraju Institute of Engineering and Technology, 500090, Bachupally Hyderabad, India

    K. Kalpana, J. Saranya & B. Ravi Kiran

  2. Department of Chemistry, Jawaharlal Nehru Technological University, 500085, Kukatpally Hyderabad, India

    R. Syed

  3. AV College of Arts, Science & Commerce, 500029, Domalguda Hyderabad, India

    M. Rafi

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  1. K. Kalpana
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  3. J. Saranya
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Correspondence to K. Kalpana.

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Kalpana, K., Syed, R., Saranya, J. et al. Synthesis and Theoretical Study of Novel Imidazo[4,5-b]pyrazine-Conjugated Benzamides as Potential Anticancer Agents. Russ J Org Chem 57, 1487–1494 (2021). https://doi.org/10.1134/S1070428021090153

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