A novel series of pyrazoline incorporated isoxazole derivatives were designed and synthesized. The synthesized compounds were characterized by 1H NMR, IR and ESI-MS spectra. In addition, all the synthesized compounds were docked with the target human DHFR (PDB ID: 1KMS). Among all the compounds, compound 5-(4-methoxyphenyl)-3-(5-methyl-3-(4-nitrophenyl)isoxazol-4-yl)-4,5-dihydro-1H-pyrazol-1-yl)(phenyl)methanone proved to be the most potent exhibiting the highest binding affinity with a docking score of 153.763. All the synthesized compounds were screened for anticancer activity against human breast cancer cell lines MCF-7 and MDA-MB-231 through MTT assay. Out of all the synthesized compounds (5-(4-methoxyphenyl)-3-(5-methyl-3-(4-nitrophenyl)isoxazol-4-yl)-4,5-dihydro-1H-pyrazol-1-yl)(phenyl)methanone posses good activity with IC50 values ranging from 3–4 μg/mL. Further all the compounds were screened for antitubercular assay against the strain H37Rv and multidrug resistant strain DKU 156, among all four compounds exhibited significant activity at 6.25 µg/mL concentrations. Thus the MIC value may be in between the range of 3.12 and 6.25 µg/mL.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
GBD 2015, 1980–2015: A systematic analysis for the Global Burden of Disease study 2015, Lancet, 2016, vol. 388, pp. 1459–544.
Housman, G., Byler, S., Heerboth, S., Lapinska, K., Longacre, M., Snyder, N., and Sarkar, S., Cancers, 2014, vol. 6, no. 3, pp. 1769–179.
Sysak, A. and Obmińska-Mrukowicz, B., Eur. J. Med. Chem., 2017, vol. 137, pp. 292–309.
Dadmal, T.L., Appalanaidu, K., Kumbhare, R.M., et al., New J. Chem., 2018, vol. 42, no. 19, pp. 15 546–15 551.
Sherifa, M., Abu Bakr, Somaia, S., et al., Res. Chem. Int., 2016, vol. 42, pp. 1387–1399.
Srinivas Burra,Vani Voora, Ch., Prasad Rao, et al., Bioorg. Med. Chem. Lett., 2017, vol. 27, pp. 4314–4318.
Yong, J.P. Lu, C.Z., and Wu, X., Anti-Cancer Agent.Med. Chem., 2015, vol. 15, no. 1, pp. 131–136.
Ahmed Kamal, Surendranadha Reddy, J., Janaki Ramaiah, M., et al., Eur. J. Med. Chem., 2010, vol. 45, pp. 3924–3937.
Basha, S.S., Divya, K., Padmaja, et al., Res. Chem. Int., 2015, vol. 41, no. 12, pp. 10 067–10 083.
Panda, S.S., Chowdary, P.R., and Jayashree, B.S., Ind. J. Pharm. Sci., 2009, vol. 71, no. 6, p. 684.
Radhika Tumma, Harinadha Babu Vamaraju, Madhava Reddy Bommineni, et al., J. Pharm. Res., 2017, vol. 11, no. 7, pp. 895–902.
Yang, Z., Li, P., and Gan, X., Molecules, 2018, vol. 23, no. 7, p. 1798.
Faria, J.V., Vegi, P.F., Miguita, A.G., et al., Bioorg. Med. Chem., 2017, vol. 25, no. 21, pp. 5891–5903.
Naim, M.J., Alam, O., and Farah Nawaz, M., J. Pharm. Biol. Sci., 2016, vol. 8, no. 1, p. 2.
Karrouchi, K., Radi, S., Ramli, Y., et al., Molecules, 2018, vol. 23, no. 1, p. 134.
Balbi, A., Anzaldi, M., Macciò, C., et al., Eur. J. Med. Chem., 2011, vol. 46, no. 11, pp. 5293–5309.
Sondhi, S.M., Kumar, S., Kumar, N., et al.,Med. Chem. Res., 2012, vol, 21, no. 10, pp. 3043–3052.
Kumari, S., Paliwal, S., and Chauhan, R., Synth. Comm., 2014, vol. 44, no. 11, pp. 1521–1578.
Balbi, A., Anzaldi, M., Macciò, C., et al., Eur. J. Med. Chem., 2011, vol. 46, no. 11, pp. 5293–309.
Ansari, A., Ali, A., and Asif, M., New J. Chem., 2017, vol. 41, no. 1, pp. 16–41.
Ahmad, A, Husain, A, Khan, S.A., and Bhandari, A., J. Saudi Chem. Soc., 2016, vol. 20, no. 5, pp. 577–584.
Ali, M.A., Yar, M.S., Kumar, M., and Pandian, G.S., Nat. Prod. Res., 2007, vol. 21, no. 7, pp. 575–579.
Azzali, E., Machado, D., Kaushik, A., Vacondio, F., Flisi, S., Cabassi, C.S., Lamichhane, G., et al., J. Med. Chem., 2017, vol. 60, no. 16, pp. 7108–7122.
Wan, M., Xu, L., Hua, L., Li, A., Li, S., Lu, W., Pang, Y., Cao, C., Liu, X. and Jiao, P., Bioorg. Chem., 2014, vol. 54, pp. 38–43.
The authors are thankful to G. Pulla reddy college of Pharmacy and Osmania University.
This article doesnot contain any studies involving human participants performed by any of the authors and doesnot contain any studies involving animals performed by any of the author.
Conflict of Interests. The authors report no conflicts of interest.
Corresponding author: e-mail: email@example.com.
About this article
Cite this article
Radhika, T., Vijay, A., Harinadha, B.V. et al. Design, Synthesis, Molecular Docking Studies, and Biological Evaluation of Pyrazoline Incorporated Isoxazole Derivatives. Russ J Bioorg Chem 46, 429–437 (2020). https://doi.org/10.1134/S1068162020030152
- binding affinity