Abstract
A series of novel 5-phenyl-substituted 1,3,4-thiadiazole-2-amines were designed, synthesized, and screened for their antitumor and antitubercular activities. The target compounds were synthesized starting from isocyanates and acid hydrazides by conventional and microwave-assisted protocols. The structures of the products were confirmed by 1H NMR, 13C NMR, high-resolution mass spectrometry, and IR spectroscopy and elemental analysis. Some of the synthesized compounds showed significant invitro antitumor activities against breast cancer and normal human cell lines. Among them, N-benzyl-5-(4-fluorophenyl)-, N-benzyl-5-(4-nitrophenyl)-, and 5-phenyl-N-(p-tolyl)-1,3,4-thiadiazole-2-amines demonstrated higher inhibitory activities against the MDA-MB-231 cell line than the cisplatin control (IC50 3.3 ώM). N-Benzyl-5-(4-methoxyphenyl)-, 5-phenyl-N-[4-(trifluoromethyl)phenyl]methyl-, N-benzyl-5-(4-fluorophenyl)-, and N-benzyl-5-(4-nitrophenyl)-1,3,4-thiadiazole-2-amines exhibited high inhibitory activities against the HEK293T cell line (IC50 52.63, 42.67, 34.71, and 33.74 ώM, respectively), which were higher compared to the cisplatin control. In antitubercular activity testing against mycobacterium smegmatis MC155, 5-phenyl-N-[4-(trifluoromethyl)-phenyl]methyl-1,3,4-thiadiazole-2-amine proved to be a more potent agent (MIC 26.46 ώg/mL) compared to the Isoniazid control (12 ώg/mL). Potential bioactivities of the synthesized compounds were computed using Molinspiration and Molsoft software tools.
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Amir, M. and Shikha, K., Eur. J. Med. Chem., 2004, vol. 39, p. 535. doi https://doi.org/10.1016/j.ejmech.2004.02.008
Kumar, H., Javed, S.A., Khan, A.S., and Amir, M., Eur. J. Med. Chem., 2008, vol. 43, p. 2688. doi https://doi.org/10.1016/j.ejmech.2008.01.039
Li, Y., Geng, J., Liu, Y., Yu, S., and Zhao, G., Chem. Med. Chem., 2013, vol. 8, p. 271. doi https://doi.org/10.1002/cmdc.201200355
Hu, Y., Li, C.Y., Wang, X.M., Yang, Y.H., and Zhu, H.L., Chem. Rev., 2014, vol. 114, p. 5572. doi https://doi.org/10.1021/cr400131u
Michael, R., Stillings, A.P., and Welbourn, D.S.W., J. Med. Chem., 1986, vol. 29, p. 2280. doi https://doi.org/10.1021/jm00161a025
Xu, W.M., Han, F.F., He, M., Hu, D.Y., He, J., Yang, S., and Song, B.A. J. Agric. Food Chem., 2012, vol. 60, p. 1036. doi https://doi.org/10.1021/jf203772d
Harfenist, M., Heuser, D.J., Joyner, C.T., Batchelor, J.F., and White, H.L., J. Med. Chem., 1996, vol. 39, p. 1857. doi https://doi.org/10.1021/jm950595m
Liu, F., Luo, X.Q., Song, B.A., Bhadury, P.S., Yang, S., Jin, L.H., Xue, W., and Hu, D.Y., Bioorg. Med. Chem., 2008, vol. 16, p. 3632. doi https://doi.org/10.1016/j.bmc.2008.02.006
Chen, C.J., Song, B.A., Yang, S., Xu, G.F., Bhadury, P.S., Jin, L.H., Hu, D.Y., Li, Q.Z., Liu, F., Xue, W., Lu, P., and Chen, Z., Bioorg. Med. Chem. Lett., 2007, vol. 15, p. 3981. doi https://doi.org/10.1016/j.bmc.2007.04.014
Ahsan, M.J., Samy, J.G., Khalilullah, H., Nomani, M.S., Saraswat, P., Gaur, R., and Singh, A., Bioorg. Med. Chem. Lett., 2011, vol. 21, p. 7246. doi https://doi.org/10.1016/j.bmcl.2011.10.057
Tsukamoto, K., Suno, M., Igarashi, K., Kozai, Y., and Sugino, Y., Cancer Res., 1975, vol. 35, p. 2631. doi https://doi.org/10.1134/S1068162014020083
Supuran, C.T. and Scozzafava, A., Eur. J. Med. Chem., 2000, vol. 35, p. 867. doi https://doi.org/10.1016/S0223-5234(00)00169-0
Vergne, F., Bernardelli, P., Lorthiois, E., Pham, N., Proust, E., Oliveira, C., Mafroud, A.K., Royer, F., Wriggles Worth, R., Schellhaas, J.K., Barvian, M.R., Moreau, F., Idrissi, M., Tertre, A., Bertin, B., Coupe, M., Berna, P., and Soulard, P., Bioorg. Med. Chem. Lett., 2004, vol.14, p. 4607. doi https://doi.org/10.1016/j.bmcl.2004.07.009
Rajak, H., Agarawal, A., Parmar, P., Thakur, B.S., Veerasamy, R., Sharma, P.C., and Kharya, M.D., Bioorg. Med. Chem. Lett., 2011, vol.21, p. 5735. doi https://doi.org/10.1016/j.bmcl.2011.08.022
Jung, K.Y., Kim, S.K., Gao, Z.G., Gross, A.S., Melman, N., Jacobson, K.-A., and Kim, Y.-C., Bioorg. Med. Chem., 2004, vol.12, p. 613. doi https://doi.org/10.1016/j.bmc.2003.10.041
Macaev, F., Ribkovskaia, Z., Pogrebnoi, S., Boldescu, V., Rusu, G., Shvets, N., Dimoglo, A., Geronikaki, A., and Reynolds, R., Bioorg. Med. Chem., 2011, vol. 19, p. 6792. doi https://doi.org/10.1016/j.bmc.2011.09.038
Rakesh, R., Prabhakar, S., and Shirodkar, Y., Der. Pharma. Chemica., 2009, vol. 1, p. 130.
Refsgaard, H.H.F., Jensen, B.F., Brockhoff, P.B., Padkjaer, S.B., Guldbrandt, M., and Christensen, M.S., J. Med. Chem., 2005, vol. 48, p. 805. doi https://doi.org/10.1021/jm049661n
Muegge, I., Med. Res. Rev., 2003, vol. 23, p. 302. doi https://doi.org/10.1002/med.10041
Ertl, P., Rohde, B., and Selzer, P., J. Med. Chem., 2000, vol. 43, p. 3714. doi https://doi.org/10.1021/jm000942e
Veber D.F., Johnson, S.R., Cheng, H.Y., Smith, B.R., Ward, K.W., and Kapple, K.D., J. Med. Chem., 2002, vol. 45, p. 2615. doi https://doi.org/10.1021/jm020017n
Gerlier, D. and Thomasset, N., J. Immunol. Methods., 1986, vol. 94, p. 57. doi https://doi.org/10.1016/0022-1759(86)90215-2
Abu Bakar, M.F., Maryati, M., Rahmat, A., Burr, S.A., and Fry, J.R., Food. Chem. Toxicol., 2010, vol. 48, p. 1688. doi https://doi.org/10.1016/j.fct.2010.03.046
Wang R.X., Fu, Y., and Lai, L.H., J. Chem. Inf. Comput. Sci., 1997, vol. 37, p. 615. doi https://doi.org/10.1021/ci960169p
Antimycobacterial Susceptibility Testing for Myco-bacterium tuberculosis. Proposed Standard M24-T, National Committee for Clinical Laboratory Standards, Villanova, PA, 1995.
Smith, I., Clin. Microbiol. Rev., 2003, vol. 16, p. 463. doi https://doi.org/10.1128/CMR.16.3.463-496.2003
Pfaller, M.A. and Barry, A.L., J. Clin. Microbiol., 1994, vol. 32, p. 1992.
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Chandra Sekhar, D., Venkata Rao, D.V., Tejeswara Rao, A. et al. Design and Synthesis of 1,3,4-Thiadiazole Derivatives as Novel Anticancer and Antitubercular Agents. Russ J Gen Chem 89, 770–779 (2019). https://doi.org/10.1134/S1070363219040224
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DOI: https://doi.org/10.1134/S1070363219040224