Synthesis and Antitumor Activity of 1,2,4-Triazolo[1,5-a]quinazolines

R. Al-Salahi; M. Marzouk; A.E. Ashour; I. Alswaidan

doi:10.14233/ajchem.2014.16849

Issue

Vol. 26 No. 7 (2014): Vol 26 Issue 7

Issue Published : March 22, 2014

This work is licensed under a Creative Commons Attribution 4.0 International License.

Synthesis and Antitumor Activity of 1,2,4-Triazolo[1,5-a]quinazolines

https://doi.org/10.14233/ajchem.2014.16849

R. Al-Salahi

Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia

M. Marzouk

Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia ;Chemistry of Natural Products Group, Center of Excellence for Advanced Sciences, National Research Center, Dokki, 12622, Cairo, Egypt

A.E. Ashour

Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia

I. Alswaidan

Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia

Corresponding Author(s) : M. Marzouk

msmarzouk@yahoo.co.uk

Asian Journal of Chemistry, Vol. 26 No. 7 (2014): Vol 26 Issue 7
Article Published : March 31, 2014

Abstract

Cytotoxicity of 22 triazoloquinazoline compounds was evaluated in vitro against medulloblastoma (Daoy), hepatocellular carcinoma (HepG2) and melanoma (SK-MEL28) cell lines. This study showed that compounds 17, 18 and 21 exhibited remarkable in vitro cytotoxicity against all tested cell lines. Moreover, it was found that compounds 10, 17, 6, 18, 21, 7 and 19 are active against Daoy cell line with IC₅₀ values of 1.29, 2.93, 5.53, 6.14, 6.59, 9.71 and 19 μg/mL, respectively, as compared to that of the reference drug dasatinib (7.26 μg/mL). The HepG2 cell line was affected by compounds 17, 6, 21, 19 and 18 with IC₅₀ values of 4.52, 11.33, 14.69, 16.96 and 24.49 μg/mL, respectively, relative to that of dasatinib (8.21 μg/mL). In addition, compounds 17, 18 and 21 have shown significant antiproliferative activity against SK-MEL28 with IC₅₀ values of 3.88, 13.85 and 14.96, respectively, relative to an IC₅₀ value of 23.83 μg/mL of the reference drug. It is worth mentioning that compounds 6, 10, 17, 18 and 21 are more potent than the reference drug against Daoy cell. In the same manner, 17, 18 and 21 revealed higher cytotoxicity than dasatinib against SK-MEL28 cells. Notably, compound 17 was also more potent than the reference drug against HepG2 cells. In the term of selectivity, compound 10 was found to possess the highest selectivity, as it was active only against Daoy cells. These compounds could be useful as templates for further development through their structural modification to design more potent antitumor agents.

Keywords

Antitumor 1 2 4-Triazolo[1 5-a]quinazolines Daoy HepG2 SK-MEL28

Al-Salahi, R., Marzouk, M., Ashour, A., & Alswaidan, I. (2014). Synthesis and Antitumor Activity of 1,2,4-Triazolo[1,5-a]quinazolines. Asian Journal of Chemistry, 26(7), 2173–2176. https://doi.org/10.14233/ajchem.2014.16849

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B.S.P. Sandor Eckhardt, Curr. Med. Chem. Anticancer Agents, 2, 419 (2002); doi:10.2174/1568011024606389.

J.C. Medina, B. Shan, H. Beckmann, R.P. Farrell, D.L. Clark, R. Marc Learned, D. Roche, A. Li, V. Baichwal, C. Case, P.A. Baeuerle, T. Rosen and J.C. Jaen, Bioorg. Med. Chem. Lett., 8, 2653 (1998); doi:10.1016/S0960-894X(98)00477-6.

A.A.M. Abdel-Aziz, Eur. J. Med. Chem., 42, 614 (2007); doi:10.1016/j.ejmech.2006.12.003.

H.S. Hwang, E.Y. Moon, S.K. Seong, C.H. Choi, C.H. Chung, S.H. Jung and S. Yoon, J. Anticancer Res., 19, 5087 (1999).

H.-Y. Park Choo, M. Kim, S.K. Lee, S. Woong Kim and I. Kwon Chung, Bioorg. Med. Chem., 10, 517 (2002); doi:10.1016/S0968-0896(01)00299-1.

S.T. Al-Rashood, I.A. Aboldahab, M.N. Nagi, L.A. Abouzeid, A.A.M. Abdel-Aziz, S.G. Abdel-Hamide, K.M. Youssef, A.M. Al-Obaid and H.I. El-Subbagh, Bioorg. Med. Chem., 14, 8608 (2006); doi:10.1016/j.bmc.2006.08.030.

A.M. Al-Obaid, S.G. Abdel-Hamide, H.A. El-Kashef, A.A.-M. Abdel-Aziz, A.S. El-Azab, H.A. Al-Khamees and H.I. El-Subbagh, Eur. J. Med. Chem., 44, 2379 (2009); doi:10.1016/j.ejmech.2008.09.015.

F.A.M. Al-Omary, L.A. Abou-zeid, M.N. Nagi, E.-S.E. Habib, A.A.-M. Abdel-Aziz, A.S. El-Azab, S.G. Abdel-Hamide, M.A. Al-Omar, A.M. Al-Obaid and H.I. El-Subbagh, Bioorg. Med. Chem., 18, 2849 (2010); doi:10.1016/j.bmc.2010.03.019.

F. Barlesi, C. Tchouhadjian, C. Doddoli, P. Villani, L. Greillier, J.-P. Kleisbauer, P. Thomas and P. Astoul, Fundam. Clin. Pharmacol., 19, 385 (2005); doi:10.1111/j.1472-8206.2005.00323.x.

I. Kostova, Curr. Med. Chem. Anticancer Agents, 5, 29 (2005); doi:10.2174/1568011053352550.

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T. Abdollahi, N.M. Robertson, A. Abdollahi and G. Litwack, Cancer Res., 63, 4521 (2003).

L.J. Lombardo, F.Y. Lee, P. Chen, D. Norris, J.C. Barrish, K. Behnia, S. Castaneda, L.A.M. Cornelius, J. Das, A.M. Doweyko, C. Fairchild, J.T. Hunt, I. Inigo, K. Johnston, A. Kamath, D. Kan, H. Klei, P. Marathe, S. Pang, R. Peterson, S. Pitt, G.L. Schieven, R.J. Schmidt, J. Tokarski, M.-L. Wen, J. Wityak and R.M. Borzilleri, J. Med. Chem., 47, 6658 (2004); doi:10.1021/jm049486a.

R. Al-Salahi and D. Geffken, J. Heterocycl. Chem., 48, 656 (2011); doi:10.1002/jhet.574.

R. Al-Salahi and D. Geffken, Heterocycles, 81, 1843 (2010); doi:10.3987/COM-10-11976.

R. Al-Salahi and D. Geffken, Molecules, 15, 7016 (2010); doi:10.3390/molecules15107016.

R. Al-Salahi and D. Geffken, Synth. Commun., 41, 3512 (2011); doi:10.1080/00397911.2010.518780.

R. Al-Salahi, K.-E. El-Tahir, I. Alswaidan, N. Lolak, M. Hamidaddin and M. Marzouk, Chem. Cent. J., 8, 3 (2014); doi:10.1186/1752-153X-8-3.

Issue

Vol. 26 No. 7 (2014): Vol 26 Issue 7

Synthesis and Antitumor Activity of 1,2,4-Triazolo[1,5-a]quinazolines

Corresponding Author(s) : M. Marzouk

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