Cytotoxic Effects of Thiazolo[3,2-C]Pyrimidines Against Mcf-7 And Hepg2/C3a Carcinoma Cell Lines

Year 2018, Volume: 46 Issue: 2, 237 - 246, 03.06.2018

Arzu Birinci Yıldırım Esra Mutlu Muhammet Yıldırım

Abstract

I
n the present study, a series of thiazolo[3,2-c]pyrimidines (4,5) have been produced via simple and efficient
synthetic method and their in vitro cytotoxicities have been performed on human breast (MCF-7) and
hepatocellular (HEPG2/C3A) adenocarcinoma cell lines. The results of these in vitro tests revealed that at
least five of thiazolo[3,2-c]pyrimidines exhibited strong cytotoxic effects at very low concentrations, which
were very similar or lower than that of reference anticancer agent, 5-FU, against MCF-7 and HEPG2/C3A cancer
cell lines.

Keywords

Anticancer, breast cancer, Mannich cyclisation, thiazolopyrimidines

References

• D. Peer, J.M. Karp, S. Hong, O.C. Farokhzad, R. Margalit, R. Langer, Nanocarriers as an emerging platform for cancer therapy, Nat. Nanotechnol., 2 (2007) 751-760.
• F. Arcamone, Doxorubicin: anticancer antibiotics, (2012) Elsevier, New York, NY, USA.
• A. Nagy, P. Armatis, A.V. Schally, High yield conversion of doxorubicin to 2-pyrrolinodoxorubicin, an analog 500-1000 times more potent: structure-activity relationship of daunosamine-modified derivatives of doxorubicin, Proceedings of the National Academy of Sciences, 93 (1996) 2464-2469.
• G. Rodriguez-Berna, M.J.D. Cabañas, V. MangasSanjuán, M. Gonzalez-Alvarez, I. Gonzalez-Alvarez, I. Abasolo, S. Schwartz Jr, M. Bermejo, A. Corma, Semisynthesis, Cytotoxic Activity, and Oral Availability of New Lipophilic 9-Substituted Camptothecin Derivatives, ACS Med. Chem. Lett., 4 (2013) 651-655.
• M.C. Wani, H.L. Taylor, M.E. Wall, P. Coggon, A.T. McPhail, Plant antitumor agents. VI. Isolation and structure of taxol, a novel antileukemic and antitumor agent from Taxus brevifolia, J. Am. Chem. Soc., 93 (1971) 2325-2327.
• P.B. Schiff, J. Fant, S.B. Horwitz, Promotion of microtubule assembly in vitro by taxol, Nature, 277 (1979) 665-667.
• D.B. Longley, D.P. Harkin, P.G. Johnston, 5-fluorouracil: mechanisms of action and clinical strategies, Nature reviews. Cancer, 3 (2003) 330-338.
• B. Shi, B. Yaremko, G. Hajian, G. Terracina, W.R. Bishop, M. Liu, L.L. Nielsen, The farnesyl protein transferase inhibitor SCH66336 synergizes with taxanes in vitro and enhances their antitumor activity in vivo, Cancer Chemoth. Pharm., 46 (2000) 387-393.
• O. Cuvillier, V. Nava, S. Murthy, L. Edsall, T. Levade, S. Milstien, S. Spiegel, Sphingosine generation, cytochrome C release, and activation of caspase-7 in doxorubicin-induced apoptosis of MCF7 breast adenocarcinoma cells, Cell Death. Differ., 8 (2001) 162-171.
• F.W. Symmans, Breast cancer response to paclitaxel in vivo, Drug Resist. Update, 4 (2001) 297-302.
• J. Wichmann, G. Adam, S. Kolczewski, V. Mutel, T. Woltering, Structure-activity relationships of substituted 5H-thiazolo[3,2-a]pyrimidines as group 2 metabotropic glutamate receptor antagonists, Bioorg. Med. Chem. Lett., 9 (1999) 1573-157.
• F.A. Al-Omary, G.S. Hassan, S.M. El-Messery, H.I. ElSubbagh, Substituted thiazoles V. Synthesis and antitumor activity of novel thiazolo[2,3-b]quinazoline and pyrido[4,3-d] thiazolo[3,2-a] pyrimidine analogues, Eur. J. Med. Chem., 47 (2012) 65-72.
• S. Fatima, A. Sharma, R. Saxena, R. Tripathi, S.K. Shukla, S.K. Pandey, R. Tripathi, R.P. Tripathi, One pot efficient diversity oriented synthesis of polyfunctional styryl thiazolopyrimidines and their bio-evaluation as antimalarial and anti-HIV agents, Eur. J. Med. Chem., 55 (2012) 195-204.
• M. Yıldırım, D. Çelikel,Y. Dürüst, D.W. Knight, B.M. Kariuki, A rapid and efficient protocol for the synthesis of novel nitrothiazolo[3,2-c]pyrimidines via microwave-mediated Mannich cyclisation, Tetrahedron, 70 (2014) 2122-2128.
• E. Flefel, M. Salama, M. El-Shahat, M. El-Hashash, A. El-Farargy, A novel synthesis of some new pyrimidine and thiazolopyrimidine derivatives for anticancer evaluation, Phosphorus Sulfur., 182 (2007) 1739-1756.
• R. Lin, S.G. Johnson, P.J. Connolly, S.K. Wetter, E. Binnun, T.V. Hughes, W.V. Murray, N.B. Pandey, S.J. Moreno-Mazza, M. Adams, Synthesis and evaluation of 2,7-diamino-thiazolo[4,5-d]pyrimidine analogues as anti-tumor epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, Bioorg. Med. Chem. Lett., 19 (2009) 2333-2337.
• B. Singh, S.K. Guru, S. Kour, S.K. Jain, R. Sharma, P.R. Sharma, S.K. Singh, S. Bhushan, S.B. Bharate, R.A. Vishwakarma, Synthesis, antiproliferative and apoptosis-inducing activity of thiazolo[5,4-d] pyrimidines, Eur. J. Med. Chem., 70 (2013) 864-874.
• T.A.A. Yahya, J.H. Abdullah, M.A.H. Al-Ghorafi, S.H. Yassin, H.M. Almahbshi, Synthesis of some arylidene derivatives of thiazolopyrimidineas anticancer, Der Pharma Chemica, 7 (2015) 106-110.
• N.A. Abdel-Hafez, S.F. Mohamed, F.A. El-Hag, U.W. Hawas, H.M. Awad, Synthesis and Cytotoxicity Evaluation of Some New Pyrimidinethione and Thiazolopyrimidine Derivatives Linked to N-Propylpiperidone, Der Pharma Chemica, 8 (2016) 57-66.
• B. Kuppast, H. Fahmy, Thiazolo[4,5-d]pyrimidines as a privileged scaffold in drug discovery, Eur.J. Med. Chem., 113 (2016) 198-213.
• S. Kolb, O. Mondésert, M.L. Goddard, D. Jullien, B.O. Villoutreix, B. Ducommun, C. Garbay, E. Braud, Development of novel thiazolopyrimidines as CDC25B phosphatase inhibitors, ChemMedChem, 4 (2009) 633-648.
• A.A. Abu-Hashem, M.M. Youssef, H.A. Hussein, Synthesis, antioxidant, antituomer activities of some new thiazolopyrimidines, pyrrolothiazolopyrimidines and triazolo pyrrolothiazolopyrimidines derivatives, J.Chil. Chem. Soc., 58 (2011) 41-48.
• M. Yıldırım, D. Çelikel, A rapid access to novel and diverse 3-oxothiazolo[3,2-c]pyrimidine-8- carboxylates using multicomponent Mannich cyclisation reactions, Mol. Divers., 19 (2015) 1-13.
• M. Stojanović, R. Marković, E. Kleinpeter, M. BaranacStojanović, endo-Mode cyclizations of vinylogous N-acyliminium ions as a route to the synthesis of condensed thiazolidines, Tetrahedron, 67 (2011) 9541- 9554.
• D. Çelikel, Synthesis of new thiazolopyrimidine, thiazolo(imidazolo) pyridinone derivatives via multicomponent reactions M.Sc. Master Thesis, (2015) Abant İzzet Baysal University, Bolu,Turkey.
• F.P. Karakas, A.B. Yildirim, R. Bayram, M.Z. Yavuz, A. Gepdiremen, A.U. Turker, Antiproliferative activity of some medicinal plants on human breast and hepatocellular carcinoma cell lines and their phenolic contents, Trop. J. Pharm. Res., 14 (2015) 1787-1795.
• M.M. Kamel, H.I. Ali, M.M. Anwar, N.A. Mohamed, A.M. Soliman, Synthesis, antitumor activity and molecular docking study of novel sulfonamideSchiff’s bases, thiazolidinones, benzothiazinones and their C-nucleoside derivatives, Eur. J. Med. Chem., 45 (2010) 572-580.
• X. Liu, W. Wei, S. Huang, S-S. Lin, X. Zhang, C. Zhang, Y. Du, G. Ma, M. Li, S. Mann, Bio-inspired protein– gold nanoconstruct with core–void–shell structure: beyond a chemo drug carrier, J. Mater. Chem. B., 1 (2013) 3136-3143.
• G.S. Hassan, Synthesis and antitumor activity of certain new thiazolo[2,3-b]quinazoline and thiazolo[3,2-a] pyrimidine analogs, Med. Chem. Res., 23 (2014) 388-401.
• L. Shen, J. Hu, H. Wang, A. Wang, Y. Lai, Y. Kang, Synthesis and biological evaluation of novel uracil and 5-fluorouracil-1-yl acetic acid-colchicine conjugate, Chem. Res. Chinese. U., 31(2015) 367-371.
• P.N. Le, N.H. Nguyen, C.K. Nguyen, N.Q. Tran, Smart dendrimer-based nanogel for enhancing 5-fluorouracil loading efficiency against MCF7 cancer cell growth, B. Mater. Sci., 39 (2016) 1493-1500.
• J.M. Gichumbi, B. Omondi, G. Lazarus, M. Singh, N. Shaikh, H.Y. Chenia, H.B. Friedrich, Influence of Halogen Substitution in the Ligand Sphere on the Antitumor and Antibacterial Activity of Half sandwich Ruthenium (II) Complexes [RuX( 6 arene) (C5H4N2 CH=N Ar)]+, Z. Anorg. Allg. Chem., 643 (2017) 699-711.
• I.M. Abbas, S.M. Gomha, M.M. Elaasser, B.K. Mabrouk, Synthesis and characterisation of some novel fused thiazolo[3,2-a]pyrimidinones and pyrimido[2,1-b][1,3] thiazinones, J. Chem. Res., 39 (2015) 719-723.
• S. Awad, O. Fathalla, J. Wietrzyk, M. Milczarek, A. Soliman, M.S. Mohamed, Synthesis of new pyrimidine derivatives and their antiproliferative activity against selected human cancer cell lines, Res. Chem. Intermediat., 41 (2015) 1789-1801.
• S.M. Rida, S.A. El-Hawash, H.T. Fahmy, A.A. Hazza, M.M. El-Meligy, Synthesis and in vitro evaluation of some novel benzofuran derivatives as potential antiHIV-1, anticancer, and antimicrobial agents, Arch. Pharm. Res., 29 (2006) 16-25.
• M.M. Mohamed, A.K. Khalil, E.M. Abbass, A.M. ElNaggar, Design, Synthesis of New Pyrimidine Derivatives as Anticancer and Antimicrobial Agents, Synthetic Commun., 47 (2017) 1441-1457.