Synthesis of New Bicyclic Hydroxamic Acids with Cytotoxic Activity
DOI:
https://doi.org/10.29356/jmcs.v61i4.467Keywords:
Hydroxamic acids, Michael addition, nitro group rearrangement, cytotoxic activityAbstract
Six new bicyclic hydroxamic acids were synthesized through an uncommon nitro group rearrangement between β-nitrostyrenes and dimedone. The structures of all the new synthesized compounds were confirmed using a combination of FTIR, 1H NMR, 13C NMR and mass spectral data. Likewise, the cytotoxic activity of the obtained products was evaluated in six different cancer cell lines. Two compounds showed significant potency on two cancer cell lines with IC50 between 9.31±0.1 and 23.38±0.9 μM.Downloads
References
Del Prete, G. Q.; Shoemaker, R.; Oswald, K.; Lara, A.; Trubey, C. M.; Fast, R.; Schneider, D. K.; Kiser, R.; Coalter, V.; Wiles, A.; Wiles, R.; Freemire, B.; Keele, B. F.; Estes, J. D.; Quiñones, O. A.; Smedley, J.; Macallister, R.; Sanchez, R. I.; Wai, J. S.; Tan, C. M.; Alvord, W. G.; Hazuda, D. J.; Piatak, M. Jr.; Lifson, J. D. Antimicrob. Agents Chemother. 2014, 58, 6790.
Yadav, R.; Murthy, R. V.; Kikkeri, R. Chembiochem. 2015, 16, 1448.
Domingo, J. L. Reprod. Toxicol. 1998, 12, 499.
Cabantchik, Z. I. Parasitol. Today. 1995,11, 74.
Igeta, K.; Tobbeto, K.; Saiki, I.; Odake, S.; Fujisawa, T.; Matsuo, T.; Oku, T. PCT Int. App. WO 003703, 2000.
AndaloussI, M.; Lindh, M.; Björkelid, C; Suresh, S.; Wieckowska, A.; Iyer, H.; Karlén, A.; Larhed, M. Bioorg. Med. Chem. Lett. 2011, 21, 5403.
Finnin, M. S; Donigian, J. R.; Cohen, A.; Richon, V. M.; Rifkind, R. A.; Marks, P. A.; Breslow, R.; Pavletich, N. P. Nature 1999, 401, 188.
Roberts, K. P.; Iyer, R. A.; Prasad, G.; Liu, L. T.; Lind, R. E.; Hanna,
P. E. Prostate. 1998, 34, 92.
Joshi, B.; Li, L.; Taffe, B. G.; Zhu, Z.; Wahl, S.; Tian, H.; Ben-Josef,
E.; Taylor, J. D.; Porter, A. T.; Tang, D. G. Cancer Res. 1999, 59, 4343.
Butler, L. M.; Agus, D. B.; Scher, H. I.; Higgins, B.; Rose, A.; Cordon-Cardo, C.; Thaler, H. T.; Rifkind, R. A.; Marks, P. A.; Richon, V. M. Cancer Res. 2000, 60, 5165.
Cheng, P.; Chen, J. J.; Huang, N.; Wang, R. R.; Zheng, Y. T.; Liang, Y. Z. Molecules. 2009, 14, 3176.
Pathe, G. K.; Ahmed, N. Tetrahedron Lett. 2015, 56, 6202.
Kumar, M. S.; Rajanna, K. C.; Reddy, K. R.; Venkateswarlu, M.; Venkanna, P. Synth. Commun. 2013, 43, 2672.
Özdemir, H. S.; ?ahin, E.; Çakici, M.; Kiliç, H. Tetrahedron. 2015, 71, 2882.
Larson, H.O.; Ooi, T. C.; Siu, A. K. Q.; Hollenbeak, K. H.; Cue, F. L. Tetrahedron. 1969, 25, 4005.
Tehrani, M. H. H; Farnia, M.; Nazer, M. S. Iran. J. Pharm. Res. 2003, 2, 1.
Basel, Y.; Hassner, A. Synthesis. 1997, 309.
Thomas-Mendivil, E.; Suárez, F. J.; Diez, J.; Cadierno, V. Chem. Commun. 2014, 50, 9661.
Ishikawa, T.; Miyahara, T.; Asakura, M.; Higuchi, S.; Miyauchi, Y.; Saito, S. Org. Lett. 2005, 7, 1211.
The synthesis of compound 5 was carried out starting from styrene which reacts with Br2 in CCl4 at room temperature to give (1,2-dibromoethyl) benzene. The dibromo derivative reacts first with NaN3 at room temperature and then with NaOH solution at 10 °C, both reactions in DMSO to give (1-azidoethenyl)benzene. Hortmann, A. G.; Robertson, D. A.; Gillard, B. K. J. Org. Chem. 1972, 37, 322. Afterwards, the pyrolysis of the former product at 150 °C in CH2Cl2 in a high pressure stainless steel reactor with hermetic seal, gives the corresponding 2H-azirine. Timén, Å. S.; Risberg, E.; Somfai, P. Tetrahedron Lett. 2003, 44, 5339. Treatment of the azirine with dimedone in acetone and the Ni(acac)2 as the catalyst at 35-40 °C for 15 min, then 3 h at room temperature leads to the desired compound 5. Dos Santos Fihlo, P. F.; Schuchardt, U. Angew. Chem. Int. Ed. Engl. 1977, 16, 647.
Skehan, P.; Storeng, R.; Scudiero, D.; Monks, A.; McMahon, J.; Vistica, D.; Warren, J. T.; Bokesch, H.; Kenney, S.; Boyd, M. R. J. Natl. Cancer Inst. 1990, 82, 1107.
Downloads
Published
Issue
Section
License
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
