Synthesis, docking and biological evaluation of isoquinolonic acid derivatives

Abstract

A series of isoquinolonic acid derivatives(4a–4o) was synthesized via one-pot synthesis for their anti-tumor activity. The structures of all the targeted compounds were confirmed by ¹H nuclear magnetic resonance (¹H NMR) spectrometry and mass spectrometry(MS). The anti-tumor activities of compounds 4a–4o against MG63(human osteosarcoma cells) and B16-F10(mouse melanoma cells) were examined. To evaluate the antitumor effect of the as-synthe sized compounds, we compared the half maximal inhibitory concentration(IC₅₀) of compounds 4a–4o to that of camptothecin(CPT) which appeared to be active against a broad range of human cancers. Among all the compounds, compound 4l shows the most potent biological activity against MG63 cells[IC₅₀=(2.16±0.26) μmol/L]_and B16-F10 cells[IC₅₀=(6.95±0.24) μmol/L], thus providing useful information for the antitumor activity and potential practical use of isoquinolonic acid compounds. In addition, we screened out an efficient compound(4l) that shows potential inhibit activity against Topoisomerase I(Topo I) by docking simulation.

Keywords

Isoquinolonic acid compound / Antitumor activity / Molecular docking

References

[1] Cushman M, Chen J. J. Org. Chem., 1987, 52: 1517.

[2] Fodor L, Szabo J, Bernath G, Sohar P, Maclean D B, Smith R W, Ninomiya I, Naito T. J. Heterocyclic Chem., 1989, 26: 333.

[3] Cushman M, Cheng L. J. Org. Chem., 1978, 43: 286.

[4] Bonnaud B, Carlessi A, Bigg D C H. J. Heterocyclic Chem., 1993, 30: 257.

[5] Cushman M, Abbaspour A, Gupta Y P. J. Am. Chem. Soc., 1983, 105: 2873.

[6] Povarov L S. Russ. Chem. Rev., 1967, 36: 656.

[7] Yamada N, Kadowaki S, Takahashi S. Biochem. Pharmacol., 1992, 4: 1211.

[8] Faber K, Stueckler H, Kappe T. J. Heterocyclic Chem., 1984, 21: 1177.

[9] Johnson J V, Rauckman B S, Baccanari D P, Roth B. J. Med. Chem., 1989, 32: 1942.

[10] Katherine E P, Maris A C, Andrew E M. J. Med. Chem., 2011, 54: 4937.

[11] Cushman M, Gentry J, Dekow F W. J. Org. Chem., 1977, 42: 1111.

[12] Mohammadi M H, Mohammadi A A. Synthetic Communications, 2011, 41: 523.

[13] Yu N F, Bourel L, Deprez B, Gesquiere J C. Tetrahedron Lett., 1998, 39: 829.

[14] Yadav J S, Reddy B V S, Reddy K S. Tetrahedron, 2003, 59: 5333.

[15] Azizian J, Mohammadi A A, Karimi A R, Mohammadizadeh M R. J. Org. Chem., 2005, 70: 350.

[16] Azizian J, Mohammadi A A, Soleimani E, Karimi A R, Mohammadizadeh M R. J. Heterocyclic Chem., 2006, 43: 187.

[17] Yadav J S, Reddy B V S, Reddy A R. Synthesis-stuttgart, 2007, 20: 3191.

[18] Pommier Y, Pourquier P, Yi F, Strumberg D. Biochimica et Biophysica Acta, 1998, 1400: 83.

[19] Grummitt O, Egan R, Buck A. Organic Syntheses, 1949, 29: 49.

[20] Wang L M L J J, Tian H, Tian C T, Sun J. Adv. Synth. Catal., 2005, 347: 689.

[21] Ma Z Y, Zhang X Y, Li C N, Zheng Y J, Wang S K, He Y. Chem. J. Chinese Universities, 2011, 27(5): 787.

[22] Liu D, Zhu X J, Jiang M, Chen H, Lan S P. Chem. J. Chinese Universities, 2012, 33(10): 2249.

[23] Wall M E, Wani M C, Cook C E, Palmer K H, Mcphail A T, Sim G A. J. Am. Chem. Soc., 1966, 88: 3888.

[24] Pommier Y. Nat. Rev. Cancer, 2006, 6: 789.