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Letters in Organic Chemistry

Editor-in-Chief

ISSN (Print): 1570-1786
ISSN (Online): 1875-6255

Research Article

Novel Pyrazolyl Benzoxazole Conjugates: Design, Synthesis, Molecular Docking Studies and in vitro Anticancer Activities

Author(s): Arunkumar Thiriveedhi*, Ratnakaram Venkata Nadh, Navuluri Srinivasu and Narayana Murthy Ganta

Volume 16, Issue 8, 2019

Page: [619 - 626] Pages: 8

DOI: 10.2174/1570178615666181022141919

Price: $65

Abstract

Nowadays, hybrid drugs have gained a significant role in the treatment of different health problems. Most of the hybrid molecules with different heterocyclic moieties were proved to be potent anti-tumor agents in cancer chemotherapy. Hence, the present study is aimed at the evaluation of in vitro anticancer activity of novel hybrid molecules (pyrazolyl benzoxazole conjugates) and to investigate their anticancer activity by molecular docking studies. Designed, synthesized and characterized the novel pyrazolyl benzoxazole conjugates. Anticancer activity of these compounds was determined by SRB assay. Then molecular docking studies were carried out against proto-oncogene tyrosine-protein kinase (ATP-Src, PDB: 2BDF), a putative target for cancer. All the synthesized compound derivatives were evaluated against MCF-7, KB, Hop62 and A549 cancer cell lines. Compounds 9b and 9c exhibited excellent anticancer activities with GI50 values of <0.1 µM against MCF-7 and A549 cell lines. Compound 9e exhibited good antitumor activity on MCF-7 and A-549 with GI50 values of 0.12 µM and 0.19 µM respectively. Compound 9g showed better anticancer activity on A-549 cancer cell line with GI50 of 0.34 µM. The two-hybrid molecules 9b and 9c are found to be comparably potent with the standard drug doxorubicin and may act as drug lead compounds in medicinal chemistry aspect. The present docking investigation proved that having benzoxazole of compound 9c at the position of benzofuran of reference compound (N-acetyl pyrazoline derivative) might be valid for contributing to anti-cancer activity.

Keywords: Benzoxazole, pyrazole, doxorubicin, anticancer activity, molecular docking studies, chemotherapy.

Graphical Abstract

[1]
[2]
The top 10 causes of death Fact sheet N°310". WHO. May 2014. 10 June 2014.
[3]
Takiar, R.; Nadiyal, D.; Nandakumar, A. Asian Pac. J. Cancer Prev., 2010, 11, 1045-1049.
[4]
Ali, R.; Mirza, Z.; Ashraf, G.M.; Kamal, M.A.; Ansari, S.A.; Damanhouri, G.A.; Abuzenadah, A.M.; Chaudhary, A.G.; Sheikh, I.A. Anticancer Res., 2012, 32, 2999-3005.
[5]
McCubrey, J.A.; Steelman, L.S.; Abrams, S.L.; Lee, J.T.; Chang, F.; Bertrand, F.E.; Navolanic, P.M.; Terrian, D.M.; Franklin, R.A.; D’Assoro, A.B.; Salishbury, J.L.; Mazzarino, M.C.; Stivala, F.; Libra, M. Adv. Enzym Regul., 2006, 46, 249-279.
[6]
Sreedhar, A.S.; Csermely, P. Pharmacol. Ther., 2004, 101, 227-257.
[7]
Kumar, A.; Srivastava, K.; Kumar, S.R.; Puri, S.K.; Chauhan, P.M. Bioorg. Med. Chem. Lett., 2010, 20(23), 7059-7063.
[8]
Teiten, M.H.; Dicato, M.; Diederich, M. Molecules, 2014, 19(12), 20839-20863.
[9]
Christiaans, J.A.M.; Timmerman, H. Eur. J. Med. Chem., 1996, 4, 1-22.
[10]
Saadeh, H.A.; Mosleh, I.M.; Mubarak, M.S. Molecules, 1996, 14(4), 1483-1494.
[11]
Mukhopadhyay, J.; Das, K.; Ismail, S.; Koppstein, D.; Jang, M.; Hudson, B.; Sarafianos, S.; Tuske, S.; Patel, J.; Jansen, R.; Irschik, H. Cell, 2008, 135(2), 295-307.
[12]
Prokopiou, E.M.; Ryder, S.A.; Walsh, J.J. Angiogenesis, 2013, 16(3), 503-524.
[13]
Breen, E.C.; Walsh, J.J. Curr. Med. Chem., 2010, 17(7), 609-639.
[14]
Suresh, G.; Nadh, R.V.; Srinivasu, N.; Durgaprasad, Y. Lett. Org. Chem., 2018, 12, 1070-1077.
[15]
Thiriveedhi, A.; Nadh, R.V.; Srinivasu, N.; Kaushal, K. Lett. Drug Design. Discov., 2018, 15(7), 757-765.
[16]
Thiriveedhi, A.; Venkata, N.R.; Srinivasu, N.; Kaushal, K. Lett. Drug Design. Discov., 2018, 15, 576-582.
[17]
Iverson, N.M.; Barone, P.W.; Shandell, M.; Trudel, L.J.; Sen, S.; Sen, F.; Ivanov, V.; Atolia, E.; Farias, E.; McNicholas, T.P.; Reuel, N. Nat. Nanotechnol., 2013, 8(11), 873.
[18]
Sen, F.; Boghossian, A.A.; Sen, S.; Ulissi, Z.W.; Zhang, J.; Strano, M.S. ACS Nano, 2012, 6(12), 10632-10645.
[19]
Ulissi, Z.W.; Sen, F.; Gong, X.; Sen, S.; Iverson, N.; Boghossian, A.A.; Godoy, L.C.; Wogan, G.N.; Mukhopadhyay, D.; Strano, M.S. Nano Lett., 2014, 14(8), 4887-4894.
[20]
Zhang, J.; Landry, M.P.; Barone, P.W.; Kim, J.H.; Lin, S.; Ulissi, Z.W.; Lin, D.; Mu, B.; Boghossian, A.A.; Hilmer, A.J.; Rwei, A. Nat. Nanotechnol., 2013, 8(12), 959.
[21]
Sahin, B.; Aygun, A.; Gunduz, H.; Sahin, K.; Demir, E.; Akocak, S.; Sen, F. Colloids Surf. B Biointerf, 2018, 163, 119-124.
[22]
Sahin, B.; Demir, E.; Aygun, A.; Gunduz, H.; Sen, F. J. Biotechnol., 2017, 260, 79-83.
[23]
Hatti, I.; Sreenivasulu, R.; Jadav, S.S.; Jayaprakash, V.; Kumar, C.G.; Raju, R.R. Med. Chem. Res., 2015, 24, 3305-3313.
[24]
Madhavi, S.; Sreenivasulu, R.; Ansari, Y.; Ahsan, M.J. Raju. R.R. Lett. Org. Chem., 2016, 13, 682-692.
[25]
Madhavi, S.; Sreenivasulu, R.; Jyotsna, Y.; Raju, R.R. Saudi Pharm. J., 2017, 25, 275-279.
[26]
Ahsan, M.J.; Choudhary, K.; Jadav, S.S.; Yasmin, S.; Ansari, M.Y.; Sreenivasulu, R. Med. Chem. Res., 2015, 24, 4166-4180.
[27]
Rai, U.S.; Isloor, A.M.; Shetty, P.; Pai, K.S.R.; Fun, H.K. Arab. J. Chem., 2015, 8, 317-321.
[28]
Salgin-Goksen, U.; Gokhan-Kelekci, N.; Goktas, O.; Koysal, Y.; Kilic, E.; Isik, S.; Aktay, G.; Ozalp, M. Bioorg. Med. Chem., 2007, 15, 5738-5751.
[29]
Selvam, T.P.; Kumar, P.V.; Saravanan, G.; Prakash, C.R. J. Saudi Chem. Soc., 2014, 18, 1015-1021.
[30]
Rani, M.; Yusuf, M.; Khan, S.A.; Sahota, P.P.; Pandove, G. Arab. J. Chem., 2015, 8, 174-180.
[31]
Jadav, S.S.; Sinha, B.N.; Pastorino, B.; deLamballerie, X.; Hilgenfeld, R.; Jayaprakash, V. Lett. Drug Des. Discov., 2015, 12, 292-301.
[32]
Satasia, S.P.; Kalaria, P.N.; Raval, D.K. Org. Biomol. Chem., 2014, 12, 1751-1758.
[33]
Gunasekaran, P.; Perumal, S.; Yogeeswari, P.; Sriram, D. Eur. J. Med. Chem., 2011, 46, 4530-4536.
[34]
Mesa, R.A. Drugs, 2010, 13, 394-403.
[35]
Zou, H.Y.; Li, Q.; Lee, J.H.; Arango, M.E.; McDonnell, S.R.; Yamazaki, S. Cancer Res., 2007, 67, 4408-4417.
[36]
Kumar, D.; Jacob, M.R.; Reynolds, M.B.; Kerwin, S.M. Bioorg. Med. Chem., 2002, 10, 3997-4004.
[37]
Murty, M.S.R.; Ram, K.R.; Rao, R.V.; Yadav, J.S.; Rao, J.V.; Cheriyan, V.T.; Anto, R.J. Med. Chem. Res., 2012, 20, 576-586.
[38]
Oksuzoglu, E.; Tekiner-Gulbas, B.; Alper, S.; Temiz-Arpaci, O.; Ertan, T.; Yildiz, I.; Diril, N.; Sener-Aki, E.; Yalcin, I. J. Enzyme Inhib. Med. Chem., 2008, 23, 37-42.
[39]
O’Donnell, C.J.; Rogers, B.N.; Bronk, B.S.; Bryce, D.K.; Coe, J.W.; Cook, K.K.; Duplantier, A.J.; Evrard, E.; Hajos, M.; Hoffmann, W.E.; Hurst, R.S.; Aklad, N.; Mather, R.J.; McLean, S.; Nedza, F.M. ONeill, B.T.; Peng, L.; Qian, W.; Rottas, M.M.; Sands, S.B.; Zhang, L. J. Med. Chem., 2010, 53, 1222-1237.
[40]
Cheung, M.; Harris, P.; Hasegawa, M.; Ida, S.; Kano, K.; Nishigaki, N. WO 02/44156A2 2002.
[41]
Clark, D.; Eastwood, P.; Harris, N.; McCarthy, C.; Morley, A.; Pickett, S. PCT WO 00/49005 2000.
[42]
Muller, P.; Huranus, R.; Maier, R.; Mark, M.; Eisele, S.; Budzinski, R.; Thomas, L.; Hallermayer, G. US Patent US 5919807 1999.
[43]
Sato, Y. Yamada, M.; Kobayashi, K.; Iwamatsu, K.; Konno, F.; Shudo. K EP 806419 A1 1997.
[44]
Surleraux, D.; Vendeville, S.; Verschueren, W.; DeBethune, M.; DeKock, H.; Tahri, A. WO 02/092595A1 2002.
[45]
Laibekman, A.; Jantzen, H.M.; Conley, L.; Fretto, L.; Scarborough, R. US 6667306B1 2003.
[46]
Skehn, P.; Storeng, R.; Scudiero, A.; Monks, J.; McMohan, D.; Vistica, D.; Jonathan, W.T.; Bokesch, H.; Kenney, S.; Boyd, R.M. J. Natl. Cancer Inst., 1990, 82, 1107-1112.
[47]
El-Karim, S.S.A.; Anwar, M.M.; Mohamed, N.A.; Nasr, T.; Elseginy, S.A. Bioorg. Chem., 2015, 63, 1-12.
[48]
Dalgarno, D.; Stehle, T.; Narula, S.; Schelling, P.; Schravendijk, M.R.V.; Adams, S.; Andrade, L.; Keats, J.; Ram, M.; Jin, L.; Grossman, T.; MacNeil, I.; Metcalf, C.; Shakespeare, W.; Wang, Y.; Keenam, T.; Sundaramoorthi, R.; Bohacek, R.; Weigele, M.; Sawyer, T. Chem. Biol. Drug Des., 2006, 67, 46-57.
[49]
Friesner, R.A.; Banks, J.L.; Murphy, R.B.; Halgren, T.A.; Klicic, J.J.; Mainz, D.T.; Repasky, M.P.; Knoll, E.H.; Shelley, M.; Perry, J.K.; Shaw, D.E.; Francis, P.; Shenkin, P.S. J. Med. Chem., 2004, 47, 1739-1749.

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