Synthesis and Anticancer Evaluation of Bis Furfurylidene-4-piperidone Analog of 5-Fluorouracil

Rahul L. Jadhav; Pravin K. Pawar; Manisha V. Patil

doi:10.14233/ajchem.2017.20487

Issue

Vol. 29 No. 6 (2017): Vol 29 Issue 6

Issue Published : April 10, 2017

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

Synthesis and Anticancer Evaluation of Bis Furfurylidene-4-piperidone Analog of 5-Fluorouracil

https://doi.org/10.14233/ajchem.2017.20487

Rahul L. Jadhav

Department of Pharmaceutical Chemistry, Gourishankar Institute of Pharmaceutical Education and Research, Limb, Satara-415 015, India

Pravin K. Pawar

Department of Pharmaceutical Chemistry, Gourishankar Institute of Pharmaceutical Education and Research, Limb, Satara-415 015, India

Manisha V. Patil

Adarsh College of Pharmacy, Vita-415 311, India

Corresponding Author(s) : Rahul L. Jadhav

rahuljadhav_25@rediffmail.com

Asian Journal of Chemistry, Vol. 29 No. 6 (2017): Vol 29 Issue 6
Article Published : April 9, 2017

Abstract

5-Fluorouracil (5-FU) displayed several side effects due to its nonspecific cytotoxicity for tumour cells. In order to overcome these disadvantages, numerous modifications of the 5-fluorouracil structure have been performed. In the present study, bis furfurylidene-4-piperidone substituted 5-flurouracil derivative is prepared and evaluated against various cancer cells. The resultant derivative is characterized by spectral data. This compound having 1,5-diaryl-3-oxo-1,4-pentadinenyl pharmacophore which interact with cellular thiols and produces cytotoxic activity whereas 5-flurouracil part showed anticancer activity by interacting with nucleic acid. The resulting synthesized compound has been screened for in vitro cytotoxic property by SRB assay method against breast and colon cancer cell lines. The results indicate that, this compound showed equipotent cytotoxicity against human breast cell lines as compared to standard, 5-flurouracil and doxorubicin. Acute toxicity was determined by OECD-423 guidelines. In vivo anticancer activity was evaluated in Swiss albino mice bearing Ehrlich Ascites Carcinoma (EAC). This compound showed significant anticancer activity against Ehrlich Ascites Carcinoma in Swiss albino mice. This study revealed the potentiality of this molecule for further development as anticancer agents.

Keywords

4-Piperidones 5-Fluorouracil derivatives Cytotoxic agents a,b-unsaturated ketones Alkylating agents and Anticancer agents

Jadhav, R. L., Pawar, P. K., & Patil, M. V. (2017). Synthesis and Anticancer Evaluation of Bis Furfurylidene-4-piperidone Analog of 5-Fluorouracil. Asian Journal of Chemistry, 29(6), 1337–1340. https://doi.org/10.14233/ajchem.2017.20487

Download Citation

References

P.C. Wang, F. Wang, P. Li, Z. Hu, Y. Shan and J. Zhang, Curr. Med. Chem., 18, 4538 (2011); https://doi.org/10.2174/092986711797287584.
R.B. Silverman, The Organic Chemistry of Drug Design and Drug Action, Academic Press, Inc, San Diego, pp. 220-222 (1992).
A. Baluja, A.M. Municio and S. Vega, Chem. Ind., 2053 (1964).
J.R. Dimmock, S.K. Raghavan, B.M. Logan and G.E. Bigam, Eur. J. Med. Chem., 18, 248 (1983).
J.A. Benvenuto, T.H. Connor, D.K. Monteith, J.L. Laidlaw, S.C. Adams, T.S. Matney and J.C. Theiss, J. Pharm. Sci., 82, 988 (1993); https://doi.org/10.1002/jps.2600821007.
J.R. Dimmock, P. Kumar, A.J. Nazarali, N.L. Motaganahalli, T.P. Kowalchuk, M.A. Beazely, J. Wilson Quail, E.O. Oloo, T.M. Allen, J. Szydlowski, E. DeClercq and J. Balzarini, Eur. J. Med. Chem., 35, 967 (2000); https://doi.org/10.1016/S0223-5234(00)01173-9.
R.L. Jadhav and C.S. Magdum, Asian J. Chem., 24, 3263 (2012).
J.R. Dimmock, M.P. Padmanilayam, G.A. Zello, K.H. Nienaber, T.M. Allen, C.L. Santos, E. De Clercq, J. Balzarini, E.K. Manavathu and J.P. Stables, Eur. J. Med. Chem., 38, 169 (2003); https://doi.org/10.1016/S0223-5234(02)01444-7.
J.R. Dimmock, M.P. Padmanilayam, R.N. Puthucode, A.J. Nazarali, N.L. Motaganahalli, G.A. Zello, J.W. Quail, E.O. Oloo, H.-B. Kraatz, J.S. Prisciak, T.M. Allen, C.L. Santos, J. Balzarini, E. De Clercq and E.K. Manavathu, J. Med. Chem., 44, 586 (2001); https://doi.org/10.1021/jm0002580.
J.R. Dimmock, M.P. Padmanilyam, G.A. Zello, J. Wilson Quail, E.O. Oloo, J.S. Prisciak, H.-B. Kraatz, A. Cherkasov, J.S. Lee, T.M. Allen, C.L. Santos, E.K. Manavathu, E. De Clercq, J. Balzarini and J.P. Stables, Eur. J. Med. Chem., 37, 813 (2002); https://doi.org/10.1016/S0223-5234(02)01402-2.
J.L. Wike-Hooley, J. Haveman and H.S. Reinhold, Radiother. Oncol., 2, 343 (1984); https://doi.org/10.1016/S0167-8140(84)80077-8.
G.K. Balendiran, R. Dabur and D. Fraser, Cell Biochem. Funct., 22, 343 (2004); https://doi.org/10.1002/cbf.1149.
C. Garcia-Ruiz, M. Mari, A. Morales, A. Colell, E. Ardite and J.C. Fernandez-Checa, Hepatology, 32, 56 (2000); https://doi.org/10.1053/jhep.2000.8267.
M.L.P.S. van Iersel, J.-P.H.T.M. Ploemen, I. Struik, C. van Amersfoort, A.E. Keyzer, J.G. Schefferlie and P.J. van Bladeren, Chem. Biol. Interact., 102, 117 (1996); https://doi.org/10.1016/S0009-2797(96)03739-8.
P.J. O’Dwyer, F. LaCreta, S. Nash, P.W. Tinsley, R. Schilder, M.L. Clapper, K.D. Tew, L. Panting, S. Litwin and R.L. Comis, Cancer Res., 51, 6059 (1991).
R.L. Jadhav, C.S. Magdum and M.V. Patil, Arch. Pharm. Chem. life Sci., 347, 407 (2014); https://doi.org/10.1002/ardp.201300429.
P. Skehan, R. Storeng, D. Scudiero, A. Monks, J. McMahon, D. Vistica, J.T. Warren, H. Bokesch, S. Kenney and M.R. Boyd, J. Natl. Cancer Inst., 82, 1107 (1990); https://doi.org/10.1093/jnci/82.13.1107.
R.L. Jadhav and C.S. Magdum, J. Pharm. Res., 4, 3093 (2011).
OECD Guideline for Testing of Chemicals: 423, Acute Oral Toxicity –Acute Toxic Class Method (2001).
R.L. Jadhav and C.S. Magdum, Lat. Am. J. Pharm., 32, 135 (2013).
Y. Rajeshwar, M. Gupta and U.K. Mazumder, Iran. J. Pharmacol. Therap., 4, 46 (2005).
S.B. Prasad and A. Giri, Indian J. Exp. Biol., 32, 155 (1994).
B.D. Clarkson and J.H. Burchenal, Prog. Clin. Cancer, 1, 625 (1965).
V.E. Price and R.E. Greenfield, Adv. Cancer Res., 5, 199 (1958); https://doi.org/10.1016/S0065-230X(08)60413-3.
H.C. Hogland, Semin. Oncol., 9, 95 (1982).
L.D. Fenninger and G.B. Mider, Adv. Cancer Res., 2, 229 (1954); https://doi.org/10.1016/S0065-230X(08)60496-0

References

P.C. Wang, F. Wang, P. Li, Z. Hu, Y. Shan and J. Zhang, Curr. Med. Chem., 18, 4538 (2011); https://doi.org/10.2174/092986711797287584.

R.B. Silverman, The Organic Chemistry of Drug Design and Drug Action, Academic Press, Inc, San Diego, pp. 220-222 (1992).

A. Baluja, A.M. Municio and S. Vega, Chem. Ind., 2053 (1964).

J.R. Dimmock, S.K. Raghavan, B.M. Logan and G.E. Bigam, Eur. J. Med. Chem., 18, 248 (1983).

J.A. Benvenuto, T.H. Connor, D.K. Monteith, J.L. Laidlaw, S.C. Adams, T.S. Matney and J.C. Theiss, J. Pharm. Sci., 82, 988 (1993); https://doi.org/10.1002/jps.2600821007.

J.R. Dimmock, P. Kumar, A.J. Nazarali, N.L. Motaganahalli, T.P. Kowalchuk, M.A. Beazely, J. Wilson Quail, E.O. Oloo, T.M. Allen, J. Szydlowski, E. DeClercq and J. Balzarini, Eur. J. Med. Chem., 35, 967 (2000); https://doi.org/10.1016/S0223-5234(00)01173-9.

R.L. Jadhav and C.S. Magdum, Asian J. Chem., 24, 3263 (2012).

J.R. Dimmock, M.P. Padmanilayam, G.A. Zello, K.H. Nienaber, T.M. Allen, C.L. Santos, E. De Clercq, J. Balzarini, E.K. Manavathu and J.P. Stables, Eur. J. Med. Chem., 38, 169 (2003); https://doi.org/10.1016/S0223-5234(02)01444-7.

J.R. Dimmock, M.P. Padmanilayam, R.N. Puthucode, A.J. Nazarali, N.L. Motaganahalli, G.A. Zello, J.W. Quail, E.O. Oloo, H.-B. Kraatz, J.S. Prisciak, T.M. Allen, C.L. Santos, J. Balzarini, E. De Clercq and E.K. Manavathu, J. Med. Chem., 44, 586 (2001); https://doi.org/10.1021/jm0002580.

J.R. Dimmock, M.P. Padmanilyam, G.A. Zello, J. Wilson Quail, E.O. Oloo, J.S. Prisciak, H.-B. Kraatz, A. Cherkasov, J.S. Lee, T.M. Allen, C.L. Santos, E.K. Manavathu, E. De Clercq, J. Balzarini and J.P. Stables, Eur. J. Med. Chem., 37, 813 (2002); https://doi.org/10.1016/S0223-5234(02)01402-2.

J.L. Wike-Hooley, J. Haveman and H.S. Reinhold, Radiother. Oncol., 2, 343 (1984); https://doi.org/10.1016/S0167-8140(84)80077-8.

G.K. Balendiran, R. Dabur and D. Fraser, Cell Biochem. Funct., 22, 343 (2004); https://doi.org/10.1002/cbf.1149.

C. Garcia-Ruiz, M. Mari, A. Morales, A. Colell, E. Ardite and J.C. Fernandez-Checa, Hepatology, 32, 56 (2000); https://doi.org/10.1053/jhep.2000.8267.

M.L.P.S. van Iersel, J.-P.H.T.M. Ploemen, I. Struik, C. van Amersfoort, A.E. Keyzer, J.G. Schefferlie and P.J. van Bladeren, Chem. Biol. Interact., 102, 117 (1996); https://doi.org/10.1016/S0009-2797(96)03739-8.

P.J. O’Dwyer, F. LaCreta, S. Nash, P.W. Tinsley, R. Schilder, M.L. Clapper, K.D. Tew, L. Panting, S. Litwin and R.L. Comis, Cancer Res., 51, 6059 (1991).

R.L. Jadhav, C.S. Magdum and M.V. Patil, Arch. Pharm. Chem. life Sci., 347, 407 (2014); https://doi.org/10.1002/ardp.201300429.

P. Skehan, R. Storeng, D. Scudiero, A. Monks, J. McMahon, D. Vistica, J.T. Warren, H. Bokesch, S. Kenney and M.R. Boyd, J. Natl. Cancer Inst., 82, 1107 (1990); https://doi.org/10.1093/jnci/82.13.1107.

R.L. Jadhav and C.S. Magdum, J. Pharm. Res., 4, 3093 (2011).

OECD Guideline for Testing of Chemicals: 423, Acute Oral Toxicity –Acute Toxic Class Method (2001).

R.L. Jadhav and C.S. Magdum, Lat. Am. J. Pharm., 32, 135 (2013).

Y. Rajeshwar, M. Gupta and U.K. Mazumder, Iran. J. Pharmacol. Therap., 4, 46 (2005).

S.B. Prasad and A. Giri, Indian J. Exp. Biol., 32, 155 (1994).

B.D. Clarkson and J.H. Burchenal, Prog. Clin. Cancer, 1, 625 (1965).

V.E. Price and R.E. Greenfield, Adv. Cancer Res., 5, 199 (1958); https://doi.org/10.1016/S0065-230X(08)60413-3.

H.C. Hogland, Semin. Oncol., 9, 95 (1982).

L.D. Fenninger and G.B. Mider, Adv. Cancer Res., 2, 229 (1954); https://doi.org/10.1016/S0065-230X(08)60496-0

Issue

Vol. 29 No. 6 (2017): Vol 29 Issue 6

Synthesis and Anticancer Evaluation of Bis Furfurylidene-4-piperidone Analog of 5-Fluorouracil

Corresponding Author(s) : Rahul L. Jadhav

Abstract

Keywords

Full Article

Download Citation

References

Table Of Contents