Imine/amide-imidazole conjugates derived from 5-amino-4-cyano-N1-substituted benzyl imidazole: Microwave-assisted synthesis and anticancer activity via selective topoisomerase-II-α inhibition

Arvind Negi; Jimi Marin Alex; Suyog M. Amrutkar; Ashish T. Baviskar; Gaurav Joshi; Sandeep Singh; Uttam C. Banerjee; Raj Kumar

doi:10.1016/j.bmc.2015.07.020

Imine/amide-imidazole conjugates derived from 5-amino-4-cyano-N1-substituted benzyl imidazole: Microwave-assisted synthesis and anticancer activity via selective topoisomerase-II-α inhibition

Arvind Negi, Jimi Marin Alex, Suyog M. Amrutkar, Ashish T. Baviskar, Gaurav Joshi, Sandeep Singh, Uttam C. Banerjee, Raj Kumar

Research output: Contribution to journal › Article › peer-review

51 Scopus citations

Abstract

Microwave-accelerated synthesis and anticancer activity of novel imine/amide-imidazole conjugates derived from 5-amino-4-cyano-N1-substituted benzyl imidazole against a panel of seven cancer cell lines are reported for the first time. Compounds ARK-4, 10 and 12 in the series show promising in vitro anti proliferative activity with low micromolar IC₅₀ values against A-459 (lung), Hep-G2 (liver) and H-460 (liver) cancer cell lines. Compounds caused the increase in ROS levels as well as mitochondrial membrane depolarization, which might induce apoptosis. Further, mechanistic interventions on biological and molecular modeling data supported that compounds inhibited topoisomerase-II selectively.

Original language	English (US)
Pages (from-to)	5654-5661
Number of pages	8
Journal	Bioorganic and Medicinal Chemistry
Volume	23
Issue number	17
DOIs	https://doi.org/10.1016/j.bmc.2015.07.020
State	Published - May 26 2015
Externally published	Yes

Keywords

Anticancer activity
Antioxidant activity
Imine/amide-imidazole
Molecular modeling
Topoisomerase inhibition

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmc.2015.07.020

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Negi, A., Alex, J. M., Amrutkar, S. M., Baviskar, A. T., Joshi, G., Singh, S., Banerjee, U. C., & Kumar, R. (2015). Imine/amide-imidazole conjugates derived from 5-amino-4-cyano-N1-substituted benzyl imidazole: Microwave-assisted synthesis and anticancer activity via selective topoisomerase-II-α inhibition. Bioorganic and Medicinal Chemistry, 23(17), 5654-5661. https://doi.org/10.1016/j.bmc.2015.07.020

Imine/amide-imidazole conjugates derived from 5-amino-4-cyano-N1-substituted benzyl imidazole: Microwave-assisted synthesis and anticancer activity via selective topoisomerase-II-α inhibition. / Negi, Arvind; Alex, Jimi Marin; Amrutkar, Suyog M. et al.
In: Bioorganic and Medicinal Chemistry, Vol. 23, No. 17, 26.05.2015, p. 5654-5661.

Research output: Contribution to journal › Article › peer-review

Negi, A, Alex, JM, Amrutkar, SM, Baviskar, AT, Joshi, G, Singh, S, Banerjee, UC & Kumar, R 2015, 'Imine/amide-imidazole conjugates derived from 5-amino-4-cyano-N1-substituted benzyl imidazole: Microwave-assisted synthesis and anticancer activity via selective topoisomerase-II-α inhibition', Bioorganic and Medicinal Chemistry, vol. 23, no. 17, pp. 5654-5661. https://doi.org/10.1016/j.bmc.2015.07.020

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title = "Imine/amide-imidazole conjugates derived from 5-amino-4-cyano-N1-substituted benzyl imidazole: Microwave-assisted synthesis and anticancer activity via selective topoisomerase-II-α inhibition",

abstract = "Microwave-accelerated synthesis and anticancer activity of novel imine/amide-imidazole conjugates derived from 5-amino-4-cyano-N1-substituted benzyl imidazole against a panel of seven cancer cell lines are reported for the first time. Compounds ARK-4, 10 and 12 in the series show promising in vitro anti proliferative activity with low micromolar IC50 values against A-459 (lung), Hep-G2 (liver) and H-460 (liver) cancer cell lines. Compounds caused the increase in ROS levels as well as mitochondrial membrane depolarization, which might induce apoptosis. Further, mechanistic interventions on biological and molecular modeling data supported that compounds inhibited topoisomerase-II selectively.",

keywords = "Anticancer activity, Antioxidant activity, Imine/amide-imidazole, Molecular modeling, Topoisomerase inhibition",

author = "Arvind Negi and Alex, {Jimi Marin} and Amrutkar, {Suyog M.} and Baviskar, {Ashish T.} and Gaurav Joshi and Sandeep Singh and Banerjee, {Uttam C.} and Raj Kumar",

note = "Funding Information: R.K. and S.S. thank DST and UGC , New Delhi, India for the financial assistance (F. No. SR/FT/CS-71/2011 ) and F.30-13/2013(BSR) , respectively. S.M.A., A.T.B. and U.C.B. gratefully acknowledge the financial aid from DBT Government of India , New Delhi to carry out hTopoI and hTopoII activity evaluation studies. J.M.A. and R.K. also thank Maulana Azad National Fellowship (F1-17.1/2013-14/MANF-2013-14-CHR-DEL-27187) for the same. Encouragement and support from Prof. P. Ramarao, Dean, and Prof. R.K. Kohli, Vice Chancellor Central University of Punjab, is gratefully acknowledged. Publisher Copyright: {\textcopyright} 2015 Elsevier Ltd. All rights reserved.",

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AU - Negi, Arvind

AU - Alex, Jimi Marin

AU - Amrutkar, Suyog M.

AU - Baviskar, Ashish T.

AU - Joshi, Gaurav

AU - Singh, Sandeep

AU - Banerjee, Uttam C.

AU - Kumar, Raj

N1 - Funding Information: R.K. and S.S. thank DST and UGC , New Delhi, India for the financial assistance (F. No. SR/FT/CS-71/2011 ) and F.30-13/2013(BSR) , respectively. S.M.A., A.T.B. and U.C.B. gratefully acknowledge the financial aid from DBT Government of India , New Delhi to carry out hTopoI and hTopoII activity evaluation studies. J.M.A. and R.K. also thank Maulana Azad National Fellowship (F1-17.1/2013-14/MANF-2013-14-CHR-DEL-27187) for the same. Encouragement and support from Prof. P. Ramarao, Dean, and Prof. R.K. Kohli, Vice Chancellor Central University of Punjab, is gratefully acknowledged. Publisher Copyright: © 2015 Elsevier Ltd. All rights reserved.

PY - 2015/5/26

Y1 - 2015/5/26

N2 - Microwave-accelerated synthesis and anticancer activity of novel imine/amide-imidazole conjugates derived from 5-amino-4-cyano-N1-substituted benzyl imidazole against a panel of seven cancer cell lines are reported for the first time. Compounds ARK-4, 10 and 12 in the series show promising in vitro anti proliferative activity with low micromolar IC50 values against A-459 (lung), Hep-G2 (liver) and H-460 (liver) cancer cell lines. Compounds caused the increase in ROS levels as well as mitochondrial membrane depolarization, which might induce apoptosis. Further, mechanistic interventions on biological and molecular modeling data supported that compounds inhibited topoisomerase-II selectively.

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Imine/amide-imidazole conjugates derived from 5-amino-4-cyano-N1-substituted benzyl imidazole: Microwave-assisted synthesis and anticancer activity via selective topoisomerase-II-α inhibition

Abstract

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