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.
authors.affiliation: Laboratory for Drug Design and Synthesis, Centre for Chemical and Pharmaceutical Sciences, Central University of Punjab, 151 001 Bathinda, India.
authors.forename: Arvind
authors.initials: A
authors.lastname: Negi
authors.affiliation: Laboratory for Drug Design and Synthesis, Centre for Chemical and Pharmaceutical Sciences, Central University of Punjab, 151 001 Bathinda, India.
authors.forename: Jimi Marin
authors.initials: JM
authors.lastname: Alex
authors.affiliation: Department of Pharmaceutical Technology (Biotechnology), National Institute of Pharmaceutical Education and Research (NIPER), Mohali, S.A.S. Nagar, Sec 67, 160 062 Punjab, India.
authors.forename: Suyog M
authors.initials: SM
authors.lastname: Amrutkar
authors.affiliation: Department of Pharmaceutical Technology (Biotechnology), National Institute of Pharmaceutical Education and Research (NIPER), Mohali, S.A.S. Nagar, Sec 67, 160 062 Punjab, India.
authors.forename: Ashish T
authors.initials: AT
authors.lastname: Baviskar
authors.affiliation: Laboratory for Drug Design and Synthesis, Centre for Chemical and Pharmaceutical Sciences, Central University of Punjab, 151 001 Bathinda, India.
authors.forename: Gaurav
authors.initials: G
authors.lastname: Joshi
authors.affiliation: Centre for Genetic Diseases and Molecular Medicine, Central University of Punjab, 151 001 Bathinda, India.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Singh
authors.affiliation: Department of Pharmaceutical Technology (Biotechnology), National Institute of Pharmaceutical Education and Research (NIPER), Mohali, S.A.S. Nagar, Sec 67, 160 062 Punjab, India.
authors.forename: Uttam C
authors.initials: UC
authors.lastname: Banerjee
authors.affiliation: Laboratory for Drug Design and Synthesis, Centre for Chemical and Pharmaceutical Sciences, Central University of Punjab, 151 001 Bathinda, India. Electronic address: raj.khunger@gmail.com.
authors.forename: Raj
authors.initials: R
authors.lastname: Kumar
mesh_terms: D000951:Antigens, Neoplasm; D017209:Apoptosis; D049109:Cell Proliferation; D004250:DNA Topoisomerases, Type II; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D007093:Imidazoles / Q000378:metabolism*; D008872:Microwaves; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D059005:Topoisomerase II Inhibitors / Q000494:pharmacology*
chemical_list: D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D007093:Imidazoles; D059005:Topoisomerase II Inhibitors; C029899:imidazole; D004250:DNA Topoisomerases, Type II
keywords: Anticancer activity; Antioxidant activity; Imine/amide–imidazole; Molecular modeling; Topoisomerase inhibition