Tumoricidal Potential of Novel Amino-1,10-phenanthroline Derived Imine Ligands: Chemical Preparation, Structure, and Biological Investigations
Kollur Shiva Prasad,
Renjith Raveendran Pillai,
Chandan Shivamallu,
Shashanka K. Prasad,
Anisha S. Jain,
Sushma Pradeep,
Stevan Armaković,
Sanja J. Armaković,
Chandrashekar Srinivasa,
Sharadadevi Kallimani,
Raghavendra G. Amachawadi,
Veena Malligere Ankegowda,
Najat Marraiki,
Abdallah M. Elgorban,
Asad Syed
Affiliations
Kollur Shiva Prasad
Department of Sciences, Amrita School of Arts and Sciences, Amrita Vishwa Vidyapeetham, Mysuru 5700 26, Karnataka, India
Renjith Raveendran Pillai
Central Polytechnic College, Vattiyoorkavu, Trivandrum 695013, Kerala, India
Chandan Shivamallu
Division of Biotechnology and Bioinformatics, School of Life Sciences, JSS Academy of Higher Education & Research, Mysuru 570 015, Karnataka, India
Shashanka K. Prasad
Division of Biotechnology and Bioinformatics, School of Life Sciences, JSS Academy of Higher Education & Research, Mysuru 570 015, Karnataka, India
Anisha S. Jain
Department of Physics, T.K.M. College of Arts and Science, Karicode, Kollam 691 005, Kerala, India
Sushma Pradeep
Division of Biotechnology and Bioinformatics, School of Life Sciences, JSS Academy of Higher Education & Research, Mysuru 570 015, Karnataka, India
Stevan Armaković
Department of Physics, Faculty of Sciences, University of Novi Sad, Trg D. Obradovića 4, Novi Sad 21000, Serbia
Sanja J. Armaković
Department of Chemistry, Biochemistry and Environmental Protection, Faculty of Sciences, University of Novi Sad, Trg D. Obradovića 3, Novi Sad 21000, Serbia
Chandrashekar Srinivasa
Department of Biotechnology, Davangere University, Shivagangotri, Davangere 577 007, Karnataka, India
Sharadadevi Kallimani
Department of PG Studies & Research in Food Technology, Davangere University, Shivagangotri, Davangere 577 007, Karnataka, India
Raghavendra G. Amachawadi
Department of Clinical Sciences, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA
Veena Malligere Ankegowda
Department of Chemistry, Bangalore Institute of Technology, K.R. Road, V V Puram, Bangalore 560 004, Karnataka, India
Najat Marraiki
Department of Botany and Microbiology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia
Abdallah M. Elgorban
Department of Botany and Microbiology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia
Asad Syed
Department of Botany and Microbiology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia
Herein we report the synthesis and structural elucidation of two novel imine-based ligands, 2-(1,10-phenanthrolin-5-yl)imino)methyl)-5-bromophenol (PIB) and N-(1,10-phenanthrolin-5-yl)-1-(thiophen-3-yl)methanimine (PTM) ligands. An in vitro cytotoxicity assay of the synthesized molecules was carried out against breast, cervical, colorectal, and prostate cancer cell lines as well as immortalized human keratinocytes. The observations indicated that both the molecules possesses dose-dependent selective cytotoxicity of cancer cells with no detrimental effect on the normal cell lines. Furthermore, the detailed computational analysis of newly synthetized ligands (PIB and PTM) has been conducted in order to identify their most important parts from the perspective of local reactivity. The IC50 values of PIB treatment on MCF-7, HeLa, HCT-116 and PC-3 were 15.10, 16.25, 17.88, 17.55 and 23.86 micromoles, respectively. Meanwhile, the IC50 values of PTM on MCF-7, HeLa, HCT-116, PC-3 and HaCat were observed to be 14.82, 15.03, 17.88, 17.28 and 21.22 micromoles, respectively. For computational analysis, we have employed the combination of Density Functional Theory (DFT) calculations and MD simulations. DFT calculations provided us with information about structure and reactivity descriptors based on the electron distribution. Surfaces of molecular electrostatic potential (MEP) and averaged local ionization energy (ALIE) indicated the sites within studied molecules that are most reactive. These results indicated the importance of nitrogen atoms and OH group. Additionally, the values of bond dissociation for hydrogen abstraction showed that both molecules, especially the PTM, are stable toward the influence of autoxidation mechanism. On the other side, MD simulations gave us an insight how ligands interact with water molecules. Namely, the radial distribution functions (RDF) indicated that the hydrogen atom of the OH group in the case of the PIB has the most pronounced interactions with water.
