TY - JOUR
T1 - Water-Soluble mono- and binuclear Ru(η6- p -cymene) complexes containing indole thiosemicarbazones
T2 - Synthesis, DFT modeling, biomolecular interactions, and in vitro anticancer activity through apoptosis
AU - Haribabu, Jebiti
AU - Sabapathi, Gopal
AU - Tamizh, Manoharan Muthu
AU - Balachandran, Chandrasekar
AU - Bhuvanesh, Nattamai S.P.
AU - Venuvanalingam, Ponnambalam
AU - Karvembu, Ramasamy
N1 - Funding Information:
J.H. thanks the University Grants Commission for a fellowship (F1-17.1/2012-13/RGNF-2012-13-ST-AND-18716). P.V. thanks the Council of Scientific and Industrial Research for the award of an Emeritus Scientistship (No. 21(0936)/12/ EMR-II), Department of Science and Technology (DST) of India, for a Major Research Project (SB/S1/PC-52/2012) and the DST-PURSE HPC facility (SR/FT/LS-113/2009) of Bharathidasan University.
Publisher Copyright:
© 2018 American Chemical Society.
PY - 2018/4/23
Y1 - 2018/4/23
N2 - Indole thiosemicarbazone ligands were prepared from indole-3-carboxaldehyde and N-(un)substituted thiosemicarbazide. The Ru(η6-p-cymene) complexes [Ru(η6-p-cymene)(HL1)Cl]Cl (1) and [Ru(η6-p-cymene)(L2)]2Cl2 (2) were exclusively synthesized from thiosemicarbazone (TSC) ligands HL1 and HL2, and [RuCl2(p-cymene)]2. The compounds were characterized by analytical and various spectroscopic (electronic, FT-IR, 1D/2D NMR, and mass) tools. The exact structures of the compounds (HL1, HL2, 1, and 2) were confirmed by single-crystal X-ray diffraction technique. In complexes 1 and 2, the ligand coordinated in a bidentate neutral (1)/monobasic (2) fashion to form a five-membered ring. The complexes showed a piano-stool geometry around the Ru ion. While 2∗ existed as a dimer, 1 existed as a monomer, and this was well explained through free energy, bond parameter, and charge values computed at the B3LYP/SDD level. The intercalative binding mode of the complexes with calf thymus DNA (CT DNA) was revealed by spectroscopic and viscometric studies. The DNA (pUC19 and pBR322 DNA) cleavage ability of these complexes evaluated by an agarose gel electrophoresis method confirmed significant DNA cleavage activity. Further, the interaction of the complexes with bovine serum albumin (BSA) was investigated using spectroscopic methods, which disclosed that the complexes could bind strongly with BSA. A hemolysis study with human erythrocytes revealed blood biocompatibility of the complexes. The in vitro anticancer activity of the compounds (HL1, HL2, 1, and 2) was screened against two cancer cell lines (A549 and HepG-2) and one normal cell line (L929). Interestingly, the binuclear complex 2∗ showed superior activity with IC50 = 11.5 μM, which was lower than that of cisplatin against the A549 cancer cell line. The activity of the same complex (IC50 = 35.3 μM) was inferior to that of cisplatin in the HepG-2 cancer cell line. Further, the apoptosis mode of cell death in the cancer cell line was confirmed by using confocal microscopy and DNA fragmentation analysis.
AB - Indole thiosemicarbazone ligands were prepared from indole-3-carboxaldehyde and N-(un)substituted thiosemicarbazide. The Ru(η6-p-cymene) complexes [Ru(η6-p-cymene)(HL1)Cl]Cl (1) and [Ru(η6-p-cymene)(L2)]2Cl2 (2) were exclusively synthesized from thiosemicarbazone (TSC) ligands HL1 and HL2, and [RuCl2(p-cymene)]2. The compounds were characterized by analytical and various spectroscopic (electronic, FT-IR, 1D/2D NMR, and mass) tools. The exact structures of the compounds (HL1, HL2, 1, and 2) were confirmed by single-crystal X-ray diffraction technique. In complexes 1 and 2, the ligand coordinated in a bidentate neutral (1)/monobasic (2) fashion to form a five-membered ring. The complexes showed a piano-stool geometry around the Ru ion. While 2∗ existed as a dimer, 1 existed as a monomer, and this was well explained through free energy, bond parameter, and charge values computed at the B3LYP/SDD level. The intercalative binding mode of the complexes with calf thymus DNA (CT DNA) was revealed by spectroscopic and viscometric studies. The DNA (pUC19 and pBR322 DNA) cleavage ability of these complexes evaluated by an agarose gel electrophoresis method confirmed significant DNA cleavage activity. Further, the interaction of the complexes with bovine serum albumin (BSA) was investigated using spectroscopic methods, which disclosed that the complexes could bind strongly with BSA. A hemolysis study with human erythrocytes revealed blood biocompatibility of the complexes. The in vitro anticancer activity of the compounds (HL1, HL2, 1, and 2) was screened against two cancer cell lines (A549 and HepG-2) and one normal cell line (L929). Interestingly, the binuclear complex 2∗ showed superior activity with IC50 = 11.5 μM, which was lower than that of cisplatin against the A549 cancer cell line. The activity of the same complex (IC50 = 35.3 μM) was inferior to that of cisplatin in the HepG-2 cancer cell line. Further, the apoptosis mode of cell death in the cancer cell line was confirmed by using confocal microscopy and DNA fragmentation analysis.
UR - http://www.scopus.com/inward/record.url?scp=85045926452&partnerID=8YFLogxK
U2 - 10.1021/acs.organomet.8b00004
DO - 10.1021/acs.organomet.8b00004
M3 - Article
AN - SCOPUS:85045926452
SN - 0276-7333
VL - 37
SP - 1242
EP - 1257
JO - Organometallics
JF - Organometallics
IS - 8
ER -