Heteroleptic Copper(I) Complexes of "Scorpionate" Bis-pyrazolyl Carboxylate Ligand with Auxiliary Phosphine as Potential Anticancer Agents: An Insight into Cytotoxic Mode.
New copper(I) complexes [CuCl(PPh3)(L)] (1: L = LA= 4-carboxyphenyl)bis(3,5-dimethylpyrazolyl)methane; (2: L = LB= 3-carboxyphenyl)bis(3,5-dimethylpyrazolyl)methane) were prepared and characterised by elemental analysis and various spectroscopic techniques such as FT-IR, NMR, UV-Vis, and ESI-MS. The molecular structures of complexes 1 and 2 were analyzed by theoretical B3LYP/DFT method. Furthermore, in vitro DNA binding studies were carried out to check the ability of complexes 1 and 2 to interact with native calf thymus DNA (CT-DNA) using absorption titration, fluorescence quenching and circular dichroism, which is indicative of more avid binding of the complex 1. Moreover, DNA mobility assay was also conducted to study the concentration-dependent cleavage pattern of pBR322 DNA by complex 1, and the role of ROS species to have a mechanistic insight on the cleavage pattern, which ascertained substantial roles by both hydrolytic and oxidative pathways. Additionally, we analyzed the potential of the interaction of complex 1 with DNA and enzyme (Topo I and II) with the aid of molecular modeling. Furthermore, cytotoxic activity of complex 1 was tested against HepG2 cancer cell lines. Thus, the potential of the complex 1 is promising though further in vivo investigations may be required before subjecting it to clinical trials.
Department of Chemistry, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.
Rais Ahmad
RA
Khan
Department of Chemistry, Aligarh Muslim University, Aligarh-202002, India.
Mohammad
M
Usman
National Center for Alternatives for Animal Experiments, Bharathidasan University, Tiruchirappalli, 620024, India.
Rajakumar
R
Dhivya
National Center for Alternatives for Animal Experiments, Bharathidasan University, Tiruchirappalli, 620024, India.
Perumalsamy
P
Balaji
Department of Chemistry, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.
Ali
A
Alsalme
Department of Chemistry, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.|Surfactant Research Chair, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.
Hamad
H
AlLohedan
Department of Chemistry, Aligarh Muslim University, Aligarh-202002, India.
Farukh
F
Arjmand
Department of Chemistry, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.
Khalid
K
AlFarhan
National Center for Alternatives for Animal Experiments, Bharathidasan University, Tiruchirappalli, 620024, India.
Mohammad Abdulkader
MA
Akbarsha
Dipartimento di Scienze Chimiche, Universita´ degli Studi di Camerino, via S. Agostino 1,62032 Camerino, Macerata, Italy.
Fabio
F
Marchetti
Dipartimento di Scienze Chimiche, Universita´ degli Studi di Camerino, via S. Agostino 1,62032 Camerino, Macerata, Italy.
Claudio
C
Pettinari
Department of Chemistry, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.|Department of Chemistry, Aligarh Muslim University, Aligarh-202002, India.|Surfactant Research Chair, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.
Sartaj
S
Tabassum
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D003300:Copper / Q000737:chemistry*; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D004264:DNA Topoisomerases, Type I / Q000737:chemistry / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D062105:Molecular Docking Simulation; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D010720:Phosphines / Q000737:chemistry; D011720:Pyrazoles / Q000737:chemistry
D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D010720:Phosphines; D011720:Pyrazoles; D003300:Copper; D004247:DNA; D004264:DNA Topoisomerases, Type I