Design of DNA-intercalators based copper(II) complexes, investigation of their potential anti-cancer activity and sub-chronic toxicity

Publication date: December 2019Source: Materials Science and Engineering: C, Volume 105Author(s): Vishnu Sravan Bollu, Thulasiram Bathini, Ayan Kumar Barui, Arpita Roy, Nagarjuna Chary Ragi, Swamy Maloth, Prabhakar Sripadi, Bojja Sreedhar, Penumaka Nagababu, Chitta Ranjan PatraAbstractIn the present paper, we synthesized and characterized four N-donor polypyridyl copper(II) complexes (C1-C4); [Cu(mono-CN-PIP)2]2+ (C1), [Cu(tri-OMe-PIP)2]2+ (C2), [Cu(di-CF3-PIP)2]2+ (C3) and [Cu(DPPZ)2]2+ (C4). The (Calf-Thymus) CT-DNA binding studies depicted that the complexes could interact with DNA via intercalative mode. All the complexes, particularly C3 and C4 attenuated the proliferation as well as migration of various cancer cells, indicating their anti-cancer and anti-metastatic activity. Additionally, chick embryo angiogenesis (CEA) assay exhibited the inhibition of vascular sprouting in presence of C3 and C4, suggesting their potential in inhibiting the blood vessel growth. Mechanistic studies revealed that the complexes induced the excessive production of cellular reactive oxygen species (ROS) leading to apoptosis through up regulation of p53 and downregulation of Bcl-xL, which might be the plausible mechanisms underlying their anti-cancer properties. To understand the feasibility of practical application of anti-cancer copper complexes C3 and C4, in vivo sub-chronic toxicity study (4 weeks) was performed in C57BL6 mice and the results exhibited almost non-toxic effects induced ...
Source: Materials Science and Engineering: C - Category: Materials Science Source Type: research