Synthesis, characterization, DNA binding, topoisomerase inhibition, and apoptosis induction studies of a novel cobalt(III) complex with a thiosemicarbazone ligand

Abstract

× 10 5 and 1.6 × 10 4 M −1 , respectively). Topoisomerase inhibition assays and cleavage studies proved that complex 4 was an efficient catalytic inhibitor of human topoisomerases I and IIα. Based upon the results obtained from the 3-(4,5-dimethylthiazol-2-yl)-5-(3carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay on 4T1-luc metastatic mammary breast cancer cells (IC 50 = 34.4 ± 5.2 μM when compared to IC 50 = 13.75 ± 1.08 μM for the control, cisplatin), further investigations into the molecular events initiated by exposure to complex 4 were investigated. Studies have shown that complex 4 activated both the apoptotic and autophagic signaling pathways in addition to causing dissipation of the mitochondrial membrane potential (ΔΨ m). Furthermore, activation of cysteine-aspartic proteases3 (caspase 3) in a time-and concentration-dependent manner coupled with the ΔΨ m , studies implicated the intrinsic apoptotic pathway as the major regulator of cell death mechanism.

Research Progress on the Biological Activities of Metal Complexes Bearing Polycyclic Aromatic Hydrazones

“…The coordination configurations of these Ru(II) complexes are similar to those of the mixed ligand Co(III) complexes of 9-anthrahydrazone and o -phenanthroline/bipyridine, as previously reported by Alvin A. Holder et al [ 119 ]. Competitive fluorescence analysis of DNA and DNA viscosity experiments conducted using ethidium bromide (EB) as a probe showed that the two Ru(II) complexes bind to DNA via intercalation with a strong binding ability.…”

“…Alvin A. Holder’s team [ 118 , 119 ] also attempted to synthesize a novel vanadium(IV) complex and cobalt(III) complex of 9-anthrahydrazone with methyl thiourea as a side chain by introducing different co-ligands ( Figure 39 ). In 2012, they reported the synthesis of a lead complex with tryptophan, salicylic acid, and VOSO 4 and further mix-coordinated with the above 9-anthrahydrazone ligand to synthesize a new V(IV) complex as well as two other V(IV) complexes of non-anthrahydrazone ligands.…”

“…Subsequently, in 2020, they further synthesized a novel Co(III) complex using the same 9-anthrahydrazone ligand by introducing o -phenanthroline as a co-ligand ( Figure 40 ) [ 119 ]. The 9-anthrahydrazone and two o -phenanthrenes both coordinated with Co(III) via N / S - and N / N -bidentate chelation modes, respectively, to form a hexahedral complex.…”

Antibacterial Activity of a Cationic Antimicrobial Peptide against Multidrug-Resistant Gram-Negative Clinical Isolates and Their Potential Molecular Targets

“…where [DNA] refers to DNA concentration and ε a , ε b and ε f represent apparent, fully bonded, and free molar extinction coefficients of the peptide, respectively [64][65][66]. The Wolf-Shimer plots, using absorbance of the peptide at 257 nm vs. CT-DNA and gDNA-1gDNA2 concentration, is shown in Figure 4.…”

UHPLC/GC‐TOF‐MS metabolomics, MTT assay, and molecular docking studies reveal physostigmine as a new anticancer agent from the ethyl acetate and butanol fractions ofKigelia africana(Lam.) Benth. fruit extracts

“…Topoisomerases are enzymes implicated in DNA replication during cell division. They are upregulated in cancer cells and are, therefore, the targets of anticancer drugs (Azarova et al, 2007; Beebe et al, 2019; Pommier, 2013; Wang, 2002). Clinically successful anticancer agents, such as doxorubicin and camptothecin, act through the poisoning of topoisomerases, leading to the formation of double‐strand break and ultimately replication fork arrest (Amin, Gali‐Muhtasib, Ocker, & Schhneider‐stock, 2009; Delgado, Hsieh, Chan, & Hiasa, 2018; Irfan et al, 2020).…”