A novel Schiff base ligand (L), bearing N₂O₂ donor sites, was derived from the condensation of 5-chloromethylisophthaldehyde and phenylpropanolamine (PPA). Mononuclear Co(II), Cu(II), and Zn(II) complexes were synthesized and were characterized by FTIR, UV–Vis, ¹H NMR, ESI-mass spectroscopy, molar conductance, and thermal and electrochemical studies. The thermal investigation revealed that the complexes were stable up to 150–250 °C and began to degrade in stages, resulting in the development of respective metal oxides. The Coats–Redfern integration method was used to calculate the kinetic and thermodynamic parameters, the energy of activation (Ea), and changes in enthalpy (∆H), entropy (∆S), and free energy (∆G) for each step of the degradation processes. For stage I decomposition, the calculated activation energy values of the complexes follow the order of Ea [Cu(L)] > Ea [Co(L)(H₂O)₂] > Ea [Zn(L)]. The influence of the temperature on the efficacy of antioxidant activities of the complexes with DPPH assay, ABTS assay, and hydroxy radical assay was investigated at various concentrations using ascorbic acid (AA) as the reference. Antioxidant activity was assessed at multiple temperatures to ascertain whether these complexes may be applied in radiation therapy enhanced with hyperthermia and found to be stable. Subsequently, the Cu(II) complex (C2) demonstrated a greater cytotoxicity (IC₅₀ = 5.16 µM) than Co(II), Zn(II), and conventional cisplatin when in vitro cytotoxicity was evaluated against the MCF-7 cell line using the MTT method. Analyses of the thermal stability and ROS scavenging ability of complexes have demonstrated that these complexes have potential in hyperthermic radiation therapy.

A series of 11 compounds of phenyl–imidazole–pyrrole and 9 compounds of phenanthryl–imidazole–pyrrole were synthesized and evaluated against breast cancer cell lines differing in the expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor (HER)-2, viz., BT-474 (ER+, PR+, and HER2+), T-47D and MCF-7 (ER+, PR+, and HER2−), and MDA-MB-468 and MDA-MB-231 (ER−, PR−, and HER2−). The analysis of the results indicated that the most active compounds were 5d and 5k from the phenyl–imidazole–pyrrole series and 6b and 6i from the phenanthryl–imidazole–pyrrole series (IC₅₀ < 50 µM). Molecular docking (MD) and molecular dynamics simulation (MDS) studies demonstrated that the active compounds exhibited high binding affinity to the 7NH5 (a co-crystal structure of Akt1 and its specific inhibitor) protein, which is overexpressed in many breast cancer types. The active compounds 6b and 6i reduced the viability of MDA-MB-231 and MCF-7 cells by inducing cell death mechanisms. Both compounds halted the proliferation by arresting cells in the G0/G1 phase of the cell cycle. The results are similar to those of traditional Cisplatin. Intraperitoneal administration of 6i retarded the development of EAC tumors and increased the survival of mice compared with tumor-bearing control and 5-fluorouracil (5FU)-treated positive control mice.