The interaction of new dinuclear copper(II) complex 1; [Cu₂(glygly)₂(ppz)(H₂O)₄]·2H₂O, derived from dipeptide (glycyl glycine) and piperazine as a metallopeptide drug with human serum albumin (HSA) was examined by means of fluorescence spectroscopy which revealed that complex 1 has a strong ability to quench the intrinsic fluorescence of HSA through a static quenching procedure. The alterations of HSA secondary structure in the presence of complex 1 were confirmed by UV-visible, FT-IR, CD and 3D fluorescence spectroscopy. The binding constants (K), and binding site number (n), corresponding thermodynamic parameters ΔG, ΔH and ΔS at different temperatures were calculated. The molecular docking technique was utilized to ascertain the mechanism and mode of action towards the molecular target HSA indicating that complex 1 was located at the entrance of site I by electrostatic and hydrophobic forces, consistent with the corresponding experimental results. Complex 1 shows efficient photo-induced HSA cleavage activity, indicating the involvement of hydroxyl radicals as the reactive species. Furthermore, the cytotoxicity of 1 was examined on a panel of human tumor cell lines of different histological origins showing significant GI₅₀ values specifically towards MIAPACA2, A498 and A549 tumor cell lines. These results complement previous biological studies of new specific target metallopeptides, providing additional information about possibilities of their transport and disposition in blood plasma.

New molecular topologies quercetin–Cu^II–Sn₂ ^IV and Zn^II–Sn₂ ^IV1 and 2 were designed and synthesized to act as potential cancer chemotherapeutic agents. Their interaction with CT DNA by UV-vis and fluorescence spectroscopy was evaluated revealing an electrostatic mode of binding. Quercetin complexes are capable of promoting DNA cleavage involving both single and double strand breaks. Complex 1 cleaved pBR322 DNA via an oxidative mechanism while 2 followed a hydrolytic pathway, accessible to the minor groove of the DNA double helix in accordance with molecular docking studies with the DNA duplex of sequence d(CGCGAATTCGCG)₂ dodecamer demonstrating that the complex was stabilized by additional electrostatic and hydrogen bonding interactions with the DNA. ROS such as OH˙, H₂O₂ and O₂˙⁻ are the major metabolites responsible for chronic diseases such as cancer, respiratory disorders, HIV, and diabetes etc., therefore eliminating ROS by molecular scaffolds involving SOD enzymatic activity has emerged as a potential way to develop a novel class of drugs. Therefore, in vitro superoxide dismutase activity of redox active complex 1 was evaluated by using a xanthine/xanthine oxidase-NBT assay which showed an IC₅₀ value of 2.26 μM. Moreover, the cytotoxicity of both the complexes were screened on a panel of human carcinoma cell lines (GI₅₀ values <8.7 μM) which revealed that 1 has a better prospect of acting as a cancer chemotherapeutic agent, and to elucidate the mechanism of tumor inhibition, Topo-I enzymatic activity was carried out. Furthermore, molecular modeling studies were carried out to understand molecular features important for drug–enzyme interactions which offer new insights into the experimental model observations.

Diorganotin(IV) complexes 1–3 (R = Me, 1; Bu, 2; Ph, 3) derived from the ligand N′-(4-hydroxypent-3-en-2-ylidene)isonicotinohydrazide were synthesized and thoroughly characterized by elemental analysis and spectroscopic techniques (UV-vis, IR, ¹H, ¹³C and ¹¹⁹Sn NMR and ESI-MS). The molecular structure of diphenyltin(IV) complex 3 was further established by single crystal X-ray crystallography which showed that the complex crystallized in the monoclinic space group C21/c. To ascertain the pharmacokinetic and chemotherapeutic aspects of the synthesized diorganotin(IV) complexes 1–3, in vitro interaction studies were carried out with CT DNA/HSA by employing various biophysical methods viz., UV-vis, fluorescence, FT IR (in case of HSA only) and circular dichroism. Notably, all of the complexes exhibited a high propensity for DNA binding via electrostatic modes; the binding affinity was found to be in the order 2 > 3 > 1 and also revealed static quenching of the HSA fluorophore. The experimental findings were validated by density functional theory (DFT) calculations which determined the quantum mechanical (QM) reactivity descriptors viz., single point energy (H), hardness (η), electronic chemical potential (μ), electrophilicity (ω); on that basis the binding trend of the complexes with CT DNA and HSA could be predicted. Further, molecular docking studies were performed to visualize the preferential binding sites of diorganotin(IV) complexes with DNA and HSA. In vitro cytotoxicity of di-n-butyltin(IV) complex 2 was carried out in a panel of human cancer cell lines viz., U373MG (CNS), PC3 (prostrate), Hop62 (lung), HL60 (leukemia), HCT15 (colon), SK-OV-3 (ovarian), HeLa (cervix) and MCF7 (breast) which revealed significantly good activity with GI₅₀ values of <10 μg mL⁻¹ for most of the cell lines tested.

To evaluate the biological preference of metallopeptide drugs in cancer cells, a new dinuclear copper(II) complex [Cu₂(glygly)₂(ppz)(H₂O)₄]·2H₂O (1) (glygly = glycyl glycine anion and ppz = piperazine), was designed and synthesized as topoisomerase I inhibitor. The structural elucidation of the complex was done by elemental analysis, spectroscopic methods and single crystal X-ray diffraction. The in vitro DNA binding studies of complex 1 with CT DNA were carried out by employing different optical methods viz. UV-vis, fluorescence and circular dichroism. The molecular docking technique was also utilized to ascertain the mechanism and mode of action towards the molecular target DNA and enzymes. Complex 1 cleaves pBR322 DNA via an oxidative mechanism and strongly binds to the DNA minor groove. Furthermore, complex 1 exhibits significant inhibitory effects on the catalytic activity of topoisomerase I at a very low concentration, ∼12.5 μM, in addition to its excellent SOD mimics (IC₅₀ ∼ 0.086 μM).