Small molecules have potential usage in cancer therapy due to their remarkable potency of disarranging the natural structure of nucleic acids. In this study, two complexes [Pt(NH3)2(IBgly)]NO3(1) and [Pt(bipy)(IBgly)]NO3 (2) based on Pt(II), N-isobutylglycine (IBgly), 2,2′-bipyridine, and ammonia were prepared and characterized by spectroscopic methods. Pharmacokinetic ADME data, absorption, distribution, metabolism, excretion, and bioavailability radar showed two complexes can be introduced for Pt-based anti-cancer drugs. Mechanism of tumor inhibition and DNA interaction of these compounds was studied by UV–Vis, fuorescence, and CD spectroscopies. Also, thermodynamic parameters and the binding constants were calculated through absorption measurements. The fluorescence data showed that a static quenching mechanism occurred for both complexes with a binding constant and binding afnity towards DNA (Kb≈3500  M−1 and kq≈2.1× 1011 M−1 s−1). The thermodynamic parameters indicated electrostatic approaching and groove binding were more feasible than intercalation mode between Pt(II) complexes and DNA. CD spectra indicated the increasing intensity of the positive band and the negative band decreasing. Density functional theory calculations confrmed the experimental data and determined the quantum chemical descriptors including total energy, hardness, chemical potential, electrophilicity, electronegativity, etc. According to this, the binding tendency of these compounds with DNA could be predicted. Further, molecular docking studies were also performed. Docking studies revealed that the desolvation, hydrogen, and elec- trostatic binding were efective for the interaction between complexes and DNA with binding energy (−10.44 and−9.57 kcal/mol) for complexes 1 and 2, respectively, which is mainly of partially electrostatic and groove binding type. The cytotoxic activity of Pt complexes was examined against human colon cancer cell line which indicated good activity with IC50 values of (41.66 and 47.30  μM) for both complexes after 72 h, respectively. Also, they demonstrated more inhibitory efects compared to carboplatin.

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