Abstract
The design of drug structures that are non-toxic, easily transported and permeable to cellular barriers is currently one of the most growing research trends. Indeed, the structural similarity of 2-hydrazinopyrazine (2HP) to pyrazinamide, which has been successfully used in anti-tuberculosis therapy, makes 2HP a promising research object. Thus, herein, a complete analysis of the structure of 2HP and its physicochemical and cytotoxic properties was performed. Calf thymus DNA (CT-DNA) and bovine serum albumin (BSA) binding studies were conducted, which demonstrated the higher affinity of 2HP to BSA. Furthermore, cytotoxicity tests were performed, which proved that 2HP was non-toxic to human skin keratinocyte cells. Accordingly, 2HP was initially classified as a compound with potential application. Physicochemical investigations were performed using a wide range of experiments, which were supported by DFT calculations using the B3LYP functional and 6-311+G** basis set. The good correlation, high quality and correctness of the obtained parameters were proven although the data was obtained using independent techniques. Additionally, 42 tautomeric (prototrophic) forms of 2HP were found by searching the conformational hyperspace. The most energy stable 2HP conformer structure and the partial charge distribution were established. The preferred 2HP ionic forms preferred were presented, and models of the equilibrium occurring in aqueous solution were proposed. The hydrophilic character of 2HP was established based on the partition coefficient values determined by both experiment and theory. The PCM and SMD solvent models of water and n-octanol were used.
Highlights
In recent years, compounds with aromatic and nitrogencontaining heterocyclic moieties represent the largest group of used medicines
The concentration of the freshly prepared Calf thymus DNA (CT-DNA) was calculated based on the absorbance value at 260 nm and the calibration curve [3DNA 6600 per M per cm].53 2HP was dissolved in Tris–HCl to give 10 mL of solution at a mass concentration equal to 0.18 mM, which was used as the initial and pure pyrazine derivative sample for both types of titration
The 2HP molecule with the pyrazine ring substituted in the second position with a hydrazine group was characterized in the minimum of the potential energy surface by a planar ring, with the nitrogen framework of the substituent being almost co-planar
Summary
Compounds with aromatic and nitrogencontaining heterocyclic moieties represent the largest group of used medicines. It is well known that proton transfer is one of the most fundamental and crucial reactions in nature, and the comprehension and prediction of its pathway and dissociation constants are signi cant This physicochemical parameter is bene cial to de ne and comprehend the biological activity and behavior of active substances at the molecular level in the cell or biochemical processes (absorption, distribution, metabolism, and excretion), and their permeability, bioavailability and formulation.. The interactions of small molecules known as drugs or ligands with DNA have been the subject of recent research in the eld of life sciences, medical chemistry, biochemistry, and bioinorganic or coordination chemistry These are important studies in the context of the impact of a compound with possible biological use. All solutions were prepared directly before the experiments using Hydrolab-Reference puri ed water with conductivity not exceeding 3.0 mS cmÀ1
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