Synthesis, Electronic Structure And Anti-Cancer Activity Of The Phenyl Substituted Pyrazolo[1,5-A][1,3,5]Triazines

Background: Synthesis of a series of 2-(dichloromethyl)pyrazolo[1,5-a][1,3,5]triazines was carried out and evaluated in vitro for their anticancer activity against a panel of 60 cell lines derived from nine cancer types.Methods: The joint quantum-chemical and experimental study of the influence of the ex-tended (pi) over tilde conjugated phenyl substituents on the electron structure of the pyrazolo[1,5-a][1,3,5]triazines as Pharmacophores were performed. It is shown that the decrease in the barriers to the rotation of phenyl substituents in compounds 1-7 possibly leads to an increase in the anti-cancer activity, which is in agreement with the change in the parameter biological affinity phi(0). Analysis of the S-0 -> S-1 electronic transitions (pi ->pi*) of the pyrazolo[1,5-a][1,3,5]triazines shows that an increase in their intensity correlates with anti-cancer activity.Results: Thus, the introduction of phenyl substituents increases the likelihood of investigated pyrazolo[1,5-a][1,3,5]triazines interacting with protein molecules (Biomolecule) by the (pi) over tilde -stacking mechanism. In both methyl and phenyl derivatives of pyrazolo[1,5-a][1,3,5]triazines, the second electronic transition includes the n -MO (the level of the lone electron pair in two-coordinated nitrogen atoms). The highest intensity of the eta ->pi* elec-tronic transition is observed in pyrazolo[1,5-a][1,3,5]triazine with pyridine residue, which does not exhibit anti-cancer activity, but exhibits antiviral activity [13].Conclusion: It can be assumed that the possibility of the formation of [Pharmacophore-Biomolecule] complex by hydrogen bonding ([H-B]) mechanism with protein molecules increases.