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 extended
πconjugated 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 Φ0. Analysis of the S0 → S1 electronic transitions (π→π*) 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 π-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 η→π* electronic
transition is observed in pyrazolo[1,5-a][1,3,5]triazine with pyridine residue, which does not exhibit anticancer
activity, but exhibits antiviral activity .
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.