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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. 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. 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 anti-cancer activity, but exhibits antiviral activity [13]. It can be assumed that the possibility of the
formation of [Pharmacophore-Biomolecule] complex by hydrogen bonding ([H-B]) mechanism with protein molecules increases.
Anti-Cancer Potential of Synthetic Oleanolic Acid Derivatives and Their Conjugates with NSAIDs
