Synthesis, Electronic Structure and Anti-Cancer Activity of the Phenyl Substituted Pyrazolo[1,5-a][1,3,5]triazines

Abstract

: 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 π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 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.

Design, Synthesis, Docking, 2D‐QSAR Modelling, Anticancer and Antioxidant Evaluation of Some New Azo‐Compounds Derivatives and Investigation of Their Fluorescence Properties

“…[2] Hetero cyclization of azo compound is considered as a starting step for the generation of new families of compounds texhibitting various pharmaceutical activities, especially, the cyclization to produce triazine and diazine derivatives where their structures are desirable in a number of bioactive heterocyclic scaffolds with promising biological action. Triazine derivatives showed biological activities including antimicrobial, [3] anti-inflammatory, [4] anti-cancer, [5] antidepressant, [6] anti-bacterial, [7] antifungal, [8] antioxidant, [9] antimalarial, [10] antiproliferative, [11] analgesic activities. [12] In addition, the biological activities of diazine derivatives.…”