Background: 2-amino-3-cyanopyridines are good starting reagents that have been used in synthesis
of many heterocyclic compounds such as pyridopyrimidines, [1,2,4]triazolo and [1,2,3,4] tetrazolo derivatives
which have biological activities as anti-microbial and cytotoxic activities. Meanwhile [1,2,4]triazolo and
[1,2,3,4]tetrazolo derivatives are well known to possess many physiological activities, such as anticancer ,
antifungal, muscle relaxant, hypnotic, anti-inflammatory, diuretic and antihypertensive activities. A broad class
of heterocyclic compounds has been studied to demonstrate their biological activity on the structures of DNA
and RNA. Several of important functions make Tankyrases acts as targets in potential drug.
Objective: The article focuses on synthesis of [1,2,4]triazolo and [1,2,3,4]tetrazolo derivatives and their
theoretical calculations that suggest they are anti-cancer substances.
Materials and Methods: DFT and computational studies were performed on the structural properties of
experimental molecules experimentally, and significant theoretical calculations were performed based on
density functional theory (DFT) with Becke’s three-parameter exchange function21-22 of correlation
functional Lee Yang Parr (B3LYP) with the basis set 6-31G (d,p) using Gaussian 03 software23. Geometrical
parameters of the optimized structures were calculated and also the charge on each atom (Mulliken charge).
Chemcraft program24 was used to visualize the optimized structure and ChemBio3D ultra 12.0 was used to
visualize the highest occupied and lowest unoccupied molecular orbitals.
Results: Preliminary screening in five studied ligands acts as inhibitors for different active sites along the
target. The molecular docking study also revealed that the compound 6c was the most effective compounds in
inhibiting Tankyrase I enzyme (2rf5), this result can help strongly in inhibition of carcinogenic cells and cancer
Conclusion: We have described a new practical cyclocondensation synthesis for a series of [1,2,4]triazolo[4,3-
c]pyrido[3,2-e] pyrimidine and pyrido[2',3':4,5] pyrimido[6,1-c][1,2,4] triazine from 2-amino-3-cyano-4.6-
diarylpyridines. Also polyheterocyclic compounds containing [1,2,4]triazolo and [1,2,3,4]tetrazolo moieties
were also synthesized through the reactions of 3-hydrazino-8,10-diaryl [1,2,4]triazolo[4,3-c]pyrido[3,2-
e]pyrimidine with both formic acid and the formation of diazonuim salt respectively. Newly synthesized
heterocycles structures were confirmed using elemental analysis, IR, 1H-NMR, 13C-NMR and mass spectral
data. DFT and computational studies were carried out on five of the synthesized poly heterocyclic compounds
to show their structural and geometrical parameters involved in the study. Molecular docking using Tankyrase
I enzyme as a target showed how the studied heterocyclic compounds act as a ligand interacting most of active
sites on Tankyrase I with a type of interactions specified for H-bonding and VDW. We investigated that the
five studied ligands act as inhibitors for different active sites along the target. The molecular docking study
also revealed that the compound 6c was the most effective compounds in inhibiting Tankyrase I enzyme (2rf5),
this result can help strongly in inhibition of carcinogenic cells and cancer treatment.