Folia Medica 63(2): 213-220, doi: 10.3897/folmed.63.e52891
Regioselective synthesis of triazolo[3,4-e]purine derivatives and their anti-cancer activity against NCI-60 cell-lines
expand article infoKhushal Kapadiya, Kishor Kavadia§, Jyoti Gohel§, Ranjan Khunt§
‡ RK University, Rajkot, India§ Saurashtra University, Rajkot, India
Open Access

Introduction: Due to the vast medicinal importance of purine nucleoside, a hybrid molecule of triazole with purine ring might 
explode a lead molecule in the pharma sector and based on the last decade’s studies suggested that the nitrogen-rich molecules possess a wide range of medicinal importance.

Aim: Due to the vast application of purine nucleoside itself in the field of cancer research, we synthesized triazolo[3,4-e]purines and screened them for their anti-cancer study against NCI-60 cell lines by the protocol used by NIH.

Materials and methods: The targeted molecules, 4-chloro-5a,6-dihydro-8-substitutedphenyl-1H-[1,2,4]triazolo[3,4-e]purine 
derivatives (4a-4h) were synthesized in a two-step procedure by nucleophilic substitution (SN) at C-2 chlorine followed by formation of the triazole ring by acid-catalyzed reaction in the polar protic solvent.

Results: It was observed that the regioselective approach followed in C-2 chlorine replacement instead of C-6 chlorine during SN reaction. One-dose response of selected three molecules (4a, 4b, and 4c) showed that 4b (K-562: 64.47 µM & SR: 63.38 µM; mean GI50: 99.09 µM) was found to be more potent than 4a and 4c.

Conclusions: We have described in this study the general synthetic method for triazolo[3,4-e]purines as an innovative class of potential anticancer agents. The dose-response curve in the sense of mean GI50 for three compounds across all 60 cell lines, 4b can be served as lead after necessary modification.

in vitro anticancer activity, purines, triazolopurines