Synthesis, crystal structure, molecular docking and cytotoxicity of Zwitterionic 3-(4-amino-3- imino-5-oxo-2,3,4,5-tetrahydro-[1,2,4]triazin-6-yl)-propionic acid

Department of Chemistry, Bharathiar University, Coimbatore-641 046, Tamilnadu, India
Department of Chemistry, VNU University of Science, 19 Le Thanh Tong, Hanoi, Vietnam
E-mail: drsgovind@yahoo.co.in
Manuscript received 13 February 2018, revised 29 March 2018, accepted 31 May 2018

A new 3-(4-amino-3-imino-5-oxo-2,3,4,5-tetrahydro-[1,2,4]triazin-6-yl)-propionic acid monohydrate has been synthesised by the
condensation reaction of α-ketoglutaric acid with diaminoguanidine. The compound exists as zwitter ion, with the hydrogen
atom of carboxylic group being transferred to the exocyclic imine nitrogen atom of triazine moiety. The zwitterionic condensed
product was characterised by single crystal X-ray diffraction, elemental analysis, FT-IR, UV-Vis NMR and Mass spectroscopies,
and TG-DTA methods. This salt crystallises in monoclinic system of space group P2_1/c with a = 6.4871(3) Å, b = 9.1562(5)
Å, c = 14.9555(8) Å, β = 97.519(2)º, Z = 4 and R1/wR2 [/ ≥ 2σ(I)] = 0.0512/0.1092. The structural units are held together by
extensive array of N-H...O, O-H...O and C-H...O interactions and lattice water acts as a linker. The epidermal growth factor
receptor (EGFR) is a tyrosine kinase receptor that is frequently expressed in epithelial tumours. The EGFR was the first receptor
to be proposed as a target for cancer therapy, and the compound was subjected into the target protein in molecular
docking approach. It was observed that the compound decreased the viability of MCF-7 cells in dose dependent level with
the IC₅₀ value of 15.2 µg/mL and the morphology studies indicate that the compound induces apoptosis.