Design, synthesis and in vitro anticancer evaluation of 4,6-diamino-1,3,5-triazine-2-carbohydrazides and -carboxamides

Triazine as a promising scaffold for its versatile biological behavior

“…13). Westwell and co-workers [58] has been synthesized a series of triazine substituted carbohydrazides and carboxamides as potential anticancer agents targeting Rad6B that led to the discovery of a number of compounds with low micromolar IC 50 …”

A Systematic Review on Antitumor Agents with 1, 3, 5-triazines

“…The triazine carboxamide (Figure 19) was the highest active compound against MCF-7 cell line. From molecular docking studies, TZ8 and compound 61 were incorporated deep inside the Rad6B binding pocket, making key interactions between the hydrazine nitrogen atoms and the Rad6B active site residues Cys88 and Asp90 (Figure 20) [147]. cellular proteins [143].…”

Synthesis and in vitro anticancer evaluation of some 4,6-diamino-1,3,5-triazine-2-carbohydrazides as Rad6 ubiquitin conjugating enzyme inhibitors

“…2) with IC 50 values (2.48–4.79 μM) superior to those of TZ8 and TZ9 when tested on the Rad6B-expressing MDA-MB-231 cell line 24 . In docking studies, such triazinecarbohydrazide derivatives were found to be incorporated deep inside the Rad6B binding pocket, making key interactions between the hydrazine nitrogen atoms and the Rad6B active site residues Cys88 and Asp90.…”

“…Additional interactions between the aniline nitrogens and Asn119/Gln93 and between the phenyl (hydrazide) ring and Leu89 were also apparent from our docking analysis. The importance of these active site residues to the allosteric effect on Rad6B induced by E3 ligases, and the observation that no other E2 family members (with the exception of Rad6A) have residues corresponding to Gln93 or Asn119, suggest that these triazinecarbohydrazides could be selective Rad6B inhibitors 24 .…”