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

Abstract

Series of substituted 4,6-diamino-1,3,5-triazine-2-carbohydrazides and -carboxamides have been synthesised, based on molecular modelling of candidate structures related to the previously reported Rad6B-inhibitory diamino-triazinylmethyl benzoate anticancer agents TZ8 and TZ9. Synthesis of the target compounds was readily accomplished in two steps from aryl biguanides via reaction of phenylhydrazine or benzylamines with key 4-amino-6-(arylamino)-1,3,5-triazine-2-carboxylate intermediates. These new triazine derivatives were tested for in vitro anticancer activity against the Rad6B expressing human breast cancer cell lines MDA-MB-231 and MCF-7. Active compounds, such as the triazinyl-carbohydrazides 3a-e, were found to exhibit low micromolar IC50 values particularly in the Rad6B-overexpressing MDA-MB-231 cell line.

• Authors: Hend Kothayer, Abdalla A Elshanawani, Mansour E Abu Kull, Osama I El-Sabbagh, Malathy P V Shekhar, Andrea Brancale, Arwyn T Jones, Andrew D Westwell
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 23 Issue 24 Pg. 6886-9 (Dec 15 2013) ISSN: 1464-3405 [Electronic] England
• PMID: 24153206 (Publication Type: Journal Article)
• Copyright: Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical References

• Amides
• Antineoplastic Agents
• Hydrazines
• Triazines
• UBE2B protein, human
• Ubiquitin-Conjugating Enzymes
• carbohydrazide

Topics

• Amides (chemical synthesis, chemistry, pharmacology)
• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Binding Sites
• Catalytic Domain
• Cell Line, Tumor
• Cell Survival (drug effects)
• Drug Design
• Humans
• Hydrazines (chemical synthesis, chemistry, pharmacology)
• MCF-7 Cells
• Molecular Docking Simulation
• Structure-Activity Relationship
• Triazines (chemistry)
• Ubiquitin-Conjugating Enzymes (antagonists & inhibitors, metabolism)