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

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

  • Bioorg Med Chem Lett. 2013 Dec 15;23(24):6886-9. doi: 10.1016/j.bmcl.2013.09.087.
Hend Kothayer 1,  Abdalla A Elshanawani,  Mansour E Abu Kull,  Osama I El-Sabbagh,  Malathy P V Shekhar,  Andrea Brancale,  Arwyn T Jones,  Andrew D Westwell
Affiliations

Affiliation

  • 1 School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Redwood Building, King Edward VII Avenue, Cardiff CF10 3NB, Wales, UK; Faculty of Pharmacy, Zagazig University, Egypt.
PMID: 24153206 DOI: 10.1016/j.bmcl.2013.09.087
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.

Keywords

Breast cancer; E2 ubiquitin conjugating enzyme; MCF-7; MDA-MB-231; Rad6B; Triazines.

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