Design,synthesis and in vitro anticancer evaluation of 4,6-diamino-1,3,5-triazine-2-carbohydrazides and -carboxamides |
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Authors: | Hend Kothayer Abdalla A Elshanawani Mansour E Abu Kull Osama I El-Sabbagh Malathy PV Shekhar Andrea Brancale Arwyn T Jones Andrew D Westwell |
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Institution: | 1. School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Redwood Building, King Edward VII Avenue, Cardiff CF10 3NB, Wales, UK;2. Faculty of Pharmacy, Zagazig University, Egypt;3. Faculty of Pharmacy, Taif University, Taif, Saudi Arabia;4. Karmanos Cancer Institute, 110 E. Warren Avenue, Detroit, MI 48201, USA |
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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. |
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Keywords: | E2 ubiquitin conjugating enzyme Rad6B Triazines Breast cancer MDA-MB-231 MCF-7 |
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