New N-ribosides and N-mannosides of rhodanine derivatives with anticancer activity on leukemia cell line: Design, synthesis, DFT and molecular modelling studies.

Ahmed I Khodair, Mohamed K Awad, Jean-Pierre Gesson, Yaseen A M M Elshaier

Carbohydrate research 2020 Jan

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N-ribosylation and N-mannosylation compounds have a great role in compounds activity as anticancer. The reaction of 2-thioxo-4-thiazolidinone (rhodanine) derivatives, as aglycon part, was done with ribofuranose and mannopyranose sugars (glycone part) followed by deacetylation without cleavage of the rhodanine under acidic medium. Conformational analysis has been studied using NMR methods (2D, DQF-COSY, HMQC and HMBC). All final the new deprotected nucleosides were screened against leukemia 1210, and were found to be considerably less potent (Ic50% 1.4-10.6 μM) than doxorubicin (Ic50% 0.02 μM). Compounds 10d and 10e which contain ribose moiety have better activity than those with mannose sugar. DFT calculations with B3LYP/6-31 + G (d) level were used to analyze the electronic and geometric characteristics deduced from the stable structure of the compounds. The principal quantum chemical descriptors showed a good correlation with the experimental observations. Rapid Overlay Comparison Similarity (ROCS) study was operated to explain the compounds similarity and to figure out the most important pharmacophoric features. Copyright © 2019 Elsevier Ltd. All rights reserved.

Citation

Ahmed I Khodair, Mohamed K Awad, Jean-Pierre Gesson, Yaseen A M M Elshaier. New N-ribosides and N-mannosides of rhodanine derivatives with anticancer activity on leukemia cell line: Design, synthesis, DFT and molecular modelling studies. Carbohydrate research. 2020 Jan;487:107894