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Synthesis and Biological Evaluation of New Functionalized Nitroindazolylacetonitrile Derivatives
Author(s) -
Eddahmi Mohammed,
Moura Nuno M. M.,
Bouissane Latifa,
Faustino Maria A. F.,
Cavaleiro José A. S.,
Paz Filipe A. A.,
Mendes Ricardo F.,
Figueiredo Joana,
Carvalho Josué,
Cruz Carla,
Neves Maria G. P. M. S.,
Rakib El Mostapha
Publication year - 2019
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.201904344
Subject(s) - chemistry , hela , knoevenagel condensation , alkylation , salicylaldehyde , combinatorial chemistry , hydrolysis , imine , indazole , piperidine , stereochemistry , organic chemistry , schiff base , catalysis , biochemistry , cell
The versatility of N ‐methyl‐nitroindazolylacetonitriles as templates for further modifications was evidenced by their successfully alkylation with a series of alkyl halides using DBU as base affording the monoalkylated derivatives in high yields. Another synthetic strategy used to modify the nitroindazolylacetonitrile derivatives was the Knoevenagel condensation with a series of aldehydes in the presence of piperidine; such condensation allowed the preparation of the desired products in good to excellent yields. The reaction of a series of nitroindazolylacetonitriles with salicylaldehyde showed to be an efficient and fast methodology to prepare chromenone‐imine‐indazoles (83‐92%), which by acid hydrolysis were converted into the corresponding chromenone‐indazole derivatives (88‐94%). The structures of derivatives 8 h , 8 l and 10 were unequivocally confirmed by single crystal X‐ray diffraction. The drug‐likeness properties of the compounds were evaluated in silico and none of the tested nitroindazolylacetonitriles violated the Lipinski's “rule of five”. The antiproliferative activity against human cervical cancer cells (HeLa) and normal human dermal fibroblasts was evaluated by MTT assay and revealed that compounds 7 b , 8 d and 14 a are those who presented higher antiproliferative effect against HeLa cancer cells.