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Synthesis and in vitro anticancer activities of substituted N-(4′-nitrophenyl)-l-prolinamides

Prolinamides are present in secondary metabolites and have wide-ranging biological properties as well as antimicrobial and cytotoxic activities. N-(4′-substituted phenyl)-l-prolinamides 4a–4w were synthesized in two steps, starting from the condensation of p-fluoronitrobenzene 1a–1b with l-proline 2...

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Autores principales: Osinubi, Adejoke, Izunobi, Josephat, Bao, Xiaoguang, Asekun, Olayinka, Kong, Jiehong, Gui, Chunshan, Familoni, Oluwole
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7540745/
https://www.ncbi.nlm.nih.gov/pubmed/33047051
http://dx.doi.org/10.1098/rsos.200906
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author Osinubi, Adejoke
Izunobi, Josephat
Bao, Xiaoguang
Asekun, Olayinka
Kong, Jiehong
Gui, Chunshan
Familoni, Oluwole
author_facet Osinubi, Adejoke
Izunobi, Josephat
Bao, Xiaoguang
Asekun, Olayinka
Kong, Jiehong
Gui, Chunshan
Familoni, Oluwole
author_sort Osinubi, Adejoke
collection PubMed
description Prolinamides are present in secondary metabolites and have wide-ranging biological properties as well as antimicrobial and cytotoxic activities. N-(4′-substituted phenyl)-l-prolinamides 4a–4w were synthesized in two steps, starting from the condensation of p-fluoronitrobenzene 1a–1b with l-proline 2a–2b, under aqueous–alcoholic basic conditions to afford N-aryl-l-prolines 3a–3c, which underwent amidation via a two-stage, one-pot reaction involving SOCl(2) and amines, to furnish l-prolinamides in 20–80% yield. The cytotoxicities of 4a–4w against four human carcinoma cell lines (SGC7901, HCT-116, HepG2 and A549) were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay; with good tumour inhibitory activities (79.50 ± 1.24%–50.04 ± 1.45%) against HepG2. 4a exhibited the best anti-tumour activity against A549 with percentage cell inhibition of 95.41 ± 0.67% at 100 µM. Likewise, 4s (70.13 ± 3.41%) and 4u (83.36 ± 1.70%) displayed stronger antineoplastic potencies against A549 than the standard, 5-fluorouracil (64.29 ± 2.09%), whereas 4a (93.33 ± 1.36%) and 4u (81.29 ± 2.32%) outperformed the reference (81.20 ± 0.08%) against HCT-116. SGC7901 showed lower percentage cell viabilities with 4u (8.02 ± 1.54%) and 4w (27.27 ± 2.38%). These results underscore the antiproliferative efficacies of l-prolinamides while exposing 4a and 4u as promising broad-spectrum anti-cancer agents. Structure-activity relationship studies are discussed.
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spelling pubmed-75407452020-10-11 Synthesis and in vitro anticancer activities of substituted N-(4′-nitrophenyl)-l-prolinamides Osinubi, Adejoke Izunobi, Josephat Bao, Xiaoguang Asekun, Olayinka Kong, Jiehong Gui, Chunshan Familoni, Oluwole R Soc Open Sci Chemistry Prolinamides are present in secondary metabolites and have wide-ranging biological properties as well as antimicrobial and cytotoxic activities. N-(4′-substituted phenyl)-l-prolinamides 4a–4w were synthesized in two steps, starting from the condensation of p-fluoronitrobenzene 1a–1b with l-proline 2a–2b, under aqueous–alcoholic basic conditions to afford N-aryl-l-prolines 3a–3c, which underwent amidation via a two-stage, one-pot reaction involving SOCl(2) and amines, to furnish l-prolinamides in 20–80% yield. The cytotoxicities of 4a–4w against four human carcinoma cell lines (SGC7901, HCT-116, HepG2 and A549) were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay; with good tumour inhibitory activities (79.50 ± 1.24%–50.04 ± 1.45%) against HepG2. 4a exhibited the best anti-tumour activity against A549 with percentage cell inhibition of 95.41 ± 0.67% at 100 µM. Likewise, 4s (70.13 ± 3.41%) and 4u (83.36 ± 1.70%) displayed stronger antineoplastic potencies against A549 than the standard, 5-fluorouracil (64.29 ± 2.09%), whereas 4a (93.33 ± 1.36%) and 4u (81.29 ± 2.32%) outperformed the reference (81.20 ± 0.08%) against HCT-116. SGC7901 showed lower percentage cell viabilities with 4u (8.02 ± 1.54%) and 4w (27.27 ± 2.38%). These results underscore the antiproliferative efficacies of l-prolinamides while exposing 4a and 4u as promising broad-spectrum anti-cancer agents. Structure-activity relationship studies are discussed. The Royal Society 2020-09-09 /pmc/articles/PMC7540745/ /pubmed/33047051 http://dx.doi.org/10.1098/rsos.200906 Text en © 2020 The Authors. http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/http://creativecommons.org/licenses/by/4.0/Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.
spellingShingle Chemistry
Osinubi, Adejoke
Izunobi, Josephat
Bao, Xiaoguang
Asekun, Olayinka
Kong, Jiehong
Gui, Chunshan
Familoni, Oluwole
Synthesis and in vitro anticancer activities of substituted N-(4′-nitrophenyl)-l-prolinamides
title Synthesis and in vitro anticancer activities of substituted N-(4′-nitrophenyl)-l-prolinamides
title_full Synthesis and in vitro anticancer activities of substituted N-(4′-nitrophenyl)-l-prolinamides
title_fullStr Synthesis and in vitro anticancer activities of substituted N-(4′-nitrophenyl)-l-prolinamides
title_full_unstemmed Synthesis and in vitro anticancer activities of substituted N-(4′-nitrophenyl)-l-prolinamides
title_short Synthesis and in vitro anticancer activities of substituted N-(4′-nitrophenyl)-l-prolinamides
title_sort synthesis and in vitro anticancer activities of substituted n-(4′-nitrophenyl)-l-prolinamides
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7540745/
https://www.ncbi.nlm.nih.gov/pubmed/33047051
http://dx.doi.org/10.1098/rsos.200906
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