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Synthesis and biological activity of fused tetracyclic Pyrrolo[2,1-c][1,4]benzodiazepines
Cancer remains the second major cause of death in the world. Thus, there is a pressing need to identify potential synthetic route for the development of novel anticancer agents which will serve as lead compounds to effectively combat this life-threatening epidemic. Pyrrolo[2,1-c][1,4]benzodiazepines...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5857631/ https://www.ncbi.nlm.nih.gov/pubmed/29560454 http://dx.doi.org/10.1016/j.heliyon.2018.e00539 |
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author | Annor-Gyamfi, Joel K. Jarrett, John M. Osazee, Joseph O. Bialonska, Dobrusia Whitted, Crystal Palau, Victoria E. Shilabin, Abbas G. |
author_facet | Annor-Gyamfi, Joel K. Jarrett, John M. Osazee, Joseph O. Bialonska, Dobrusia Whitted, Crystal Palau, Victoria E. Shilabin, Abbas G. |
author_sort | Annor-Gyamfi, Joel K. |
collection | PubMed |
description | Cancer remains the second major cause of death in the world. Thus, there is a pressing need to identify potential synthetic route for the development of novel anticancer agents which will serve as lead compounds to effectively combat this life-threatening epidemic. Pyrrolo[2,1-c][1,4]benzodiazepines (PBDs) have sparked a great interest as lead compounds because of their cancerostatic and anti-infective properties. The twisted molecular structure of PBD analogs provides both helical and chiral elements. In an effort to expand novel PBDs that interact with the key exocyclic amino group of the DNA-guanine base, we hypothesized that construction of a fused cyclic active system, would likely serve as an electrophilic site when compared to traditional electrophilic C11-N10 imine group. To examine our theory, we report herein the synthesis and cell viability/cytotoxicity of a series of PBD analogs using NCI-60 cell lines screening. Thus, compounds 1–13 were synthesized and fully characterized. The selected PBDs were found to have marginal inhibition of growth, up to 30%, for certain cell lines. |
format | Online Article Text |
id | pubmed-5857631 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-58576312018-03-20 Synthesis and biological activity of fused tetracyclic Pyrrolo[2,1-c][1,4]benzodiazepines Annor-Gyamfi, Joel K. Jarrett, John M. Osazee, Joseph O. Bialonska, Dobrusia Whitted, Crystal Palau, Victoria E. Shilabin, Abbas G. Heliyon Article Cancer remains the second major cause of death in the world. Thus, there is a pressing need to identify potential synthetic route for the development of novel anticancer agents which will serve as lead compounds to effectively combat this life-threatening epidemic. Pyrrolo[2,1-c][1,4]benzodiazepines (PBDs) have sparked a great interest as lead compounds because of their cancerostatic and anti-infective properties. The twisted molecular structure of PBD analogs provides both helical and chiral elements. In an effort to expand novel PBDs that interact with the key exocyclic amino group of the DNA-guanine base, we hypothesized that construction of a fused cyclic active system, would likely serve as an electrophilic site when compared to traditional electrophilic C11-N10 imine group. To examine our theory, we report herein the synthesis and cell viability/cytotoxicity of a series of PBD analogs using NCI-60 cell lines screening. Thus, compounds 1–13 were synthesized and fully characterized. The selected PBDs were found to have marginal inhibition of growth, up to 30%, for certain cell lines. Elsevier 2018-03-01 /pmc/articles/PMC5857631/ /pubmed/29560454 http://dx.doi.org/10.1016/j.heliyon.2018.e00539 Text en © 2018 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Annor-Gyamfi, Joel K. Jarrett, John M. Osazee, Joseph O. Bialonska, Dobrusia Whitted, Crystal Palau, Victoria E. Shilabin, Abbas G. Synthesis and biological activity of fused tetracyclic Pyrrolo[2,1-c][1,4]benzodiazepines |
title | Synthesis and biological activity of fused tetracyclic Pyrrolo[2,1-c][1,4]benzodiazepines |
title_full | Synthesis and biological activity of fused tetracyclic Pyrrolo[2,1-c][1,4]benzodiazepines |
title_fullStr | Synthesis and biological activity of fused tetracyclic Pyrrolo[2,1-c][1,4]benzodiazepines |
title_full_unstemmed | Synthesis and biological activity of fused tetracyclic Pyrrolo[2,1-c][1,4]benzodiazepines |
title_short | Synthesis and biological activity of fused tetracyclic Pyrrolo[2,1-c][1,4]benzodiazepines |
title_sort | synthesis and biological activity of fused tetracyclic pyrrolo[2,1-c][1,4]benzodiazepines |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5857631/ https://www.ncbi.nlm.nih.gov/pubmed/29560454 http://dx.doi.org/10.1016/j.heliyon.2018.e00539 |
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