Cargando…
Synthesis, Molecular Docking Studies and In Silico ADMET Screening of New Heterocycles Linked Thiazole Conjugates as Potent Anti-Hepatic Cancer Agents
Thiazoles are important scaffolds in organic chemistry. Biosynthesis of thiazoles is considered to be an excellent target for the design of novel classes of therapeutic agents. In this study, a new series of 2-ethylidenehydrazono-5-arylazothiazoles 5a–d and 2-ethylidenehydrazono-5-arylazo- thiazolon...
Autores principales: | , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8003218/ https://www.ncbi.nlm.nih.gov/pubmed/33803823 http://dx.doi.org/10.3390/molecules26061705 |
_version_ | 1783671637956100096 |
---|---|
author | Rashdan, Huda R. M. El-Naggar, Mohamed Abdelmonsef, Aboubakr H. |
author_facet | Rashdan, Huda R. M. El-Naggar, Mohamed Abdelmonsef, Aboubakr H. |
author_sort | Rashdan, Huda R. M. |
collection | PubMed |
description | Thiazoles are important scaffolds in organic chemistry. Biosynthesis of thiazoles is considered to be an excellent target for the design of novel classes of therapeutic agents. In this study, a new series of 2-ethylidenehydrazono-5-arylazothiazoles 5a–d and 2-ethylidenehydrazono-5-arylazo- thiazolones 8a–d were synthesized via the cyclocondensation reaction of the appropriate hydrazonyl halides 4a–d and 7a–d with ethylidene thiosemicarbazide 3, respectively. Furthermore, the thiosemicarbazide derivative 3 was reacted with different bromoacetyl compounds 10–12 to afford the respective thiazole derivatives 13–15. Chemical composition of the novel derivatives was established on bases of their spectral data (FTIR, (1)H-NMR, (13)C-NMR and mass spectrometry) and microanalytical data. The newly synthesized derivatives were screened for their in vitro anti-hepatic cancer potency using an MTT assay. Moreover, an in silico technique was used to assess the interaction modes of the compounds with the active site of Rho6 protein. The docking studies of the target Rho6 with the newly synthesized fourteen compounds showed good docking scores with acceptable binding interactions. The presented results revealed that the newly synthesized compounds exhibited promising inhibition activity against hepatic cancer cell lines (HepG2). |
format | Online Article Text |
id | pubmed-8003218 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-80032182021-03-28 Synthesis, Molecular Docking Studies and In Silico ADMET Screening of New Heterocycles Linked Thiazole Conjugates as Potent Anti-Hepatic Cancer Agents Rashdan, Huda R. M. El-Naggar, Mohamed Abdelmonsef, Aboubakr H. Molecules Article Thiazoles are important scaffolds in organic chemistry. Biosynthesis of thiazoles is considered to be an excellent target for the design of novel classes of therapeutic agents. In this study, a new series of 2-ethylidenehydrazono-5-arylazothiazoles 5a–d and 2-ethylidenehydrazono-5-arylazo- thiazolones 8a–d were synthesized via the cyclocondensation reaction of the appropriate hydrazonyl halides 4a–d and 7a–d with ethylidene thiosemicarbazide 3, respectively. Furthermore, the thiosemicarbazide derivative 3 was reacted with different bromoacetyl compounds 10–12 to afford the respective thiazole derivatives 13–15. Chemical composition of the novel derivatives was established on bases of their spectral data (FTIR, (1)H-NMR, (13)C-NMR and mass spectrometry) and microanalytical data. The newly synthesized derivatives were screened for their in vitro anti-hepatic cancer potency using an MTT assay. Moreover, an in silico technique was used to assess the interaction modes of the compounds with the active site of Rho6 protein. The docking studies of the target Rho6 with the newly synthesized fourteen compounds showed good docking scores with acceptable binding interactions. The presented results revealed that the newly synthesized compounds exhibited promising inhibition activity against hepatic cancer cell lines (HepG2). MDPI 2021-03-18 /pmc/articles/PMC8003218/ /pubmed/33803823 http://dx.doi.org/10.3390/molecules26061705 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Rashdan, Huda R. M. El-Naggar, Mohamed Abdelmonsef, Aboubakr H. Synthesis, Molecular Docking Studies and In Silico ADMET Screening of New Heterocycles Linked Thiazole Conjugates as Potent Anti-Hepatic Cancer Agents |
title | Synthesis, Molecular Docking Studies and In Silico ADMET Screening of New Heterocycles Linked Thiazole Conjugates as Potent Anti-Hepatic Cancer Agents |
title_full | Synthesis, Molecular Docking Studies and In Silico ADMET Screening of New Heterocycles Linked Thiazole Conjugates as Potent Anti-Hepatic Cancer Agents |
title_fullStr | Synthesis, Molecular Docking Studies and In Silico ADMET Screening of New Heterocycles Linked Thiazole Conjugates as Potent Anti-Hepatic Cancer Agents |
title_full_unstemmed | Synthesis, Molecular Docking Studies and In Silico ADMET Screening of New Heterocycles Linked Thiazole Conjugates as Potent Anti-Hepatic Cancer Agents |
title_short | Synthesis, Molecular Docking Studies and In Silico ADMET Screening of New Heterocycles Linked Thiazole Conjugates as Potent Anti-Hepatic Cancer Agents |
title_sort | synthesis, molecular docking studies and in silico admet screening of new heterocycles linked thiazole conjugates as potent anti-hepatic cancer agents |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8003218/ https://www.ncbi.nlm.nih.gov/pubmed/33803823 http://dx.doi.org/10.3390/molecules26061705 |
work_keys_str_mv | AT rashdanhudarm synthesismoleculardockingstudiesandinsilicoadmetscreeningofnewheterocycleslinkedthiazoleconjugatesaspotentantihepaticcanceragents AT elnaggarmohamed synthesismoleculardockingstudiesandinsilicoadmetscreeningofnewheterocycleslinkedthiazoleconjugatesaspotentantihepaticcanceragents AT abdelmonsefaboubakrh synthesismoleculardockingstudiesandinsilicoadmetscreeningofnewheterocycleslinkedthiazoleconjugatesaspotentantihepaticcanceragents |