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Synthesis, Cytotoxic, and Computational Screening of Some Novel Indole–1,2,4-Triazole-Based S-Alkylated N-Aryl Acetamides
Molecular hybridization has emerged as the prime and most significant approach for the development of novel anticancer chemotherapeutic agents for combating cancer. In this pursuit, a novel series of indole–1,2,4-triazol-based N-phenyl acetamide structural motifs 8a–f were synthesized and screened a...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10669176/ https://www.ncbi.nlm.nih.gov/pubmed/38002078 http://dx.doi.org/10.3390/biomedicines11113078 |
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author | Zahoor, Ameer Fawad Saeed, Sadaf Rasul, Azhar Noreen, Razia Irfan, Ali Ahmad, Sajjad Faisal, Shah Al-Hussain, Sami A. Saeed, Muhammad Athar Muhammed, Muhammed Tilahun Muhammad, Zeinab A. Zaki, Magdi E. A. |
author_facet | Zahoor, Ameer Fawad Saeed, Sadaf Rasul, Azhar Noreen, Razia Irfan, Ali Ahmad, Sajjad Faisal, Shah Al-Hussain, Sami A. Saeed, Muhammad Athar Muhammed, Muhammed Tilahun Muhammad, Zeinab A. Zaki, Magdi E. A. |
author_sort | Zahoor, Ameer Fawad |
collection | PubMed |
description | Molecular hybridization has emerged as the prime and most significant approach for the development of novel anticancer chemotherapeutic agents for combating cancer. In this pursuit, a novel series of indole–1,2,4-triazol-based N-phenyl acetamide structural motifs 8a–f were synthesized and screened against the in vitro hepatocellular cancer Hep-G2 cell line. The MTT assay was applied to determine the anti-proliferative potential of novel indole–triazole compounds 8a–f, which displayed cytotoxicity potential as cell viabilities at 100 µg/mL concentration, by using ellipticine and doxorubicin as standard reference drugs. The remarkable prominent bioactive structural hybrids 8a, 8c, and 8f demonstrated good-to-excellent anti-Hep-G2 cancer chemotherapeutic potential, with a cell viability of (11.72 ± 0.53), (18.92 ± 1.48), and (12.93 ± 0.55), respectively. The excellent cytotoxicity efficacy against the liver cancer cell line Hep-G2 was displayed by the 3,4-dichloro moiety containing indole–triazole scaffold 8b, which had the lowest cell viability (10.99 ± 0.59) compared with the standard drug ellipticine (cell viability = 11.5 ± 0.55) but displayed comparable potency in comparison with the standard drug doxorubicin (cell viability = 10.8 ± 0.41). The structure–activity relationship (SAR) of indole–triazoles 8a–f revealed that the 3,4-dichlorophenyl-based indole–triazole structural hybrid 8b displayed excellent anti-Hep-G2 cancer chemotherapeutic efficacy. The in silico approaches such as molecular docking scores, molecular dynamic simulation stability data, DFT, ADMET studies, and in vitro pharmacological profile clearly indicated that indole–triazole scaffold 8b could be the lead anti-Hep-G2 liver cancer therapeutic agent and a promising anti-Hep-G2 drug candidate for further clinical evaluations. |
format | Online Article Text |
id | pubmed-10669176 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-106691762023-11-16 Synthesis, Cytotoxic, and Computational Screening of Some Novel Indole–1,2,4-Triazole-Based S-Alkylated N-Aryl Acetamides Zahoor, Ameer Fawad Saeed, Sadaf Rasul, Azhar Noreen, Razia Irfan, Ali Ahmad, Sajjad Faisal, Shah Al-Hussain, Sami A. Saeed, Muhammad Athar Muhammed, Muhammed Tilahun Muhammad, Zeinab A. Zaki, Magdi E. A. Biomedicines Article Molecular hybridization has emerged as the prime and most significant approach for the development of novel anticancer chemotherapeutic agents for combating cancer. In this pursuit, a novel series of indole–1,2,4-triazol-based N-phenyl acetamide structural motifs 8a–f were synthesized and screened against the in vitro hepatocellular cancer Hep-G2 cell line. The MTT assay was applied to determine the anti-proliferative potential of novel indole–triazole compounds 8a–f, which displayed cytotoxicity potential as cell viabilities at 100 µg/mL concentration, by using ellipticine and doxorubicin as standard reference drugs. The remarkable prominent bioactive structural hybrids 8a, 8c, and 8f demonstrated good-to-excellent anti-Hep-G2 cancer chemotherapeutic potential, with a cell viability of (11.72 ± 0.53), (18.92 ± 1.48), and (12.93 ± 0.55), respectively. The excellent cytotoxicity efficacy against the liver cancer cell line Hep-G2 was displayed by the 3,4-dichloro moiety containing indole–triazole scaffold 8b, which had the lowest cell viability (10.99 ± 0.59) compared with the standard drug ellipticine (cell viability = 11.5 ± 0.55) but displayed comparable potency in comparison with the standard drug doxorubicin (cell viability = 10.8 ± 0.41). The structure–activity relationship (SAR) of indole–triazoles 8a–f revealed that the 3,4-dichlorophenyl-based indole–triazole structural hybrid 8b displayed excellent anti-Hep-G2 cancer chemotherapeutic efficacy. The in silico approaches such as molecular docking scores, molecular dynamic simulation stability data, DFT, ADMET studies, and in vitro pharmacological profile clearly indicated that indole–triazole scaffold 8b could be the lead anti-Hep-G2 liver cancer therapeutic agent and a promising anti-Hep-G2 drug candidate for further clinical evaluations. MDPI 2023-11-16 /pmc/articles/PMC10669176/ /pubmed/38002078 http://dx.doi.org/10.3390/biomedicines11113078 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Zahoor, Ameer Fawad Saeed, Sadaf Rasul, Azhar Noreen, Razia Irfan, Ali Ahmad, Sajjad Faisal, Shah Al-Hussain, Sami A. Saeed, Muhammad Athar Muhammed, Muhammed Tilahun Muhammad, Zeinab A. Zaki, Magdi E. A. Synthesis, Cytotoxic, and Computational Screening of Some Novel Indole–1,2,4-Triazole-Based S-Alkylated N-Aryl Acetamides |
title | Synthesis, Cytotoxic, and Computational Screening of Some Novel Indole–1,2,4-Triazole-Based S-Alkylated N-Aryl Acetamides |
title_full | Synthesis, Cytotoxic, and Computational Screening of Some Novel Indole–1,2,4-Triazole-Based S-Alkylated N-Aryl Acetamides |
title_fullStr | Synthesis, Cytotoxic, and Computational Screening of Some Novel Indole–1,2,4-Triazole-Based S-Alkylated N-Aryl Acetamides |
title_full_unstemmed | Synthesis, Cytotoxic, and Computational Screening of Some Novel Indole–1,2,4-Triazole-Based S-Alkylated N-Aryl Acetamides |
title_short | Synthesis, Cytotoxic, and Computational Screening of Some Novel Indole–1,2,4-Triazole-Based S-Alkylated N-Aryl Acetamides |
title_sort | synthesis, cytotoxic, and computational screening of some novel indole–1,2,4-triazole-based s-alkylated n-aryl acetamides |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10669176/ https://www.ncbi.nlm.nih.gov/pubmed/38002078 http://dx.doi.org/10.3390/biomedicines11113078 |
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