Synthesis of 1H-1,2,3-Triazole-Linked Quinoline-Isatin Molecular Hybrids as Anti-Breast Cancer and Anti-Methicillin-Resistant Staphylococcus aureus (MRSA) Agents.
Anti-Bacterial Agents
/ chemical synthesis
Antineoplastic Agents
/ chemical synthesis
Breast Neoplasms
/ drug therapy
Cell Proliferation
/ drug effects
Cell Survival
/ drug effects
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Female
Humans
Isatin
/ chemistry
MCF-7 Cells
Methicillin-Resistant Staphylococcus aureus
/ drug effects
Microbial Sensitivity Tests
Molecular Structure
Quinolines
/ chemistry
Structure-Activity Relationship
Triazoles
/ chemistry
Breast cancer
in silico
isatin
methicillin-resistant Staphylococcus aureus
molecular hybridisation
quinoline
Journal
Anti-cancer agents in medicinal chemistry
ISSN: 1875-5992
Titre abrégé: Anticancer Agents Med Chem
Pays: Netherlands
ID NLM: 101265649
Informations de publication
Date de publication:
2021
2021
Historique:
received:
31
03
2020
revised:
10
08
2020
accepted:
23
08
2020
pubmed:
30
9
2020
medline:
11
1
2022
entrez:
29
9
2020
Statut:
ppublish
Résumé
The persistence of breast cancer as the leading cause of mortality among women, coupled with drug resistance to tamoxifen, the standard endocrine therapy for the disease, exacts continuous attention. To this effect, molecular hybridisation offers an attractive route to drugs with improved bioactivity profiles. The primary goal of this study was to examine the potential of 1H-1,2,3-triazole linked quinolineisatin molecular hybrids as drug candidates against breast cancer and Methicillin-Resistant Staphylococcus aureus (MRSA) cells. The quinoline-isatin hybrids were synthesised via click chemistry-mediated molecular hybridisation strategy. Anti-breast cancer activity was determined in 3-(4,5-dimethylthiazol-z-yl)-2,5-diphenyltetrazolium bromide (MTT) assay using Estrogen-Responsive (ER+) MCF-7 and MDA-MB-231 (Triple-Negative Breast Cancer -TNBC) cells, while antimicrobial efficacy was established via the broth dilution method. Also, the toxicity profile of potent compounds to non-cancerous cells was determined using human embryonic kidney cells (HEK293) and human Red Blood Cells (hRBCs). In silico techniques were employed to predict the druglike properties of potent compounds and understand their binding modes with Estrogen Receptor alpha (ERα). Compounds 7g-i exhibited the strongest cytotoxicity to MCF-7 cells with IC These results suggest that the identified 1H-1,2,3-triazole-linked quinoline-isatin hybrids are viable chemotypes that can be adopted as templates for the development of new anti-breast cancer and anti-MRSA agents.
Sections du résumé
BACKGROUND
The persistence of breast cancer as the leading cause of mortality among women, coupled with drug resistance to tamoxifen, the standard endocrine therapy for the disease, exacts continuous attention. To this effect, molecular hybridisation offers an attractive route to drugs with improved bioactivity profiles.
OBJECTIVE
The primary goal of this study was to examine the potential of 1H-1,2,3-triazole linked quinolineisatin molecular hybrids as drug candidates against breast cancer and Methicillin-Resistant Staphylococcus aureus (MRSA) cells.
METHODS
The quinoline-isatin hybrids were synthesised via click chemistry-mediated molecular hybridisation strategy. Anti-breast cancer activity was determined in 3-(4,5-dimethylthiazol-z-yl)-2,5-diphenyltetrazolium bromide (MTT) assay using Estrogen-Responsive (ER+) MCF-7 and MDA-MB-231 (Triple-Negative Breast Cancer -TNBC) cells, while antimicrobial efficacy was established via the broth dilution method. Also, the toxicity profile of potent compounds to non-cancerous cells was determined using human embryonic kidney cells (HEK293) and human Red Blood Cells (hRBCs). In silico techniques were employed to predict the druglike properties of potent compounds and understand their binding modes with Estrogen Receptor alpha (ERα).
RESULTS
Compounds 7g-i exhibited the strongest cytotoxicity to MCF-7 cells with IC
CONCLUSION
These results suggest that the identified 1H-1,2,3-triazole-linked quinoline-isatin hybrids are viable chemotypes that can be adopted as templates for the development of new anti-breast cancer and anti-MRSA agents.
Identifiants
pubmed: 32990543
pii: ACAMC-EPUB-110331
doi: 10.2174/1871520620666200929153138
doi:
Substances chimiques
Anti-Bacterial Agents
0
Antineoplastic Agents
0
Quinolines
0
Triazoles
0
Isatin
82X95S7M06
quinoline
E66400VT9R
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1228-1239Subventions
Organisme : National Research Foundation (NRF) South Africa
ID : 121276
Informations de copyright
Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.