Novel Benzylidenehydrazide-1,2,3-Triazole Conjugates as Antitubercular Agents: Synthesis and Molecular Docking.
Antineoplastic Agents
/ chemical synthesis
Antioxidants
/ chemical synthesis
Antitubercular Agents
/ chemical synthesis
Benzylidene Compounds
/ chemical synthesis
Biphenyl Compounds
/ antagonists & inhibitors
Cell Line, Tumor
Cell Proliferation
/ drug effects
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Humans
Microbial Sensitivity Tests
Molecular Docking Simulation
Molecular Structure
Mycobacterium
/ drug effects
Picrates
/ antagonists & inhibitors
Structure-Activity Relationship
Triazoles
/ chemical synthesis
1,2,3-Triazole
ADME
antioxidant
antitubercular
cytotoxicity
docking study.
Journal
Mini reviews in medicinal chemistry
ISSN: 1875-5607
Titre abrégé: Mini Rev Med Chem
Pays: Netherlands
ID NLM: 101094212
Informations de publication
Date de publication:
2019
2019
Historique:
received:
06
02
2017
revised:
24
10
2017
accepted:
13
11
2017
pubmed:
19
7
2018
medline:
2
11
2019
entrez:
19
7
2018
Statut:
ppublish
Résumé
Novel 1,2,3-triazole based benzylidenehydrazide derivatives were synthesized and evaluated for antitubercular activity against Mycobacterium tuberculosis (MTB) H37Ra, M. bovis BCG and cytotoxic activity. Most of the derivatives exhibited promising in vitro potency against MTB characterized by lower MIC values. Among all the synthesized derivatives, compound 6a and 6j were the most active against active and dormant MTB H37Ra, respectively. Compound 6d was significantly active against dormant and active M. bovis BCG. The structure activity relationship has been explored on the basis of anti-tubercular activity data. The active compounds were also tested against THP-1, A549 and Panc-1 cell lines and showed no significant cytotoxicity. Further, the synthesized compounds were found to have potential antioxidant with IC50 range = 11.19-56.64 µg/mL. The molecular docking study of synthesized compounds was performed against DprE1 enzyme of MTB to understand the binding interactions. Furthermore, synthesized compounds were also analysed for ADME properties and the potency of compounds indicated that, this series can be considered as a starting point for the developement of novel and more potent anti-tubercular agents in future.
Sections du résumé
BACKGROUND & OBJECTIVE
OBJECTIVE
Novel 1,2,3-triazole based benzylidenehydrazide derivatives were synthesized and evaluated for antitubercular activity against Mycobacterium tuberculosis (MTB) H37Ra, M. bovis BCG and cytotoxic activity. Most of the derivatives exhibited promising in vitro potency against MTB characterized by lower MIC values.
METHODS
METHODS
Among all the synthesized derivatives, compound 6a and 6j were the most active against active and dormant MTB H37Ra, respectively. Compound 6d was significantly active against dormant and active M. bovis BCG.
RESULTS
RESULTS
The structure activity relationship has been explored on the basis of anti-tubercular activity data. The active compounds were also tested against THP-1, A549 and Panc-1 cell lines and showed no significant cytotoxicity. Further, the synthesized compounds were found to have potential antioxidant with IC50 range = 11.19-56.64 µg/mL. The molecular docking study of synthesized compounds was performed against DprE1 enzyme of MTB to understand the binding interactions.
CONCLUSION
CONCLUSIONS
Furthermore, synthesized compounds were also analysed for ADME properties and the potency of compounds indicated that, this series can be considered as a starting point for the developement of novel and more potent anti-tubercular agents in future.
Identifiants
pubmed: 30019644
pii: MRMC-EPUB-91794
doi: 10.2174/1389557518666180718124858
doi:
Substances chimiques
Antineoplastic Agents
0
Antioxidants
0
Antitubercular Agents
0
Benzylidene Compounds
0
Biphenyl Compounds
0
Picrates
0
Triazoles
0
1,1-diphenyl-2-picrylhydrazyl
DFD3H4VGDH
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1178-1194Informations de copyright
Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.