N-Derivatives of (Z)-Methyl 3-(4-Oxo-2-thioxothiazolidin-5-ylidene)methyl)-1H-indole-2-carboxylates as Antimicrobial Agents-In Silico and In Vitro Evaluation
2023
Authors:
Petrou, AnthiGeronikaki, Athina
Kartsev, Victor
Kousaxidis, Antonios
Papadimitriou-Tsantarliotou, Aliki
Kostić, Marina
Ivanov, Marija
Soković, Marina
Nicolaou, Ioannis
Vizirianakis, Ioannis S.
Document Type:
Article (Published version)
Metadata
Show full item recordAbstract:
Herein, we report the experimental evaluation of the antimicrobial activity of seventeen new (Z)-methyl 3-(4-oxo-2-thioxothiazolidin-5-ylidene)methyl)-1H-indole-2-carboxylate derivatives. All tested compounds exhibited antibacterial activity against eight Gram-positive and Gram-negative bacteria. Their activity exceeded those of ampicillin as well as streptomycin by 10-50 fold. The most sensitive bacterium was En. Cloacae, while E. coli was the most resistant one, followed by M. flavus. The most active compound appeared to be compound 8 with MIC at 0.004-0.03 mg/mL and MBC at 0.008-0.06 mg/mL. The antifungal activity of tested compounds was good to excellent with MIC in the range of 0.004-0.06 mg/mL, with compound 15 being the most potent. T. viride was the most sensitive fungal, while A. fumigatus was the most resistant one. Docking studies revealed that the inhibition of E. coli MurB is probably responsible for their antibacterial activity, while 14a-lanosterol demethylase of CYP51Ca is involved in the mechanism of antifungal activity. Furthermore, drug-likeness and ADMET profile prediction were performed. Finally, the cytotoxicity studies were performed for the most active compounds using MTT assay against normal MRC5 cells.
Keywords:
ADMET; antibacterial activity; antifungal activity; antimicrobial; cytotoxicity; indole; molecular docking; rhodanineSource:
Pharmaceuticals, 2023, 16, 1, 131-Funding / projects:
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200007 (University of Belgrade, Institute for Biological Research 'Siniša Stanković') (RS-MESTD-inst-2020-200007)
DOI: 10.3390/ph16010131
ISSN: 1424-8247
PubMed: 36678628
WoS: 000918911300001
Scopus: 2-s2.0-85146812650
URI
https://www.mdpi.com/1424-8247/16/1/131http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC9865890
http://radar.ibiss.bg.ac.rs/handle/123456789/5459