Novel derivatives of nitro-substituted salicylic acids: Synthesis, antimicrobial activity and cytotoxicity

Georgios Paraskevopoulos; Martin Krátký; Jana Mandíková; František Trejtnar; Jiřina Stolaříková; Petr Pávek; Gurdyal Besra; Jarmila Vinšová

doi:10.1016/j.bmc.2015.10.029

Novel derivatives of nitro-substituted salicylic acids: Synthesis, antimicrobial activity and cytotoxicity

Georgios Paraskevopoulos, Martin Krátký, Jana Mandíková, František Trejtnar, Jiřina Stolaříková, Petr Pávek, Gurdyal Besra, Jarmila Vinšová

Biosciences

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Abstract

Inspired by the high antituberculous activity of novel nitro-substituted derivatives and based on promising predicted ADMET properties we have synthesized a series of 33 salicylanilides containing nitro-group in their salicylic part and evaluated them for their in vitro antimycobacterial, antimicrobial and antifungal activities. The presence of nitro-group in position 4 of the salicylic acid was found to be beneficial and the resulting molecules exhibited minimum inhibitory concentrations (MICs) ranging from 2 to 32μM against Mycobacterium tuberculosis. The best activity was found for 2-hydroxy-4-nitro-N-[4-(trifluoromethyl)phenyl]benzamide (MIC=2μM). 4-Nitrosalicylanilides were also found to be active against all Staphylococcus species tested while for MRSA strain 2-hydroxy-4-nitro-N-[4-(trifluoromethyl)phenyl]benzamide's MIC was 0.98μM. None of the nitrosalicylanilides was active against Enterococcus sp. J 14365/08 and no considerable activity was found against Gram-negative bacteria or fungi. The hepatotoxicity of all nitrosalicylanilides was found to be in the range of their MICs for HepG2 cells.

Original language	English
Pages (from-to)	7292-301
Number of pages	10
Journal	Bioorganic & Medicinal Chemistry
Volume	23
Issue number	22
Early online date	24 Oct 2015
DOIs	https://doi.org/10.1016/j.bmc.2015.10.029
Publication status	Published - 15 Nov 2015

Keywords

Salicylanilides
Nitro group
In silico ADMET prediction
In vitro antimycobacterial activity
Cytotoxicity

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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title = "Novel derivatives of nitro-substituted salicylic acids: Synthesis, antimicrobial activity and cytotoxicity",

abstract = "Inspired by the high antituberculous activity of novel nitro-substituted derivatives and based on promising predicted ADMET properties we have synthesized a series of 33 salicylanilides containing nitro-group in their salicylic part and evaluated them for their in vitro antimycobacterial, antimicrobial and antifungal activities. The presence of nitro-group in position 4 of the salicylic acid was found to be beneficial and the resulting molecules exhibited minimum inhibitory concentrations (MICs) ranging from 2 to 32μM against Mycobacterium tuberculosis. The best activity was found for 2-hydroxy-4-nitro-N-[4-(trifluoromethyl)phenyl]benzamide (MIC=2μM). 4-Nitrosalicylanilides were also found to be active against all Staphylococcus species tested while for MRSA strain 2-hydroxy-4-nitro-N-[4-(trifluoromethyl)phenyl]benzamide's MIC was 0.98μM. None of the nitrosalicylanilides was active against Enterococcus sp. J 14365/08 and no considerable activity was found against Gram-negative bacteria or fungi. The hepatotoxicity of all nitrosalicylanilides was found to be in the range of their MICs for HepG2 cells.",

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author = "Georgios Paraskevopoulos and Martin Kr{\'a}tk{\'y} and Jana Mand{\'i}kov{\'a} and Franti{\v s}ek Trejtnar and Ji{\v r}ina Stola{\v r}{\'i}kov{\'a} and Petr P{\'a}vek and Gurdyal Besra and Jarmila Vin{\v s}ov{\'a}",

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doi = "10.1016/j.bmc.2015.10.029",

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T1 - Novel derivatives of nitro-substituted salicylic acids

T2 - Synthesis, antimicrobial activity and cytotoxicity

AU - Paraskevopoulos, Georgios

AU - Krátký, Martin

AU - Mandíková, Jana

AU - Trejtnar, František

AU - Stolaříková, Jiřina

AU - Pávek, Petr

AU - Besra, Gurdyal

AU - Vinšová, Jarmila

PY - 2015/11/15

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N2 - Inspired by the high antituberculous activity of novel nitro-substituted derivatives and based on promising predicted ADMET properties we have synthesized a series of 33 salicylanilides containing nitro-group in their salicylic part and evaluated them for their in vitro antimycobacterial, antimicrobial and antifungal activities. The presence of nitro-group in position 4 of the salicylic acid was found to be beneficial and the resulting molecules exhibited minimum inhibitory concentrations (MICs) ranging from 2 to 32μM against Mycobacterium tuberculosis. The best activity was found for 2-hydroxy-4-nitro-N-[4-(trifluoromethyl)phenyl]benzamide (MIC=2μM). 4-Nitrosalicylanilides were also found to be active against all Staphylococcus species tested while for MRSA strain 2-hydroxy-4-nitro-N-[4-(trifluoromethyl)phenyl]benzamide's MIC was 0.98μM. None of the nitrosalicylanilides was active against Enterococcus sp. J 14365/08 and no considerable activity was found against Gram-negative bacteria or fungi. The hepatotoxicity of all nitrosalicylanilides was found to be in the range of their MICs for HepG2 cells.

AB - Inspired by the high antituberculous activity of novel nitro-substituted derivatives and based on promising predicted ADMET properties we have synthesized a series of 33 salicylanilides containing nitro-group in their salicylic part and evaluated them for their in vitro antimycobacterial, antimicrobial and antifungal activities. The presence of nitro-group in position 4 of the salicylic acid was found to be beneficial and the resulting molecules exhibited minimum inhibitory concentrations (MICs) ranging from 2 to 32μM against Mycobacterium tuberculosis. The best activity was found for 2-hydroxy-4-nitro-N-[4-(trifluoromethyl)phenyl]benzamide (MIC=2μM). 4-Nitrosalicylanilides were also found to be active against all Staphylococcus species tested while for MRSA strain 2-hydroxy-4-nitro-N-[4-(trifluoromethyl)phenyl]benzamide's MIC was 0.98μM. None of the nitrosalicylanilides was active against Enterococcus sp. J 14365/08 and no considerable activity was found against Gram-negative bacteria or fungi. The hepatotoxicity of all nitrosalicylanilides was found to be in the range of their MICs for HepG2 cells.

KW - Salicylanilides

KW - Nitro group

KW - In silico ADMET prediction

KW - In vitro antimycobacterial activity

KW - Cytotoxicity

U2 - 10.1016/j.bmc.2015.10.029

DO - 10.1016/j.bmc.2015.10.029

M3 - Article

C2 - 26526729

SN - 0968-0896

VL - 23

SP - 7292

EP - 7301

JO - Bioorganic & Medicinal Chemistry

JF - Bioorganic & Medicinal Chemistry

IS - 22

ER -

Novel derivatives of nitro-substituted salicylic acids: Synthesis, antimicrobial activity and cytotoxicity

Abstract

Keywords

UN SDGs

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