Nitrobenzoates and Nitrothiobenzoates with Activity against <i>M. tuberculosis</i>
Esters of weak acids have shown improved antimycobacterial activity over the corresponding free acids and nitro benzoates in particular have previously shown to have a very intriguing activity. To expand the potential of nitro-derivatives of benzoic acid as antimycobacterial drugs and explore the ef...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-04-01
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| Series: | Microorganisms |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-2607/11/4/969 |
| _version_ | 1797604274752978944 |
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| author | João P. Pais Olha Antoniuk Raquel Freire David Pires Emília Valente Elsa Anes Luis Constantino |
| author_facet | João P. Pais Olha Antoniuk Raquel Freire David Pires Emília Valente Elsa Anes Luis Constantino |
| author_sort | João P. Pais |
| collection | DOAJ |
| description | Esters of weak acids have shown improved antimycobacterial activity over the corresponding free acids and nitro benzoates in particular have previously shown to have a very intriguing activity. To expand the potential of nitro-derivatives of benzoic acid as antimycobacterial drugs and explore the effects of various structural features on the activity of these compounds, we have obtained a library of 64 derivatives containing esters and thioesters of benzoates and studied their activity against <i>M. tuberculosis</i>, the stability of the compounds, their activation by mycobacterial enzymes and the potential cytotoxicity against human monocytic THP-1 cell line. Our results showed that the most active compounds are those with an aromatic nitro substitution, with the 3,5-dinitro esters series being the most active. Also, the greater antitubercular activity for the nitro derivatives was shown to be unrelated to their pKa values or hydrolysis rates. Given the conventional relationship between nitro-containing substances and toxicity, one might anticipate that the great antimicrobial activity of nitro compounds would be associated with high toxicity; yet, we have not found such a relationship. The nitrobenzoate scaffold, particularly the 3,5-dinitrobenzoate scaffold, merits further investigation, because it has the potential to generate future antimycobacterial agents with improved activity. |
| first_indexed | 2024-03-11T04:44:07Z |
| format | Article |
| id | doaj.art-e5e70d8b639c473687d0022d608ac902 |
| institution | Directory Open Access Journal |
| issn | 2076-2607 |
| language | English |
| last_indexed | 2024-03-11T04:44:07Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Microorganisms |
| spelling | doaj.art-e5e70d8b639c473687d0022d608ac9022023-11-17T20:33:09ZengMDPI AGMicroorganisms2076-26072023-04-0111496910.3390/microorganisms11040969Nitrobenzoates and Nitrothiobenzoates with Activity against <i>M. tuberculosis</i>João P. Pais0Olha Antoniuk1Raquel Freire2David Pires3Emília Valente4Elsa Anes5Luis Constantino6Research Institute for Medicines (iMed.UL), Av. Prof. Gama Pinto, 1649-003 Lisboa, PortugalResearch Institute for Medicines (iMed.UL), Av. Prof. Gama Pinto, 1649-003 Lisboa, PortugalResearch Institute for Medicines (iMed.UL), Av. Prof. Gama Pinto, 1649-003 Lisboa, PortugalResearch Institute for Medicines (iMed.UL), Av. Prof. Gama Pinto, 1649-003 Lisboa, PortugalFaculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, PortugalResearch Institute for Medicines (iMed.UL), Av. Prof. Gama Pinto, 1649-003 Lisboa, PortugalResearch Institute for Medicines (iMed.UL), Av. Prof. Gama Pinto, 1649-003 Lisboa, PortugalEsters of weak acids have shown improved antimycobacterial activity over the corresponding free acids and nitro benzoates in particular have previously shown to have a very intriguing activity. To expand the potential of nitro-derivatives of benzoic acid as antimycobacterial drugs and explore the effects of various structural features on the activity of these compounds, we have obtained a library of 64 derivatives containing esters and thioesters of benzoates and studied their activity against <i>M. tuberculosis</i>, the stability of the compounds, their activation by mycobacterial enzymes and the potential cytotoxicity against human monocytic THP-1 cell line. Our results showed that the most active compounds are those with an aromatic nitro substitution, with the 3,5-dinitro esters series being the most active. Also, the greater antitubercular activity for the nitro derivatives was shown to be unrelated to their pKa values or hydrolysis rates. Given the conventional relationship between nitro-containing substances and toxicity, one might anticipate that the great antimicrobial activity of nitro compounds would be associated with high toxicity; yet, we have not found such a relationship. The nitrobenzoate scaffold, particularly the 3,5-dinitrobenzoate scaffold, merits further investigation, because it has the potential to generate future antimycobacterial agents with improved activity.https://www.mdpi.com/2076-2607/11/4/969benzoatesnitrobenzoatestuberculosisprodrugsesterasesmycobacteria |
| spellingShingle | João P. Pais Olha Antoniuk Raquel Freire David Pires Emília Valente Elsa Anes Luis Constantino Nitrobenzoates and Nitrothiobenzoates with Activity against <i>M. tuberculosis</i> Microorganisms benzoates nitrobenzoates tuberculosis prodrugs esterases mycobacteria |
| title | Nitrobenzoates and Nitrothiobenzoates with Activity against <i>M. tuberculosis</i> |
| title_full | Nitrobenzoates and Nitrothiobenzoates with Activity against <i>M. tuberculosis</i> |
| title_fullStr | Nitrobenzoates and Nitrothiobenzoates with Activity against <i>M. tuberculosis</i> |
| title_full_unstemmed | Nitrobenzoates and Nitrothiobenzoates with Activity against <i>M. tuberculosis</i> |
| title_short | Nitrobenzoates and Nitrothiobenzoates with Activity against <i>M. tuberculosis</i> |
| title_sort | nitrobenzoates and nitrothiobenzoates with activity against i m tuberculosis i |
| topic | benzoates nitrobenzoates tuberculosis prodrugs esterases mycobacteria |
| url | https://www.mdpi.com/2076-2607/11/4/969 |
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