In Search of New Drugs: Elucidating the Activity of Structurally Similar Potential Antibiotics Using Molecular Modelling

The global problem of antibiotic resistance leads to the necessity for drug improvement and discovery. Natural and synthetic sulfur-containing compounds have been known as antibiotics for many years. In the current study, we demonstrated an antibacterial activity of three new thiosulfonates: S-ethyl...

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Main Authors: Natalina Makieieva, Teobald Kupka, Piotr Lodowski, Radosław Balwierz, Katarzyna Kasperkiewicz, Adam Byrski, Roksolana Konechna, Vira Lubenets
Format: Article
Language:English
Published: MDPI AG 2025-07-01
Series:Molecules
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Online Access:https://www.mdpi.com/1420-3049/30/14/2920
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author Natalina Makieieva
Teobald Kupka
Piotr Lodowski
Radosław Balwierz
Katarzyna Kasperkiewicz
Adam Byrski
Roksolana Konechna
Vira Lubenets
author_facet Natalina Makieieva
Teobald Kupka
Piotr Lodowski
Radosław Balwierz
Katarzyna Kasperkiewicz
Adam Byrski
Roksolana Konechna
Vira Lubenets
author_sort Natalina Makieieva
collection DOAJ
description The global problem of antibiotic resistance leads to the necessity for drug improvement and discovery. Natural and synthetic sulfur-containing compounds have been known as antibiotics for many years. In the current study, we demonstrated an antibacterial activity of three new thiosulfonates: S-ethyl 4-aminobenzene-1-sulfonothioate (1), S-methyl 4-acetamidobenzene-1-sulfonothioate (2), and S-ethyl 4-acetamidobenzene-1-sulfonothioate (3). Their activities were studied on two model Gram-positive and Gram-negative bacteria strains: <i>Staphylococcus aureus</i> ATTC 6538P and <i>Escherichia coli</i> ATTC 8739, respectively. According to the literature data, we proposed a general mechanism of 1−3 biochemical actions. To analyze its feasibility, theoretical studies using density functional theory (DFT) were performed. The obtained results demonstrate a direct correlation between some NBO parameters and the S-S bond energy of 1−3 with their activity against both studied bacterial strains. The obtained results could be helpful for future biomedical studies on the analyzed compounds and promote the further design of new S-containing antibiotics.
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spelling doaj-art-c429617ffb274dff9fc7f3be90bf54cb2025-08-20T03:56:49ZengMDPI AGMolecules1420-30492025-07-013014292010.3390/molecules30142920In Search of New Drugs: Elucidating the Activity of Structurally Similar Potential Antibiotics Using Molecular ModellingNatalina Makieieva0Teobald Kupka1Piotr Lodowski2Radosław Balwierz3Katarzyna Kasperkiewicz4Adam Byrski5Roksolana Konechna6Vira Lubenets7Faculty of Chemistry and Pharmacy, University of Opole, Oleska 48, 45-052 Opole, PolandFaculty of Chemistry and Pharmacy, University of Opole, Oleska 48, 45-052 Opole, PolandInstitute of Chemistry, University of Silesia in Katowice, Szkolna 9, 40-006 Katowice, PolandFaculty of Chemistry and Pharmacy, University of Opole, Oleska 48, 45-052 Opole, PolandFaculty of Natural Sciences, Institute of Biology, Biotechnology and Environmental Protection, University of Silesia in Katowice, Jagiellonska 28, 40-032 Katowice, PolandInstitute of Metallurgy and Materials Science, Polish Academy of Sciences, Reymonta 25, 30-059 Cracow, PolandDepartment of Technology of Biologically Active Substances, Pharmacy and Biotechnology of Lviv Polytechnic National University, S. Bandery 12, 79000 Lviv, UkraineDepartment of Technology of Biologically Active Substances, Pharmacy and Biotechnology of Lviv Polytechnic National University, S. Bandery 12, 79000 Lviv, UkraineThe global problem of antibiotic resistance leads to the necessity for drug improvement and discovery. Natural and synthetic sulfur-containing compounds have been known as antibiotics for many years. In the current study, we demonstrated an antibacterial activity of three new thiosulfonates: S-ethyl 4-aminobenzene-1-sulfonothioate (1), S-methyl 4-acetamidobenzene-1-sulfonothioate (2), and S-ethyl 4-acetamidobenzene-1-sulfonothioate (3). Their activities were studied on two model Gram-positive and Gram-negative bacteria strains: <i>Staphylococcus aureus</i> ATTC 6538P and <i>Escherichia coli</i> ATTC 8739, respectively. According to the literature data, we proposed a general mechanism of 1−3 biochemical actions. To analyze its feasibility, theoretical studies using density functional theory (DFT) were performed. The obtained results demonstrate a direct correlation between some NBO parameters and the S-S bond energy of 1−3 with their activity against both studied bacterial strains. The obtained results could be helpful for future biomedical studies on the analyzed compounds and promote the further design of new S-containing antibiotics.https://www.mdpi.com/1420-3049/30/14/2920S-containing antibioticsDFTNBOstructure-activity relationship
spellingShingle Natalina Makieieva
Teobald Kupka
Piotr Lodowski
Radosław Balwierz
Katarzyna Kasperkiewicz
Adam Byrski
Roksolana Konechna
Vira Lubenets
In Search of New Drugs: Elucidating the Activity of Structurally Similar Potential Antibiotics Using Molecular Modelling
Molecules
S-containing antibiotics
DFT
NBO
structure-activity relationship
title In Search of New Drugs: Elucidating the Activity of Structurally Similar Potential Antibiotics Using Molecular Modelling
title_full In Search of New Drugs: Elucidating the Activity of Structurally Similar Potential Antibiotics Using Molecular Modelling
title_fullStr In Search of New Drugs: Elucidating the Activity of Structurally Similar Potential Antibiotics Using Molecular Modelling
title_full_unstemmed In Search of New Drugs: Elucidating the Activity of Structurally Similar Potential Antibiotics Using Molecular Modelling
title_short In Search of New Drugs: Elucidating the Activity of Structurally Similar Potential Antibiotics Using Molecular Modelling
title_sort in search of new drugs elucidating the activity of structurally similar potential antibiotics using molecular modelling
topic S-containing antibiotics
DFT
NBO
structure-activity relationship
url https://www.mdpi.com/1420-3049/30/14/2920
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