Design, synthesis, antibacterial activity evaluation and molecular modeling studies of new sulfonamides containing a sulfathiazole moiety
Nema prikaza
Autori
Meseli, TugbaDogan, Sengul Dilem
Gunduz, Miyase Gozde
Kokbudak, Zulbiye
Škaro Bogojević, Sanja
Noonan, Theresa
Vojnović, Sandra
Wolber, Gerhard
Nikodinović-Runić, Jasmina
Članak u časopisu (Objavljena verzija)
Metapodaci
Prikaz svih podataka o dokumentuApstrakt
Sulfonamides represent the oldest synthetic antibacterial agents; however, their central position in controlling bacterial diseases has been seriously damaged by the development of widespread resistance. Herein, we revisited sulfathiazole, a commercial member of antibacterial sulfa drugs, intending to overcome sulfonamide resistance and identify new drug candidates through molecular modifications. We synthesized twelve sulfonamides (SA1-SA12) by replacing the amino group on the phenyl ring with various substituents and introducing a thiophene ring on the core scaffold of sulfathiazole. The obtained compounds and additionally two commercial sulfonamides, sulfathiazole and sulfadiazine, were extensively screened for their antimicrobial activities. The results indicated that new sulfonamides, unlike traditional ones, were selectively effective against various Staphylococcus aureus strains. Introducing a bulky lipophilic substituent at the para position of the phenyl ring significantly inc...reased the antibacterial activities of the compounds against Staphylococcus aureus. The compounds demonstrating favourable selectivity indices were further evaluated for their membrane potential perturbation and DNA interaction properties. The obtained data showed that these are not supporting mechanisms for the antibacterial activities of the modified sulfathiazole derivatives. In order to rationalize the activity of the three most active compounds, SA7, SA11 and SA12, against S. aureus ATCC 25923, their binding hypotheses within the catalytic site of Staphylococcus aureus dihydropteroate synthase, the validated target enzyme of sulfonamides, were generated via molecular docking and further dissected using molecular dynamics simulations and dynamic 3D pharmacophores (dynophores).
Izvor:
New Journal of Chemistry, 2021, 45, 18, 8166-8177Izdavač:
- Royal Soc Chemistry, Cambridge
Finansiranje / projekti:
- Research Foundation of Erciyes University [FBA-2017-7340]
- Sonnenfeld Foundation
- Ministarstvo nauke, tehnološkog razvoja i inovacija Republike Srbije, institucionalno finansiranje - 200042 (Univerzitet u Beogradu, Institut za molekularnu genetiku i genetičko inženjerstvo) (RS-MESTD-inst-2020-200042)
DOI: 10.1039/d1nj00150g
ISSN: 1144-0546
WoS: 000641873300001
Scopus: 2-s2.0-85105866791
Institucija/grupa
Institut za molekularnu genetiku i genetičko inženjerstvoTY - JOUR AU - Meseli, Tugba AU - Dogan, Sengul Dilem AU - Gunduz, Miyase Gozde AU - Kokbudak, Zulbiye AU - Škaro Bogojević, Sanja AU - Noonan, Theresa AU - Vojnović, Sandra AU - Wolber, Gerhard AU - Nikodinović-Runić, Jasmina PY - 2021 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/1417 AB - Sulfonamides represent the oldest synthetic antibacterial agents; however, their central position in controlling bacterial diseases has been seriously damaged by the development of widespread resistance. Herein, we revisited sulfathiazole, a commercial member of antibacterial sulfa drugs, intending to overcome sulfonamide resistance and identify new drug candidates through molecular modifications. We synthesized twelve sulfonamides (SA1-SA12) by replacing the amino group on the phenyl ring with various substituents and introducing a thiophene ring on the core scaffold of sulfathiazole. The obtained compounds and additionally two commercial sulfonamides, sulfathiazole and sulfadiazine, were extensively screened for their antimicrobial activities. The results indicated that new sulfonamides, unlike traditional ones, were selectively effective against various Staphylococcus aureus strains. Introducing a bulky lipophilic substituent at the para position of the phenyl ring significantly increased the antibacterial activities of the compounds against Staphylococcus aureus. The compounds demonstrating favourable selectivity indices were further evaluated for their membrane potential perturbation and DNA interaction properties. The obtained data showed that these are not supporting mechanisms for the antibacterial activities of the modified sulfathiazole derivatives. In order to rationalize the activity of the three most active compounds, SA7, SA11 and SA12, against S. aureus ATCC 25923, their binding hypotheses within the catalytic site of Staphylococcus aureus dihydropteroate synthase, the validated target enzyme of sulfonamides, were generated via molecular docking and further dissected using molecular dynamics simulations and dynamic 3D pharmacophores (dynophores). PB - Royal Soc Chemistry, Cambridge T2 - New Journal of Chemistry T1 - Design, synthesis, antibacterial activity evaluation and molecular modeling studies of new sulfonamides containing a sulfathiazole moiety EP - 8177 IS - 18 SP - 8166 VL - 45 DO - 10.1039/d1nj00150g ER -
@article{ author = "Meseli, Tugba and Dogan, Sengul Dilem and Gunduz, Miyase Gozde and Kokbudak, Zulbiye and Škaro Bogojević, Sanja and Noonan, Theresa and Vojnović, Sandra and Wolber, Gerhard and Nikodinović-Runić, Jasmina", year = "2021", abstract = "Sulfonamides represent the oldest synthetic antibacterial agents; however, their central position in controlling bacterial diseases has been seriously damaged by the development of widespread resistance. Herein, we revisited sulfathiazole, a commercial member of antibacterial sulfa drugs, intending to overcome sulfonamide resistance and identify new drug candidates through molecular modifications. We synthesized twelve sulfonamides (SA1-SA12) by replacing the amino group on the phenyl ring with various substituents and introducing a thiophene ring on the core scaffold of sulfathiazole. The obtained compounds and additionally two commercial sulfonamides, sulfathiazole and sulfadiazine, were extensively screened for their antimicrobial activities. The results indicated that new sulfonamides, unlike traditional ones, were selectively effective against various Staphylococcus aureus strains. Introducing a bulky lipophilic substituent at the para position of the phenyl ring significantly increased the antibacterial activities of the compounds against Staphylococcus aureus. The compounds demonstrating favourable selectivity indices were further evaluated for their membrane potential perturbation and DNA interaction properties. The obtained data showed that these are not supporting mechanisms for the antibacterial activities of the modified sulfathiazole derivatives. In order to rationalize the activity of the three most active compounds, SA7, SA11 and SA12, against S. aureus ATCC 25923, their binding hypotheses within the catalytic site of Staphylococcus aureus dihydropteroate synthase, the validated target enzyme of sulfonamides, were generated via molecular docking and further dissected using molecular dynamics simulations and dynamic 3D pharmacophores (dynophores).", publisher = "Royal Soc Chemistry, Cambridge", journal = "New Journal of Chemistry", title = "Design, synthesis, antibacterial activity evaluation and molecular modeling studies of new sulfonamides containing a sulfathiazole moiety", pages = "8177-8166", number = "18", volume = "45", doi = "10.1039/d1nj00150g" }
Meseli, T., Dogan, S. D., Gunduz, M. G., Kokbudak, Z., Škaro Bogojević, S., Noonan, T., Vojnović, S., Wolber, G.,& Nikodinović-Runić, J.. (2021). Design, synthesis, antibacterial activity evaluation and molecular modeling studies of new sulfonamides containing a sulfathiazole moiety. in New Journal of Chemistry Royal Soc Chemistry, Cambridge., 45(18), 8166-8177. https://doi.org/10.1039/d1nj00150g
Meseli T, Dogan SD, Gunduz MG, Kokbudak Z, Škaro Bogojević S, Noonan T, Vojnović S, Wolber G, Nikodinović-Runić J. Design, synthesis, antibacterial activity evaluation and molecular modeling studies of new sulfonamides containing a sulfathiazole moiety. in New Journal of Chemistry. 2021;45(18):8166-8177. doi:10.1039/d1nj00150g .
Meseli, Tugba, Dogan, Sengul Dilem, Gunduz, Miyase Gozde, Kokbudak, Zulbiye, Škaro Bogojević, Sanja, Noonan, Theresa, Vojnović, Sandra, Wolber, Gerhard, Nikodinović-Runić, Jasmina, "Design, synthesis, antibacterial activity evaluation and molecular modeling studies of new sulfonamides containing a sulfathiazole moiety" in New Journal of Chemistry, 45, no. 18 (2021):8166-8177, https://doi.org/10.1039/d1nj00150g . .