Synthesis and anti-Candida activity of novel benzothiepino[3,2-c]pyridine derivatives
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2016
Authors
Božinović, Nina S.
Šegan, Sandra B.

Vojnović, Sandra

Pavić, Aleksandar

Šolaja, Bogdan A.

Nikodinović-Runić, Jasmina

Opsenica, Igor

Article (Published version)

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A novel series of thiepine derivatives were synthesized and evaluated as potential antimicrobials. All the synthesized compounds were evaluated for their antimicrobial activities in vitro against the fungi Candida albicans (ATCC 10231), C.parapsilosis (clinical isolate), Gram-negative bacterium Pseudomonas aeruginosa (ATCC 44752), and Gram-positive bacterium Staphylococcus aureus (ATCC 25923). Synthesized compounds showed higher antifungal activity than antibacterial activity, indicating that they could be used as selective antimicrobials. Selected thiepines efficiently inhibited Candida hyphae formation, a trait necessary for their pathogenicity. Thiepine 8-phenyl[1]benzothiepino[3,2-c]pyridine (16) efficiently killed Candida albicans at 15.6g/mL and showed no embryotoxicity at 75g/mL. Derivative 8-[4-(4,5-dihydro-1H-imidazol-2-yl)phenyl][1]benzothiepino[3,2-c]pyridine (23) caused significant hemolysis and in vitro DNA interaction. The position of the phenyl ring was essential for the... antifungal activity, while the electronic effects of the substituents did not significantly influence activity. Results obtained from in vivo embryotoxicity on zebrafish (Danio rerio) encourage further structure optimizations.
Keywords:
antifungal / Candida sp / Pd-catalyzed S-arylation / Thiepine / ZebrafishSource:
Chemical Biology and Drug Design, 2016, 88, 6, 795-806Publisher:
- Wiley, Hoboken
Funding / projects:
- The synthesis of aminoquinoline-based antimalarials and botulinum neurotoxin A inhibitors (RS-172008)
- Microbial diversity study and characterization of beneficial environmental microorganisms (RS-173048)
- Serbian Academy of Sciences and Arts
Note:
- Peer-reviewed manuscript: http://cherry.chem.bg.ac.rs/handle/123456789/3620
- Supplementary material: http://cherry.chem.bg.ac.rs/handle/123456789/3621
DOI: 10.1111/cbdd.12809
ISSN: 1747-0277
PubMed: 27316378
WoS: 000387362800002
Scopus: 2-s2.0-84978886752
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Hemijski fakultetTY - JOUR AU - Božinović, Nina S. AU - Šegan, Sandra B. AU - Vojnović, Sandra AU - Pavić, Aleksandar AU - Šolaja, Bogdan A. AU - Nikodinović-Runić, Jasmina AU - Opsenica, Igor PY - 2016 UR - https://cherry.chem.bg.ac.rs/handle/123456789/2346 AB - A novel series of thiepine derivatives were synthesized and evaluated as potential antimicrobials. All the synthesized compounds were evaluated for their antimicrobial activities in vitro against the fungi Candida albicans (ATCC 10231), C.parapsilosis (clinical isolate), Gram-negative bacterium Pseudomonas aeruginosa (ATCC 44752), and Gram-positive bacterium Staphylococcus aureus (ATCC 25923). Synthesized compounds showed higher antifungal activity than antibacterial activity, indicating that they could be used as selective antimicrobials. Selected thiepines efficiently inhibited Candida hyphae formation, a trait necessary for their pathogenicity. Thiepine 8-phenyl[1]benzothiepino[3,2-c]pyridine (16) efficiently killed Candida albicans at 15.6g/mL and showed no embryotoxicity at 75g/mL. Derivative 8-[4-(4,5-dihydro-1H-imidazol-2-yl)phenyl][1]benzothiepino[3,2-c]pyridine (23) caused significant hemolysis and in vitro DNA interaction. The position of the phenyl ring was essential for the antifungal activity, while the electronic effects of the substituents did not significantly influence activity. Results obtained from in vivo embryotoxicity on zebrafish (Danio rerio) encourage further structure optimizations. PB - Wiley, Hoboken T2 - Chemical Biology and Drug Design T1 - Synthesis and anti-Candida activity of novel benzothiepino[3,2-c]pyridine derivatives VL - 88 IS - 6 SP - 795 EP - 806 DO - 10.1111/cbdd.12809 ER -
@article{ author = "Božinović, Nina S. and Šegan, Sandra B. and Vojnović, Sandra and Pavić, Aleksandar and Šolaja, Bogdan A. and Nikodinović-Runić, Jasmina and Opsenica, Igor", year = "2016", abstract = "A novel series of thiepine derivatives were synthesized and evaluated as potential antimicrobials. All the synthesized compounds were evaluated for their antimicrobial activities in vitro against the fungi Candida albicans (ATCC 10231), C.parapsilosis (clinical isolate), Gram-negative bacterium Pseudomonas aeruginosa (ATCC 44752), and Gram-positive bacterium Staphylococcus aureus (ATCC 25923). Synthesized compounds showed higher antifungal activity than antibacterial activity, indicating that they could be used as selective antimicrobials. Selected thiepines efficiently inhibited Candida hyphae formation, a trait necessary for their pathogenicity. Thiepine 8-phenyl[1]benzothiepino[3,2-c]pyridine (16) efficiently killed Candida albicans at 15.6g/mL and showed no embryotoxicity at 75g/mL. Derivative 8-[4-(4,5-dihydro-1H-imidazol-2-yl)phenyl][1]benzothiepino[3,2-c]pyridine (23) caused significant hemolysis and in vitro DNA interaction. The position of the phenyl ring was essential for the antifungal activity, while the electronic effects of the substituents did not significantly influence activity. Results obtained from in vivo embryotoxicity on zebrafish (Danio rerio) encourage further structure optimizations.", publisher = "Wiley, Hoboken", journal = "Chemical Biology and Drug Design", title = "Synthesis and anti-Candida activity of novel benzothiepino[3,2-c]pyridine derivatives", volume = "88", number = "6", pages = "795-806", doi = "10.1111/cbdd.12809" }
Božinović, N. S., Šegan, S. B., Vojnović, S., Pavić, A., Šolaja, B. A., Nikodinović-Runić, J.,& Opsenica, I.. (2016). Synthesis and anti-Candida activity of novel benzothiepino[3,2-c]pyridine derivatives. in Chemical Biology and Drug Design Wiley, Hoboken., 88(6), 795-806. https://doi.org/10.1111/cbdd.12809
Božinović NS, Šegan SB, Vojnović S, Pavić A, Šolaja BA, Nikodinović-Runić J, Opsenica I. Synthesis and anti-Candida activity of novel benzothiepino[3,2-c]pyridine derivatives. in Chemical Biology and Drug Design. 2016;88(6):795-806. doi:10.1111/cbdd.12809 .
Božinović, Nina S., Šegan, Sandra B., Vojnović, Sandra, Pavić, Aleksandar, Šolaja, Bogdan A., Nikodinović-Runić, Jasmina, Opsenica, Igor, "Synthesis and anti-Candida activity of novel benzothiepino[3,2-c]pyridine derivatives" in Chemical Biology and Drug Design, 88, no. 6 (2016):795-806, https://doi.org/10.1111/cbdd.12809 . .