An integrated approach towards the development of novel antifungal agents containing thiadiazole: synthesis and a combined similarity search, homology modelling, molecular dynamics and molecular docking study

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dc.authoridTAHTACI, HAKAN/0000-0002-1557-6315
dc.authoridEce, Abdulilah/0000-0002-3087-5145
dc.authoridCinaroglu, Suleyman Selim/0000-0001-7120-3540
dc.contributor.authorEr, Mustafa
dc.contributor.authorAbounakhla, Abdulati Miftah
dc.contributor.authorTahtaci, Hakan
dc.contributor.authorBawah, Ali Hasin
dc.contributor.authorCinaroglu, Suleyman Selim
dc.contributor.authorOnaran, Abdurrahman
dc.contributor.authorEce, Abdulilah
dc.date.accessioned2024-09-29T16:05:11Z
dc.date.available2024-09-29T16:05:11Z
dc.date.issued2018
dc.departmentKarabük Üniversitesien_US
dc.description.abstractBackgroundThis study aims to synthesise and characterise novel compounds containing 2-amino-1,3,4-thiadiazole and their acyl derivatives and to investigate antifungal activities. Similarity search, molecular dynamics and molecular docking were also studied to find out a potential target and enlighten the inhibition mechanism.ResultsAs a first step, 2-amino-1,3,4-thiadiazole derivatives (compounds 3 and 4) were synthesised with high yields (81 and 84%). The target compounds (6a-n and 7a-n) were then synthesised with moderate to high yields (56-87%) by reacting 3 and 4 with various acyl chloride derivatives (5a-n). The synthesized compounds were characterized using the IR, H-1-NMR, C-13-NMR, Mass, X-ray (compound 7n) and elemental analysis techniques. Later, the in vitro antifungal activities of the synthesised compounds were determined. The inhibition zones exhibited by the compounds against the tested fungi, their minimum fungicidal activities, minimum inhibitory concentration and the lethal dose values (LD50) were determined. The compounds exhibited moderate to high levels of activity against all tested pathogens. Finally, in silico modelling was used to enlighten inhibition mechanism using ligand and structure-based methods. As an initial step, similarity search was carried out and the resulting proteins that belong to Homo sapiens were used as reference in sequence similarity search to find the corresponding amino acid sequences in target organisms. Homology modelling was used to construct the protein structure. The stabilised protein structure obtained from molecular dynamics simulation was used in molecular docking.ConclusionThe overall results presented here might be a good starting point for the identification of novel and more active compounds as antifungal agents.en_US
dc.description.sponsorshipKarabuk University [KBU-BAP-17-YL-265]en_US
dc.description.sponsorshipThe financial support under the contract (KBU-BAP-17-YL-265) from the Karabuk University is gratefully acknowledged.en_US
dc.identifier.doi10.1186/s13065-018-0485-3
dc.identifier.issn1752-153X
dc.identifier.pmid30470928en_US
dc.identifier.scopus2-s2.0-85057089262en_US
dc.identifier.scopusqualityN/Aen_US
dc.identifier.urihttps://doi.org/10.1186/s13065-018-0485-3
dc.identifier.urihttps://hdl.handle.net/20.500.14619/6542
dc.identifier.volume12en_US
dc.identifier.wosWOS:000451019100001en_US
dc.identifier.wosqualityQ3en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherSpringeropenen_US
dc.relation.ispartofChemistry Central Journalen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subject2-Amino-1,3,4-thiadiazoleen_US
dc.subjectAcylationen_US
dc.subjectAntifungalen_US
dc.subjectHomology modellingen_US
dc.subjectMolecular dynamicsen_US
dc.subjectMolecular dockingen_US
dc.titleAn integrated approach towards the development of novel antifungal agents containing thiadiazole: synthesis and a combined similarity search, homology modelling, molecular dynamics and molecular docking studyen_US
dc.typeArticleen_US

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