DNA Cleavage Properties, Antimicrobial and Cytotoxic Activity and 4D-QSAR Analysis of Some Pyrazole Derivatives

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dc.authoridKOPRU, Semiha/0000-0002-2269-6980
dc.authoridSABANCI, NAZMIYE/0000-0002-0733-1692
dc.contributor.authorKopru, Semiha
dc.contributor.authorKup, Fatma Ozturk
dc.contributor.authorSabanci, Nazmiye
dc.contributor.authorCadir, Mehmet
dc.contributor.authorBulut, Duygu Cemre
dc.contributor.authorDuman, Fatih
dc.contributor.authorIlhan, Ilhan Ozer
dc.date.accessioned2024-12-24T19:30:36Z
dc.date.available2024-12-24T19:30:36Z
dc.date.issued2019
dc.departmentSiirt Üniversitesi
dc.description.abstractBackground: An extensive study of 19 pyrazole derivatives were carried out based on the evaluation of DNA cleavage properties, antimicrobial and cytotoxic activities and 4D-QSAR analysis including pharmacophore modelling and bioactivity prediction by the Electron Conformational-Genetic Algorithm (EC-GA) method. Methods: The pyrazole derivatives were tested for their antimicrobial activity against certain human pathogenic organisms using the agar diffusion procedure. Binding of compounds with DNA was studied by gel electrophoresis using plasmid pBR322 DNA. The compounds were investigated for their properties as cytotoxic agents by brine shrimp lethality bioassay. To identify the pharmacophoric elements and find out the most important molecular properties which govern cytotoxic activity, multiple conformations of the compounds were used. Results: The urea derivatives of pyrazole had higher antibacterial activities against Gram-negative bacteria than against Gram-positive bacteria. Many of the compounds were found to cleave plasmid pBR322 DNA from the supercoiled form to the nicked circular. The cytotoxicity values of the compounds ranged from 13.87 to 84.1 mu g/mL. The generated QSAR model was evaluated through the use of the Leave-One-Out Cross Validation (LOO-CV) method. A statistically significant and considerably predictive QSAR model was obtained with 4- descriptors resulting in R2 training = 0.8223, R2 test = 0.9346, q2=0.6201, q2 ext1 0.8672, q2 ext2= 0.8662 and q2 ext3=0.9511. Discussion: The generated model demonstrates that geometrical parameters are more correlated with cytotoxic activity. The resulting EC-GA model would provide benefits to design novel bioactive pyrazole derivatives which are more potent and have less side effects. Conclusion: It is believed that the generated QSAR model gives insight into developing new more potent pyrazole derivative drugs.
dc.description.sponsorshipScientific Research Projects Chairmanship (BAP) of Erciyes University [FBY-10-3329, FOA-2014-5365]
dc.description.sponsorshipThis work was supported by the Scientific Research Projects Chairmanship (BAP) of Erciyes University (Project Number: FBY-10-3329, Project Number: FOA-2014-5365).
dc.identifier.doi10.2174/1570180815666180926104319
dc.identifier.endpage918
dc.identifier.issn1570-1808
dc.identifier.issn1875-628X
dc.identifier.issue8
dc.identifier.scopus2-s2.0-85073672407
dc.identifier.scopusqualityQ3
dc.identifier.startpage904
dc.identifier.urihttps://doi.org/10.2174/1570180815666180926104319
dc.identifier.urihttps://hdl.handle.net/20.500.12604/7606
dc.identifier.volume16
dc.identifier.wosWOS:000480359800008
dc.identifier.wosqualityQ4
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.language.isoen
dc.publisherBentham Science Publ Ltd
dc.relation.ispartofLetters in Drug Design & Discovery
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.snmzKA_20241222
dc.subjectDNA cleavage
dc.subjectantimicrobial activity
dc.subjectcytotoxic activity
dc.subjectEC-GA method
dc.subject4D-QSAR
dc.subjectpyrazole
dc.titleDNA Cleavage Properties, Antimicrobial and Cytotoxic Activity and 4D-QSAR Analysis of Some Pyrazole Derivatives
dc.typeArticle

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