Novel Tricyclo[4.2.1]Nonane and Bicyclo[2.2.1]Heptane Derivatives: Synthesis, in Vitro Biological Activities and in Silico Studies

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dc.authoridCeylan, Mustafa/0000-0002-9184-4385
dc.contributor.authorSarikaya, Meryem Kececi
dc.contributor.authorYaglioglu, Ayse Sahin
dc.contributor.authorCeylan, Mustafa
dc.contributor.authorYirtici, Uemit
dc.date.accessioned2025-01-21T16:42:57Z
dc.date.available2025-01-21T16:42:57Z
dc.date.issued2024
dc.departmentKırıkkale Üniversitesi
dc.description.abstractThe target benzothiazole derivatives (8a-g) were synthesized starting from norbornene. The addition of dichloroketene to norbornene followed by the reduction of chlorine atoms were synthesized tricyclo[4.2.1.02,5]non-7-en-3-one (4). The condensation of benzaldehyde derivatives with compound 4 were obtained chalcone analogs (6a-g). Finally, benzothiazole derivatives (8a-g) were obtained by the reaction of the chalcone analogs with 2-aminobenzothiol in an acidic medium. The antiproliferative activities of compounds 6a-g and 8a-g were determined against C6 (rat brain tumor) and HeLa (human cervical carcinoma) cell lines using a BrdU cell proliferation ELISA assay with 5-fluorouracil (5-FU) as a standard. In both series, when compared with 5-FU (IC50=3.8 mu M for C6 and 16.33 mu M for HeLa), the most active compounds against C6 cells were 6a and 8g with IC50 values of 14.13 mu M and 29.99 mu M, respectively. With this, 6a, 6e, 6f, and 8b were the most active compounds against HeLa cells with IC50 values of 0.8, 1.21, 19.33 and 18.13 mu M, respectively. Additionally, the SwissADME online web tool was used to predict the physicochemical and ADME properties of the tested compounds. The results showed that all compounds possess promising predicted physiochemical and pharmacokinetic properties and comply with Lipinski's rule of 5, indicating that they are predicted to be orally bioavailable that they possess a predicted bioavailability score of 0.55. Furthermore, in the SwissADME Boiled-Egg chart, all compounds showed high predicted GIT absorption, while compounds 6a-g showed blood-brain barrier (BBB) permeation, and compounds 8a-g did not. Moreover, none of the compounds was (P-gp) substrates. This study investigated the potential interactions between the antiapoptotic proteins Bcl-2, Bcl-xl, Bcl-w, Brag-1, Bfl-1, and Mcl-1 and compounds 6a, 8b, and 8g through molecular docking studies. The findings suggest that these compounds may effectively inhibit antiapoptotic proteins, as evidenced by significant hydrogen bonds and hydrophobic interactions, particularly with Bcl-xl.
dc.description.sponsorshipDepartment of Chemistry at Gaziosmanpasa University; TUBITAK (Scientific and Technological Council of Turkey) [111T111]
dc.description.sponsorshipThe authors are indebted to the Department of Chemistry at Gaziosmanpasa University and the TUBITAK (Scientific and Technological Council of Turkey) (Project No. 111T111) for their support.
dc.identifier.doi10.1002/cbdv.202401980
dc.identifier.issn1612-1872
dc.identifier.issn1612-1880
dc.identifier.pmid39400495
dc.identifier.scopus2-s2.0-85209099750
dc.identifier.scopusqualityQ3
dc.identifier.urihttps://doi.org/10.1002/cbdv.202401980
dc.identifier.urihttps://hdl.handle.net/20.500.12587/25174
dc.identifier.wosWOS:001356818800001
dc.identifier.wosqualityN/A
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherWiley-V C H Verlag Gmbh
dc.relation.ispartofChemistry & Biodiversity
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.snmzKA_20241229
dc.subject2-alkylsubstitedbenzo[d]thiazoles; Antiproliferative activity; HeLa; C6; ADME prediction; in silico
dc.titleNovel Tricyclo[4.2.1]Nonane and Bicyclo[2.2.1]Heptane Derivatives: Synthesis, in Vitro Biological Activities and in Silico Studies
dc.typeArticle

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