Academic Journal
Προβολή σε EDS

Synthesis, Characterization, and In Vitro and In Silico Studies of New Triazole Derivatives as Aromatase Inhibitors.

Λεπτομέρειες βιβλιογραφικής εγγραφής
Τίτλος: Synthesis, Characterization, and In Vitro and In Silico Studies of New Triazole Derivatives as Aromatase Inhibitors.
Συγγραφείς: Uzmez ZL; Faculty of Pharmacy, Anadolu University, Eskişehir 26470, Turkey., Osmaniye D; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, Turkey.; Central Analysis Laboratory, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, Turkey., Ozkay Y; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, Turkey.; Central Analysis Laboratory, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, Turkey., Kaplancıklı ZA; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, Turkey.
Πηγή: Medicinal chemistry (Shariqah (United Arab Emirates)) [Med Chem] 2025; Vol. 21 (4), pp. 309-318.
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Bentham Science Publishers Country of Publication: Netherlands NLM ID: 101240303 Publication Model: Print Cited Medium: Internet ISSN: 1875-6638 (Electronic) Linking ISSN: 15734064 NLM ISO Abbreviation: Med Chem Subsets: MEDLINE
Imprint Name(s): Publication: Amsterdam : Bentham Science Publishers
Original Publication: Sharjah, U.A.E.; San Francisco, CA : Bentham Science Publishers
Ιατρικοί όροι (MeSH): Aromatase Inhibitors*/pharmacology , Aromatase Inhibitors*/chemical synthesis , Aromatase Inhibitors*/chemistry , Triazoles*/pharmacology , Triazoles*/chemical synthesis , Triazoles*/chemistry , Antineoplastic Agents*/chemical synthesis , Antineoplastic Agents*/pharmacology , Antineoplastic Agents*/chemistry, Aromatase/metabolism ; Cell Proliferation/drug effects ; Humans ; Structure-Activity Relationship ; Molecular Docking Simulation ; Drug Screening Assays, Antitumor ; MCF-7 Cells ; Molecular Structure ; A549 Cells ; Dose-Response Relationship, Drug
Περίληψη: Introduction: Breast cancer is the most common type of cancer among women. Steroidal or non-steroidal aromatase inhibitors (NSAIs) are used clinically, and in most cancer diseases, resistance is the most important problem.
Methods: The nitrogenous heterocyclic ring is noteworthy in the structure of non-steroidal aromatase inhibitors. This is the pharmacophore structure for aromatase inhibition. Because the enzyme interacts with the Fe2+ cation of the HEM structure in its active site, the most used agents in the clinic, such as anastrozole and letrozole, contain triazoles in their structures. Within the scope of this study, hybrid compounds containing both imidazole and triazole were synthesized.
Results: The synthesis was carried out by a 4-step reaction. The anticancer effects of the compounds were evaluated by MTT assay performed on A549 and MCF-7 cancer cells. Compound 4d showed anticancer activity against the MCF-7 cell line with IC50=6.7342 uM value. This compound exhibited anticancer activity against the A549 cell line with an IC50 = 17.1761 μM. In the MTT test performed on a healthy cell line to determine the cytotoxic effects of the compounds, the compound showed activity with a value of 4d IC50=13.2088 uM. This indicates that the compound is not cytotoxic. Additionally, BrdU analysis was performed to evaluate whether the compound inhibits DNA synthesis. These selective effects of the compounds on breast cancer strengthened their aromatase enzyme inhibitor potential. For this reason, experiments conducted with both in vitro and in silico methods revealed a compound with high aromatase inhibitor potential.
Conclusion: The interactions observed as a result of molecular docking and dynamics studies are in harmony with activity studies. In particular, interactions with HEM600 demonstrate the activity potential of the compound.
(Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
References: Bioorg Chem. 2019 Dec;93:103327. (PMID: 31614285)
Eur J Med Chem. 2011 Sep;46(9):4010-24. (PMID: 21703734)
Molecules. 2021 Jul 02;26(13):. (PMID: 34279404)
Eur J Med Chem. 2022 Oct 5;240:114569. (PMID: 35834906)
Eur J Med Chem. 2021 Jan 15;210:112979. (PMID: 33183865)
Eur J Med Chem. 2022 Dec 15;244:114802. (PMID: 36240547)
Eur J Med Chem. 2021 Dec 15;226:113837. (PMID: 34530384)
Biotechnol Annu Rev. 2005;11:127-52. (PMID: 16216776)
Nature. 2009 Jan 8;457(7226):219-23. (PMID: 19129847)
Bioorg Med Chem. 2015 Jul 1;23(13):3472-80. (PMID: 25934226)
J Biomol Struct Dyn. 2022 Oct;40(17):7991-8003. (PMID: 33970806)
Eur J Med Chem. 2020 Jan 1;185:111815. (PMID: 31732252)
CA Cancer J Clin. 2014 Jan-Feb;64(1):9-29. (PMID: 24399786)
ChemMedChem. 2008 Nov;3(11):1708-30. (PMID: 18816537)
ChemMedChem. 2013 May;8(5):779-99. (PMID: 23495205)
Eur J Med Chem. 2021 Nov 15;224:113733. (PMID: 34364162)
Bioorg Chem. 2022 May;122:105709. (PMID: 35255344)
Bioorg Med Chem. 2016 Oct 1;24(19):4723-4730. (PMID: 27567077)
Int J Mol Sci. 2021 Oct 02;22(19):. (PMID: 34639036)
J Chem Theory Comput. 2017 Apr 11;13(4):1518-1524. (PMID: 28267328)
Eur J Med Chem. 2021 Feb 5;211:113115. (PMID: 33360796)
Eur J Med Chem. 2013 Nov;69:99-114. (PMID: 24012714)
Eur J Med Chem. 2021 Nov 15;224:113737. (PMID: 34365129)
Spectrochim Acta A Mol Biomol Spectrosc. 2022 Nov 5;280:121530. (PMID: 35752037)
Grant Information: 1919B012201803 Research Fund of Tubitak 2209-A project
Contributed Indexing: Keywords: Breast cancer; aromatase inhibitor; estrogen.; molecular docking; molecular dynamics; triazole
Substance Nomenclature: 0 (Aromatase Inhibitors)
0 (Triazoles)
0 (Antineoplastic Agents)
EC 1.14.14.1 (Aromatase)
Entry Date(s): Date Created: 20250512 Date Completed: 20250512 Latest Revision: 20251114
Update Code: 20260130
PubMed Central ID: PMC12606616
DOI: 10.2174/0115734064316112240722092935
PMID: 40351069
Βάση Δεδομένων: MEDLINE
FullText Text:
  Availability: 0
Header DbId: cmedm
DbLabel: MEDLINE
An: 40351069
AccessLevel: 3
PubType: Academic Journal
PubTypeId: academicJournal
PreciseRelevancyScore: 0
IllustrationInfo
Items – Name: Title
  Label: Title
  Group: Ti
  Data: Synthesis, Characterization, and In Vitro and In Silico Studies of New Triazole Derivatives as Aromatase Inhibitors.
– Name: Author
  Label: Authors
  Group: Au
  Data: <searchLink fieldCode="AU" term="%22Uzmez+ZL%22">Uzmez ZL</searchLink>; Faculty of Pharmacy, Anadolu University, Eskişehir 26470, Turkey.<br /><searchLink fieldCode="AU" term="%22Osmaniye+D%22">Osmaniye D</searchLink>; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, Turkey.; Central Analysis Laboratory, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, Turkey.<br /><searchLink fieldCode="AU" term="%22Ozkay+Y%22">Ozkay Y</searchLink>; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, Turkey.; Central Analysis Laboratory, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, Turkey.<br /><searchLink fieldCode="AU" term="%22Kaplancıklı+ZA%22">Kaplancıklı ZA</searchLink>; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, Turkey.
– Name: TitleSource
  Label: Source
  Group: Src
  Data: <searchLink fieldCode="JN" term="%22101240303%22">Medicinal chemistry (Shariqah (United Arab Emirates))</searchLink> [Med Chem] 2025; Vol. 21 (4), pp. 309-318.
– Name: TypePub
  Label: Publication Type
  Group: TypPub
  Data: Journal Article
– Name: Language
  Label: Language
  Group: Lang
  Data: English
– Name: TitleSource
  Label: Journal Info
  Group: Src
  Data: <i>Publisher: </i><searchLink fieldCode="PB" term="%22Bentham+Science+Publishers%22">Bentham Science Publishers </searchLink><i>Country of Publication: </i>Netherlands <i>NLM ID: </i>101240303 <i>Publication Model: </i>Print <i>Cited Medium: </i>Internet <i>ISSN: </i>1875-6638 (Electronic) <i>Linking ISSN: </i><searchLink fieldCode="IS" term="%2215734064%22">15734064 </searchLink><i>NLM ISO Abbreviation: </i>Med Chem <i>Subsets: </i>MEDLINE
– Name: PublisherInfo
  Label: Imprint Name(s)
  Group: PubInfo
  Data: <i>Publication</i>: Amsterdam : Bentham Science Publishers<br /><i>Original Publication</i>: Sharjah, U.A.E.; San Francisco, CA : Bentham Science Publishers
– Name: SubjectMESH
  Label: MeSH Terms
  Group: Su
  Data: <searchLink fieldCode="MM" term="%22Aromatase+Inhibitors%22">Aromatase Inhibitors*</searchLink>/<searchLink fieldCode="MM" term="%22Aromatase+Inhibitors+pharmacology%22">pharmacology</searchLink> <br /><searchLink fieldCode="MM" term="%22Aromatase+Inhibitors%22">Aromatase Inhibitors*</searchLink>/<searchLink fieldCode="MM" term="%22Aromatase+Inhibitors+chemical+synthesis%22">chemical synthesis</searchLink> <br /><searchLink fieldCode="MM" term="%22Aromatase+Inhibitors%22">Aromatase Inhibitors*</searchLink>/<searchLink fieldCode="MM" term="%22Aromatase+Inhibitors+chemistry%22">chemistry</searchLink> <br /><searchLink fieldCode="MM" term="%22Triazoles%22">Triazoles*</searchLink>/<searchLink fieldCode="MM" term="%22Triazoles+pharmacology%22">pharmacology</searchLink> <br /><searchLink fieldCode="MM" term="%22Triazoles%22">Triazoles*</searchLink>/<searchLink fieldCode="MM" term="%22Triazoles+chemical+synthesis%22">chemical synthesis</searchLink> <br /><searchLink fieldCode="MM" term="%22Triazoles%22">Triazoles*</searchLink>/<searchLink fieldCode="MM" term="%22Triazoles+chemistry%22">chemistry</searchLink> <br /><searchLink fieldCode="MM" term="%22Antineoplastic+Agents%22">Antineoplastic Agents*</searchLink>/<searchLink fieldCode="MM" term="%22Antineoplastic+Agents+chemical+synthesis%22">chemical synthesis</searchLink> <br /><searchLink fieldCode="MM" term="%22Antineoplastic+Agents%22">Antineoplastic Agents*</searchLink>/<searchLink fieldCode="MM" term="%22Antineoplastic+Agents+pharmacology%22">pharmacology</searchLink> <br /><searchLink fieldCode="MM" term="%22Antineoplastic+Agents%22">Antineoplastic Agents*</searchLink>/<searchLink fieldCode="MM" term="%22Antineoplastic+Agents+chemistry%22">chemistry</searchLink><br /><searchLink fieldCode="MH" term="%22Aromatase%22">Aromatase</searchLink>/<searchLink fieldCode="MH" term="%22Aromatase+metabolism%22">metabolism</searchLink> ; <searchLink fieldCode="MH" term="%22Cell+Proliferation%22">Cell Proliferation</searchLink>/<searchLink fieldCode="MH" term="%22Cell+Proliferation+drug+effects%22">drug effects</searchLink> ; <searchLink fieldCode="MH" term="%22Humans%22">Humans</searchLink> ; <searchLink fieldCode="MH" term="%22Structure-Activity+Relationship%22">Structure-Activity Relationship</searchLink> ; <searchLink fieldCode="MH" term="%22Molecular+Docking+Simulation%22">Molecular Docking Simulation</searchLink> ; <searchLink fieldCode="MH" term="%22Drug+Screening+Assays%2C+Antitumor%22">Drug Screening Assays, Antitumor</searchLink> ; <searchLink fieldCode="MH" term="%22MCF-7+Cells%22">MCF-7 Cells</searchLink> ; <searchLink fieldCode="MH" term="%22Molecular+Structure%22">Molecular Structure</searchLink> ; <searchLink fieldCode="MH" term="%22A549+Cells%22">A549 Cells</searchLink> ; <searchLink fieldCode="MH" term="%22Dose-Response+Relationship%2C+Drug%22">Dose-Response Relationship, Drug</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Introduction: Breast cancer is the most common type of cancer among women. Steroidal or non-steroidal aromatase inhibitors (NSAIs) are used clinically, and in most cancer diseases, resistance is the most important problem.<br />Methods: The nitrogenous heterocyclic ring is noteworthy in the structure of non-steroidal aromatase inhibitors. This is the pharmacophore structure for aromatase inhibition. Because the enzyme interacts with the Fe<superscript>2+</superscript> cation of the HEM structure in its active site, the most used agents in the clinic, such as anastrozole and letrozole, contain triazoles in their structures. Within the scope of this study, hybrid compounds containing both imidazole and triazole were synthesized.<br />Results: The synthesis was carried out by a 4-step reaction. The anticancer effects of the compounds were evaluated by MTT assay performed on A549 and MCF-7 cancer cells. Compound 4d showed anticancer activity against the MCF-7 cell line with IC<subscript>50</subscript>=6.7342 uM value. This compound exhibited anticancer activity against the A549 cell line with an IC<subscript>50</subscript> = 17.1761 μM. In the MTT test performed on a healthy cell line to determine the cytotoxic effects of the compounds, the compound showed activity with a value of 4d IC<subscript>50</subscript>=13.2088 uM. This indicates that the compound is not cytotoxic. Additionally, BrdU analysis was performed to evaluate whether the compound inhibits DNA synthesis. These selective effects of the compounds on breast cancer strengthened their aromatase enzyme inhibitor potential. For this reason, experiments conducted with both in vitro and in silico methods revealed a compound with high aromatase inhibitor potential.<br />Conclusion: The interactions observed as a result of molecular docking and dynamics studies are in harmony with activity studies. In particular, interactions with HEM600 demonstrate the activity potential of the compound.<br /> (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
– Name: Ref
  Label: References
  Group: RefInfo
  Data: Bioorg Chem. 2019 Dec;93:103327. (PMID: <searchLink fieldCode="PM" term="%2231614285%22">31614285)</searchLink><br />Eur J Med Chem. 2011 Sep;46(9):4010-24. (PMID: <searchLink fieldCode="PM" term="%2221703734%22">21703734)</searchLink><br />Molecules. 2021 Jul 02;26(13):. (PMID: <searchLink fieldCode="PM" term="%2234279404%22">34279404)</searchLink><br />Eur J Med Chem. 2022 Oct 5;240:114569. (PMID: <searchLink fieldCode="PM" term="%2235834906%22">35834906)</searchLink><br />Eur J Med Chem. 2021 Jan 15;210:112979. (PMID: <searchLink fieldCode="PM" term="%2233183865%22">33183865)</searchLink><br />Eur J Med Chem. 2022 Dec 15;244:114802. (PMID: <searchLink fieldCode="PM" term="%2236240547%22">36240547)</searchLink><br />Eur J Med Chem. 2021 Dec 15;226:113837. (PMID: <searchLink fieldCode="PM" term="%2234530384%22">34530384)</searchLink><br />Biotechnol Annu Rev. 2005;11:127-52. (PMID: <searchLink fieldCode="PM" term="%2216216776%22">16216776)</searchLink><br />Nature. 2009 Jan 8;457(7226):219-23. (PMID: <searchLink fieldCode="PM" term="%2219129847%22">19129847)</searchLink><br />Bioorg Med Chem. 2015 Jul 1;23(13):3472-80. (PMID: <searchLink fieldCode="PM" term="%2225934226%22">25934226)</searchLink><br />J Biomol Struct Dyn. 2022 Oct;40(17):7991-8003. (PMID: <searchLink fieldCode="PM" term="%2233970806%22">33970806)</searchLink><br />Eur J Med Chem. 2020 Jan 1;185:111815. (PMID: <searchLink fieldCode="PM" term="%2231732252%22">31732252)</searchLink><br />CA Cancer J Clin. 2014 Jan-Feb;64(1):9-29. (PMID: <searchLink fieldCode="PM" term="%2224399786%22">24399786)</searchLink><br />ChemMedChem. 2008 Nov;3(11):1708-30. (PMID: <searchLink fieldCode="PM" term="%2218816537%22">18816537)</searchLink><br />ChemMedChem. 2013 May;8(5):779-99. (PMID: <searchLink fieldCode="PM" term="%2223495205%22">23495205)</searchLink><br />Eur J Med Chem. 2021 Nov 15;224:113733. (PMID: <searchLink fieldCode="PM" term="%2234364162%22">34364162)</searchLink><br />Bioorg Chem. 2022 May;122:105709. (PMID: <searchLink fieldCode="PM" term="%2235255344%22">35255344)</searchLink><br />Bioorg Med Chem. 2016 Oct 1;24(19):4723-4730. (PMID: <searchLink fieldCode="PM" term="%2227567077%22">27567077)</searchLink><br />Int J Mol Sci. 2021 Oct 02;22(19):. (PMID: <searchLink fieldCode="PM" term="%2234639036%22">34639036)</searchLink><br />J Chem Theory Comput. 2017 Apr 11;13(4):1518-1524. (PMID: <searchLink fieldCode="PM" term="%2228267328%22">28267328)</searchLink><br />Eur J Med Chem. 2021 Feb 5;211:113115. (PMID: <searchLink fieldCode="PM" term="%2233360796%22">33360796)</searchLink><br />Eur J Med Chem. 2013 Nov;69:99-114. (PMID: <searchLink fieldCode="PM" term="%2224012714%22">24012714)</searchLink><br />Eur J Med Chem. 2021 Nov 15;224:113737. (PMID: <searchLink fieldCode="PM" term="%2234365129%22">34365129)</searchLink><br />Spectrochim Acta A Mol Biomol Spectrosc. 2022 Nov 5;280:121530. (PMID: <searchLink fieldCode="PM" term="%2235752037%22">35752037)</searchLink>
– Name: GrantInfo
  Label: Grant Information
  Group: Grant
  Data: 1919B012201803 Research Fund of Tubitak 2209-A project
– Name: SubjectMinor
  Label: Contributed Indexing
  Group:
  Data: <i>Keywords: </i>Breast cancer; aromatase inhibitor; estrogen.; molecular docking; molecular dynamics; triazole
– Name: NumberCAS
  Label: Substance Nomenclature
  Group: ID
  Data: 0 (Aromatase Inhibitors)<br />0 (Triazoles)<br />0 (Antineoplastic Agents)<br />EC 1.14.14.1 (Aromatase)
– Name: DateEntry
  Label: Entry Date(s)
  Group: Date
  Data: <i>Date Created: </i>20250512 <i>Date Completed: </i>20250512 <i>Latest Revision: </i>20251114
– Name: DateUpdate
  Label: Update Code
  Group: Date
  Data: 20260130
– Name: PubmedCentralID
  Label: PubMed Central ID
  Group: ID
  Data: PMC12606616
– Name: DOI
  Label: DOI
  Group: ID
  Data: 10.2174/0115734064316112240722092935
– Name: AN
  Label: PMID
  Group: ID
  Data: 40351069
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=cmedm&AN=40351069
RecordInfo BibRecord:
  BibEntity:
    Identifiers:
      – Type: doi
        Value: 10.2174/0115734064316112240722092935
    Languages:
      – Code: eng
        Text: English
    PhysicalDescription:
      Pagination:
        StartPage: 309
    Subjects:
      – SubjectFull: Aromatase metabolism
        Type: general
      – SubjectFull: Cell Proliferation drug effects
        Type: general
      – SubjectFull: Humans
        Type: general
      – SubjectFull: Structure-Activity Relationship
        Type: general
      – SubjectFull: Molecular Docking Simulation
        Type: general
      – SubjectFull: Drug Screening Assays, Antitumor
        Type: general
      – SubjectFull: MCF-7 Cells
        Type: general
      – SubjectFull: Molecular Structure
        Type: general
      – SubjectFull: A549 Cells
        Type: general
      – SubjectFull: Dose-Response Relationship, Drug
        Type: general
      – SubjectFull: Aromatase Inhibitors pharmacology
        Type: general
      – SubjectFull: Aromatase Inhibitors chemical synthesis
        Type: general
      – SubjectFull: Aromatase Inhibitors chemistry
        Type: general
      – SubjectFull: Triazoles pharmacology
        Type: general
      – SubjectFull: Triazoles chemical synthesis
        Type: general
      – SubjectFull: Triazoles chemistry
        Type: general
      – SubjectFull: Antineoplastic Agents chemical synthesis
        Type: general
      – SubjectFull: Antineoplastic Agents pharmacology
        Type: general
      – SubjectFull: Antineoplastic Agents chemistry
        Type: general
    Titles:
      – TitleFull: Synthesis, Characterization, and In Vitro and In Silico Studies of New Triazole Derivatives as Aromatase Inhibitors.
        Type: main
  BibRelationships:
    HasContributorRelationships:
      – PersonEntity:
          Name:
            NameFull: Uzmez ZL
      – PersonEntity:
          Name:
            NameFull: Osmaniye D
      – PersonEntity:
          Name:
            NameFull: Ozkay Y
      – PersonEntity:
          Name:
            NameFull: Kaplancıklı ZA
    IsPartOfRelationships:
      – BibEntity:
          Dates:
            – D: 01
              M: 01
              Text: 2025
              Type: published
              Y: 2025
          Identifiers:
            – Type: issn-electronic
              Value: 1875-6638
          Numbering:
            – Type: volume
              Value: 21
            – Type: issue
              Value: 4
          Titles:
            – TitleFull: Medicinal chemistry (Shariqah (United Arab Emirates))
              Type: main
ResultId 1