Figueroa-Valverde LAURO, Diaz-Cedillo FRANCISCO, Rosas-Nexticapa MARCELA, Garcimarero-Espino E. ALEJANDRA, Mateu-Armand VIRGINA, Hernandez-Vazquez PATRICA, Benitez-Coeto LAURA, Hau-Heredia LENIN, Pool Gómez EDUARDO, Lopez-Ramos MARIA, Borges-Ballote YARİTZA

İki Azete Steroid Türevinin Basit Sentezi ve Aromataz Enzimi ile Etkileşiminin Teorik Olarak Değerlendirilmesi

Meme kanserinin tedavisi için birkaç aromataz inhibitörü kullanılmıştır; ancak, bu ilaçların bazıları endometrial kanser ve kemik kaybı gibi bazı yan etkiler yaratabilir. Bu çalışmanın amacı, bir yerleştirme modelinde kontroller olarak anastrozol ve exemestan kullanarak teorik etkileşimini bir aromataz enzimi (2wd3) ile teorik etkileşimini değerlendirmek için iki yeni azete-steroid türevini (bileşik 9 veya 10) sentezlemekti. 9 ve 10’un hazırlanması, aminasyon, eterleştirme, nitrasyon ve ekleme içeren bir dizi reaksiyon kullanılarak gerçekleştirildi. Bileşiklerin kimyasal yapısı element analizi ve NMR spektrumu kullanılarak doğrulandı. Sonuçlar, bileşikler 9 veya 10’un, anastrozol ve exemestan ile karşılaştırıldığında 2wd3 protein yüzeyinde yer alan farklı tipte bir amino asit tortusuna bağlanabileceğini gösterdi; bu fenomen, aromataz enziminin biyolojik aktivitesinde değişiklikler yapabilir. Tüm veriler, bileşik 9 veya 10’un, meme kanseri tedavisinde bir alternatif olabileceğini göstermektedir; bu nedenle ilaç endüstrisi için iyi bir aday olabilir.

Facile Synthesis of Two Azete-Steroid Derivatives and Theoretical Evaluation of Its Interaction with the Aromatase Enzyme

Several aromatase inhibitors have used for the treatment of breast cancer; however, some of these drugs may produce someside effects such as endometrial cancer and bone loss. The aim of this study was to synthesize two new azete-steroid derivatives (compounds 9 or 10) to evaluate its theoretical interaction with an aromatase enzyme (2wd3) using anastrozole andexemestane as controls in a docking model. The preparation of 9 and 10 was carried out using a series of reactions which involvesamination, etherification, nitration, and addition. Chemical structure of the compounds was confirmed using elemental analysisand NMR spectrum. The results showed that compounds 9 or 10 could bind to a different type of aminoacid residues involved inof 2wd3 protein surface compared anastrozole and exemestane; this phenomenon may exert changes in the biological activity ofaromatase enzyme. All data suggest that compounds 9 or 10 could be an alternative for the treatment of breast cancer; thereforeit could be a good candidate for the pharmaceutical industry.

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