Huntington Hastalığının Tedavisi İçin Yeni Dihidrokromeno¬kromendiol Türevlerinin ADMET Özellikleri ve Geniş Spektrumlu Biyoaktivitesinin In Silico Değerlendirilmesi

Öz

Bu çalışmada, Huntington hastalığının (HD) tedavisinde potansiyel kullanım olasılığı belir-lenmiş bazı dihidrokromenokromeno-diol türevi bileşiklerin ADMET ve geniş spektrumlu biyoaktivite özellikleri incelenmiştir. Bu amaçla, öncelikle moleküllerin ADMET kapsamındaki fizikokimyasal özellikleri, lipofilisite, suda çözünürlük, absorpsiyon, dağılım, metabolizma ve atılım, toksisite, çevresel toksisite, Tox21 yolakları ve medikal kimya özel-likleri değerlendirilmiştir. Geniş spektrumlu biyoaktivite açısından ise sıçanlarda akut tok-sisite, ilaçların kardiyovasküler ve hepatobiliyer sistemler üzerindeki yan etkileri, antibak-teriyel aktivite, antifungal aktivite, anti-HIV aktivite, antiviral aktivite ve tümör ile tümör olmayan hücre hatlarıyla etkileşim değerleri hesaplanmıştır. Elde edilen tüm hesaplamalar sonucunda, 3 numaralı molekülün(2,7-dietil-3,8-dimetil-5,10-dihidrokromeno[5,4,3-cde]kromene-5,10-diol) ADMET ve geniş spektrumlu biyoaktivite açısından HD tedavisi için ideal bir aday molekül olabileceği sonucuna varılmıştır.

Anahtar Kelimeler

• Huntington hastalığı
• ADMET
• biyoaktivite
• dihidrokromenokromeno-diol türevleri
• yeni ilaç

In Silico Evaluation of ADMET and Broad-Spectrum Bioactivity of Some dihydrochromenochromene-diol Derivatives Novel Drug Candidates for Huntington’s Disease Treatment

Öz

In this study, we determined the ADMET and broad-spectrum bioactivity properties of some dihydrochromenochromene-diol derived compounds that have been identified as having po-tential for use in the treatment of Huntington's disease (HD). To this end, we first examined the physicochemical, lipophilicity, water solubility, absorption, distribution, metabolism and excretion, toxicity, environmental toxicity, Tox21 pathway, and medicinal chemistry proper-ties of the molecules considered within the scope of ADMET. In terms of broad spectrum bioactivity, acute toxicity in rats, side effects of drugs on the cardiovascular and hepatobili-ary systems, antibacterial activity, antifungal activity, anti-HIV activity, antiviral activity, and interaction with tumor and non-tumor cell lines values were calculated. Based on all the calculations obtained, it was concluded that molecule 3 (2,7-diethyl-3,8-dimethyl-5,10-dihydrochromeno[5,4,3-cde]chromene-5,10-diol) could be an ideal molecule for the treat-ment of HD in terms of ADMET and broad spectrum bioactivity.

Anahtar Kelimeler

• Huntington's disease
• ADMET
• bioactivity
• dihydrochromenochromene-diol derivatives
• nov-el drug

Kaynakça

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