Activity Modeling of Some Potent Inhibitors Against Mycobacterium tuberculosis Using Genetic Function Approximation Approach

Yıl 2019, Cilt: 9 Sayı: 1, 77 - 98, 28.06.2019

Shola Elijah Adenıjı Sani Uba Adamu Uzaıru

Öz

Objectives: The research aimed
to develop a theoretical (QSAR) model for
predicting the activity of 1,2,4-Triazole derivatives as anti-tubercular
antagonist.

Methods: Genetic function approximation (GFA) was employed
on a dataset of 1,2,4-Triazole derivatives to investigate their activities behavior on mycobacterium tuberculosis. This  approach led
to selection of the optimum descriptors and to generate the correlation QSAR
model that relate their activities
values against mycobacterium
tuberculosis with the molecular structures of the inhibitors.

Results: The built
model was validated and was found to have squared correlation coefficient (R²)
of 0.9134,
adjusted squared correlation
coefficient (R_adj) of 0.8753 and Leave one out (LOO) cross validation
coefficient () value of 0.8231. The external validation set used for
confirming the predictive power of the model has R²pred of 0.7482.

Conclusion:
Reliability, stability and robustness of the model obtained by the validation
test indicate that the model can be used to design and synthesis other
1,2,4-Triazole derivatives with improved anti-tubercular  activities.

Anahtar Kelimeler

Applicability domain, Genetic function approximation, QSAR, Tuberculosis

Genetik Fonksiyon Tahmin Yaklaşımı Kullanılarak Mycobacterium tuberculosis’e Karşı Bazı Etkili İnhibitörlerin Aktivite Modellemelerinin Yapılması

Öz

Amaç: Araştırma, anti-tüberküler antagonisti olarak
1,2,4-Triazol türevlerinin aktivitesini tahmin etmeye yönelik teorik (QSAR) bir
model geliştirmeyi amaçlamıştır.

Yöntem: Genetik fonksiyon yaklaşımı (GFA),
1,2,4-Triazol türevlerinin Mycobacterium tuberculosis üzerine etki
tarzlarını araştırmak amacıyla kullanılmıştır. Bu yaklaşım, optimum
tanımlayıcıların seçimine ve Mycobacterium tuberculosis üzerine etki
değerlerini inhibitörlerin moleküler yapılarıyla ilişkilendiren korelasyon QSAR
modelinin oluşturulmasına imkân vermiştir.

Sonuç: Oluşturulan model doğrulanmış ve korelasyon
katsayısının karesi (R²) 0.9134, düzeltilmiş korelasyon katsayısının
karesi (R_adj) 0.8753 ve tek-çıkışlı (LOO) çapraz doğrulama katsayı () değeri 0.8231 olarak bulunmuştur.
Modelin öngörücü gücünü doğrulamak için kullanılan harici doğrulama seti,
0.7482  'ye sahiptir.

Tartışma: Doğrulama testi ile elde edilen modelin güvenilirliği, kararlılığı ve
sağlamlığı, modelin, gelişmiş anti-füberküler aktivitesine sahip diğer
1,2,4-Triazol türevlerini tasarlamak ve sentezlemek için kullanılabileceğini
göstermektedir.

Anahtar Kelimeler

Uygulanabilirlik etki alanı, Genetik fonksiyon yaklaşımı, QSAR, Tüberkülosis, Triazol

Kaynakça

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