Investigation on Quantitative Structure-Activity Relationships of 1,3,4-Oxadiazole Derivatives as Potential Telomerase Inhibitors

Abstract

A series of 1,3,4-oxadiazole derivatives with significant broad-spectrum anticancer activity against different cell lines, and demonstrated telomerase inhibition, was subjected to Quantitative Structure-Activity Relationships (QSAR) analysis. Validated models with high correlation coefficients were developed. The Multiple Linear Regression (MLR) models, by Ordinary Least Squares (OLS), showed good robustness and predictive capability, according to the Multi-Criteria Decision Making (MCDM = 0.8352), a technique that simultaneously enhances the performances of a certain number of criteria. The descriptors selected for the models, such as electrotopological state (E-state) descriptors, and extended topochemical atom (ETA) descriptors, showed the relevant chemical information contributing to the activity of these compounds. The results obtained in this study make sure about the identification of potential hits as prospective telomerase inhibitors.

Telomere dysfunction in some pediatric congenital and growth-related diseases

“…Telomere overexpression is common in most patients with pediatric cancers; hence, inhibiting telomerase activity may be a potential therapeutic target. The 1,3,4-Oxadiazole scaffold is a five-member heterocyclic ring, which can be used as a telomerase inhibitor in tumor therapy ( 111 , 112 ). As a telomerase inhibitor, imetelstat also plays a significant role in the treatment of adult AML ( 113 ).…”

Predicting Skin Permeability by Means of Computational Approaches: Reliability and Caveats in Pharmaceutical Studies

“…permeability coefficient) through a mathematical equation. QSPRs have traditionally been generated for molecules associated with a measurable property [51][52][53] , in this case mainly the Log K p . But more generically, even binary or categorical responses (e.g.…”

“…QSPRs have traditionally been generated for molecules associated with a measurable property, − in this case mainly the Log K p . But more generically, even binary or categorical responses (e.g., not-permeable or permeable) have been used, applying discriminant analysis, logistic regression, and classification methods such as random forest (RF), support vector machine (SVM), and bayesian classifiers. − …”

In Silico Design, Synthesis, and Biological Evaluation of Anticancer Arylsulfonamide Endowed with Anti-Telomerase Activity

“…Several other compounds designed using in silico approaches have been tested as potential inhibitors of the catalytic subunit of telomerase such as benzylidene-hydrazone analogs [22], dihydropyrazole [23][24][25][26][27][28][29], dibenzopyrroles [30], flavone pyridines [31], 1,3,4-oxadiazole derivatives [32][33][34][35][36], pyrazole-5-carboxamides and pyrazole-pyrimidines [37], spiroketals [37], celastrol derivatives [38], myricetin derivatives [39], indolyl-2'-deoxynucleotide analogs [40], flavonoid derivatives [41], and chrolactomycin derivatives [42]. Other classes of compounds developed as telomerase inhibitors are reported in two recent reviews [43,44].…”