Application of Quantitative Structure-Activity Relationships in the Prediction of New Compounds with Anti-Leukemic Activity

Author(s)

Sandoval, Cristian ; Torrens, Francisco ; Godoy, Karina ; Reyes, Camila ; Farias, Jorge

• Document type: Journal article
• Source: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 24, n. 15, p. 12-pg., 2023-08-01.

Abstract

Leukemia invades the bone marrow progressively and, through unknown mechanisms, outcompetes healthy hematopoiesis. Protein arginine methyltransferases 1 (PRMT1) are found in prokaryotes and eukaryotes cells. They are necessary for a number of biological processes and have been linked to several human diseases, including cancer. Small compounds that target PRMT1 have a significant impact on both functional research and clinical disease treatment. In fact, numerous PRMT1 inhibitors targeting the S-adenosyl-L-methionine binding region have been studied. Through topographical descriptors, quantitative structure-activity relationships (QSAR) were developed in order to identify the most effective PRMT1 inhibitors among 17 compounds. The model built using linear discriminant analysis allows us to accurately classify over 90% of the investigated active substances. Antileukemic activity is predicted using a multilinear regression analysis, and it can account for more than 56% of the variation. Both analyses are validated using an internal "leave some out" test. The developed model could be utilized in future preclinical experiments with novel drugs. (AU)

• FAPESP's process: 20/06982-3 - Chimeric and pegylated L-asparaginase: study of the conditions of expression, production and purification of an innovative anti-leukemic biopharmaceutical with low immunogenic potential
• Grantee: Adalberto Pessoa Junior
• Support Opportunities: Regular Research Grants