Identifying structural features related to the biological activity of a series of AT1 antagonists from fragment-based drug design.
Antagonists of AT1 receptor are interesting substances to develop drugs that can be used for the treatment of hypertension and other diseases that affect the cardiovascular system. This study investigates the main interactions between various AT1 antagonists and the biological target by applying fragment-based drug design (Hologram QSAR - HQSAR). The proposed HQSAR model yielded significant correlation coefficients (q(2) = 0.764 and r(2) = 0.914), indicating that the method is rigorous and reliable. All models were externally validated using a test set and the results showed good agreement between the experimental and predicted data (r(2) test = 0.740). Therefore, our model can positively contribute to understand the structural features involved in the main interactions between the AT1 antagonists and the residues of the binding site.
Danielle
D
da C Silva
Vinícius G
VG
Maltarollo
School of Arts, Sciences, and Humanities, University of Sao Paulo, Sao Paulo, Brazil. kmhonorio@usp.br.
Kathia M
KM
Honorio
D047228:Angiotensin II Type 1 Receptor Blockers / Q000737:chemistry* / Q000494:pharmacology*; D015195:Drug Design; D006801:Humans; D008958:Models, Molecular; D021281:Quantitative Structure-Activity Relationship; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*
D047228:Angiotensin II Type 1 Receptor Blockers; D044140:Receptor, Angiotensin, Type 1