Targeted synthesis of a trimethoxyphenyltetrahydropyrimidine analogue designed as a DNA intercalator: <i>in silico</i>, multi-spectroscopic, thermodynamic, and <i>in vitro</i> approaches.

ABSTRACT: Based on the rational design of DNA intercalators and Topo-II inhibitors and taking into consideration the main pharmacophoric features of doxorubicin (Dox) as a reference standard, we theoretically designed novel substituted tetrahydropyrimidine analogues (T_1-35). The designed analogues (T_1-35) were investigated for their inhibitory potential towards the hybrid DNA and Topo-II target receptor using molecular docking. Interestingly, the theoretically designed analogue T₃₀ with a 3,4,5-trimethoxy phenyl side chain was found to be the superior candidate, achieving a binding score of -7.06 kcal mol^-1, compared with two reference standards, doxorubicin (Dox) and a co-crystal ligand (EVP). Moreover, the docked candidates (T₃₀, Dox, and EVP)

SUBMITTER: Al-Karmalawy AA 

PROVIDER: S-EPMC12061050 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature