o:2739 Discovery of new chemotypes of dual 5-HT2A/D2 receptor antagonists with a strategy of drug design methodologies en Aim: Through the application of structure- and ligand-based methods, the authors aimed to create an integrative approach to developing a computational protocol for the rational drug design of potent dual 5-HT2A/D2 receptor antagonists without off-target activities on H1 receptors. Materials & methods: Molecular dynamics and virtual docking methods were used to identify key interactions of the structurally diverse antagonists in the binding sites of the studied targets, and to generate their bioactive conformations for further 3D-quantitative structure–activity relationship modeling. Results & conclusion: Toward the goal of finding multi-potent drugs with a more effective and safer profile, the obtained results led to the design of a new set of dual antagonists and opened a new perspective on the therapy for complex brain diseases. 3D-QSAR • 5-HT2A • D2 • fragment-based drug design • H1 • molecular docking • molecular dynamics simulations 1552099 10.4155/fmc-2021-0340 1552101 1756-8919 2023-09-01T13:11:44.343Z 44 no 46 Milica Radan Institut za proučavanje lekovitog bilja "Dr Josif Pančić" 0000-0002-6727-7624 46 Teodora Đikić Univerzitet u Beogradu, Farmaceutski fakultet 46 Katarina Nikolić Univerzitet u Beogradu, Farmaceutski fakultet application/pdf 9864729 https://unilib.phaidrabg.rs/o:2739 no yes 1 70 92000001 71A10 1 Future Medicinal Chemistry 14 13 963 989 2022