Principles and Applications of Molecular Hybridization in Drug Design and Development

Review Article

Abstract

Molecular hybridization is a valuable technique in drug design and development, including both chemical and biological aspects of molecular interactions. The concept extends from the fundamental orbital theory explaining molecular geometry to advanced drug design approaches for creating multi-target therapeutic agents. At the atomic level, hybridization describes the mixing of atomic orbitals to form new hybrid orbitals that determine molecular structure and reactivity patterns. In drug development, molecular hybridization involves the strategic combination of distinct pharmacophores or bioactive molecules through covalent bonding, resulting in hybrid compounds with enhanced therapeutic profiles. The methodology has evolved significantly since its introduction by Nicki in 1886, leading to various classification systems based on linking patterns and interaction modes. Modern applications include the development of dual-acting agents, particularly relevant in addressing complex diseases like cancer and neurodegenerative disorders. The use of computational tools, including molecular docking and MM-GBSA analyses, has further refined the hybrid molecule design process. Additionally, molecular hybridization principles find extensive applications in biotechnology through techniques such as Northern blotting, Southern blotting, and in situ hybridization, enabling precise detection and analysis of nucleic acid sequences. The convergence of these various aspects of molecular hybridization has significantly contributed to advancing both basic research and therapeutic development