Computer‐aided drug design to explore cyclodextrin therapeutics and biomedical applications

Abstract

Cyclodextrin (CD) is a subset of the macrocyclic structural class, which is an important class of small organic agents that are useful functional excipients. They have wide range application possibilities in different fields of sciences such as material preparation, medicine, analytical chemistry, and separation processes. They are used widely in pharmaceutical formulations and drug delivery for increasing the water solubility of low soluble drugs and drug candidates. Due to the ring structure, they behave differently than smaller molecules and may be capable of hitting new classes of targets. A macrocyclic molecule presents varied functionality and stereochemical complexity in a pre-organized conformation of the ring structure. This can result in high selectivity and affinity for protein targets while conserving enough bioavailability to arrive at intracellular locations. Regardless of these valuable features, and the verified success of several marketed macrocycle drugs isolated from natural compounds, this class has been little explored in drug development. This study describes some of the key features of the CDs therapeutic discovery. Also, the application of computational chemistry approaches such as QSAR/QSPR, molecular docking, and molecular/quantum mechanics for modeling of CD-drug system is reviewed briefly. K E Y W O R D Sbioavailability, computational, cyclodextrin, drug design, drug discovery, macrocyclic, therapeutic

Application of Molecular Dynamics Simulations in the Analysis of Cyclodextrin Complexes

“…However, apart from MD, other techniques have been widely utilized in modeling CDs, i.e., molecular docking, quantitative structure-activity/property relationships (QSARs/QSPRs), Monte Carlo simulations, and machine learning methods. Those approaches have been briefly described in general reviews, focusing on application of molecular modeling methods in this field [15,16]. Therefore, they will not be discussed in this article.…”

Computational Methods for the Interaction between Cyclodextrins and Natural Compounds: Technology, Benefits, Limitations, and Trends

“…Tang et al 8 reviewed how to use MD simulations to study the binding kinetics of CDs and drug ligands. Recently, Abdolmaleki et al 9 summarized the application of QSAR, molecular docking, MD simulations, and quantum mechanics to study CD−drug inclusion complexes. The authors have outlined the applications of the above methods for studying CD−drug molecules.…”

Inhibition activity prediction for a dataset of candidates’ drug by combining fuzzy logic withMLR/ANN QSARmodels

“…The relations can be characterized as mathematical models, termed as structureactivity relationships (SARs) or quantitative structure-activity relationships (QSARs), collectively referred to as (Q)SARs. We have reviewed these concepts in details in other papers (Abdolmaleki & Ghasemi, 2017;Abdolmaleki, Ghasemi, & Ghasemi, 2017a;Abdolmaleki, Ghasemi, & Ghasemi, 2017b;Ahmadi, Khazaei, & Abdolmaleki, 2014). As a matter of fact, the reasoning based on the molecular structure has been the main engine for the great development of molecular sciences.…”