Pharmacophore Modeling in Drug Discovery: Methodology and Current Status

Abstract

A pharmacophore describes the framework of molecular features that are vital for the biological activity of a compound. Pharmacophore models are built by using the structural information about the active ligands or targets. The pharmacophore models developed are used to identify novel compounds that satisfy the pharmacophore requirements and thus expected to be biologically active. Drug discovery process is a challenging task that requires the contribution of multidisciplinary approaches. Pharmacophore modeling has been used in various stages of the drug discovery process. The major application areas are virtual screening, docking, drug target fishing, ligand profiling, and ADMET prediction. There are several pharmacophore modeling programs in use. The user must select the right program for the right purpose carefully. There are new developments in pharmacophore modeling with the involvement of the other computational methods. It has been integrated with molecular dynamics simulations. The latest computational approaches like machine learning have also played an important role in the advances achieved. Moreover, with the rapid advance in computing capacity, data storage, software and algorithms, more advances are anticipated. Pharmacophore modeling has contributed to a faster, cheaper, and more effective drug discovery process. With the integration of pharmacophore modeling with the other computational methods and advances in the latest algorithms, programs that have better perfomance are emerging. Thus, improvements in the quality of the phamacophore models generated have been achieved with this new developments.

Design, synthesis andin vitroevaluation of the hybrids of oxindolylidene and imidazothiazolotriazine as efficient antiproliferative agents

“…The application of pharmacophore fragments is a promising approach in drug design that continues to be important for contemporary medicinal chemistry. 2 Oxindole is a critical pharmacophore in the structures of some antitumor agents approved for clinical application, such as tyrosine-kinase inhibitors sunitinib, nintedanib, semaxanib and orantinib (Fig. 1).…”

Pharmacophore study, molecular docking and molecular dynamic simulation of virgin coconut oil derivatives as anti-inflammatory agent against COX-2

“…The utilization of pharmacophore is to determine molecular similarity for alignment of ligand and protein structure and also to characterize the molecular frameworks that are essential for a specific biological property [ 30 ]. Pharmacophores are based on the chemical properties of functional groups which are definable as an aromatic (ARO), hydrogen donor (HD), hydrogen acceptor (HA), hydrophobic (HP), negative ion (NI), or positive ion (PI) via the pharmit server.…”

“…Conventional medicinal development procedures are time-consuming and expensive, leading to the development of cost-effective and quick computational techniques for the creation and screening of potent drugs for clinical use [ 30 ]. Drugs passing the green light may be repurposed as an alternate means of screening for the rapid detection of probable lead sources to an disorder [ 37 ].…”

A novel family of small molecule HIF-1 alpha stabilizers for the treatment of diabetic wounds; an integratedin silico,in vitro, andin vivostrategy

“…This approach quickly finds all candidate pharmacophores and reports the one with the highest score. 11 …”

“…This approach quickly nds all candidate pharmacophores and reports the one with the highest score. 11 2.2.1 Virtual screening. The obtained pharmacophore model was used as the 3D query for screening the ZINC purchasable database.…”