What place does molecular topology have in today’s drug discovery?

ABSTRACT

Introduction

Most methods in molecular and drug design are currently based on physicochemical descriptors. However, molecular topology, which relies on topological descriptors, has also shown value for molecular design even if it does not take into account the physical or chemical properties of ligands and receptors, including the ligand-receptor interaction itself.

Areas covered

Herein, the authors provide new insights into the importance of molecular topology according to some of the latest discoveries in physics and chemistry. Furthermore, the authors report on the most significant achievements in drug design using molecular topology over the last 5 years and give their expert perspectives on the subject as a whole.

Expert opinion

Molecular topology is a new paradigm which is independent of physicochemical molecular descriptors. This fact explains the viability of both the discovery of new lead compounds with a minimum of information derived from mathematical-topological patterns and the interpretation results in structural and physicochemical terms.

KEYWORDS:

• Molecular topology
• QSAR
• drug design
• molecular design
• computer aided drug design

Article highlights

• Most methods in molecular and drug design are based on physicochemical (in the last analysis physical) descriptors.

• Molecular topology is a new paradigm which is independent of physicochemical molecular descriptors.

• Molecular Topology can be exploited in drug design and development for the identification of new hit and lead.

• Molecular Topology has led to the discovery of several, new active molecules in different pharmacological and biological areas.

• Molecular Topology allows the discovery of new lead compounds with a minimum of information derived from mathematical-topological patterns, as well as results interpretation in structural and physicochemical terms.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

Authors acknowledge support from the MINECO (Spanish Ministry of Economy, Industry,, and Competitivity) via Project: ‘Desarrollo de nuevas herramientas para el control de oidios’ (AGL2016-76216-C2-2-R). Maria Galvez-Llompart thanks the Generalitat Valenciana (GVA) for a postdoctoral contract APOSTD/2019/055.