From Medicinal Chemistry to Human Health: Current Approaches to Drug Discovery for Cancer and Neglected Tropical Diseases.

Leonardo G Ferreira,Glaucius Oliva,Adriano D Andricopulo

doi:10.1590/0001-3765201820170505

Leonardo G Ferreira, Glaucius Oliva + Show 1 more

Open Access

https://doi.org/10.1590/0001-3765201820170505

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Abstract

Scientific and technological breakthroughs have compelled the current players in drug discovery to increasingly incorporate knowledge-based approaches. This evolving paradigm, which has its roots attached to the recent advances in medicinal chemistry, molecular and structural biology, has unprecedentedly demanded the development of up-to-date computational approaches, such as bio- and chemo-informatics. These tools have been pivotal to catalyzing the ever-increasing amount of data generated by the molecular sciences, and to converting the data into insightful guidelines for use in the research pipeline. As a result, ligand- and structure-based drug design have emerged as key pathways to address the pharmaceutical industry's striking demands for innovation. These approaches depend on a keen integration of experimental and molecular modeling methods to surmount the main challenges faced by drug candidates - in vivo efficacy, pharmacodynamics, metabolism, pharmacokinetics and safety. To that end, the Laboratório de Química Medicinal e Computacional (LQMC) of the Universidade de São Paulo has developed forefront research on highly prevalent and life-threatening neglected tropical diseases and cancer. By taking part in global initiatives for pharmaceutical innovation, the laboratory has contributed to the advance of these critical therapeutic areas through the use of cutting-edge strategies in medicinal chemistry.

Highlights

Modern drug research and development (R&D) has experienced remarkable changes as technological and scientific developments in the past years have dramatically changed the pharmaceutical innovation process
In line with our ongoing efforts focused on the establishment of integrated computational and experimental platforms to investigate drug ADME, we have developed the Database for Pharmacokinetic Properties (PK/DB), which is a tool for pharmacokinetics prediction based on highly predictive quantitative structure-property relationships (QSPR) models (Moda et al 2008)
More efficient organic synthesis methods, chemical biology approaches and bio- and chemoinformatics strategies have dramatically changed the process by which an initial hit is converted into a marketable drug

Summary

Introduction

Modern drug research and development (R&D) has experienced remarkable changes as technological and scientific developments in the past years have dramatically changed the pharmaceutical innovation process. The incorporation of molecular and computational strategies to drug development along with organic synthesis approaches has led to a sharp increase in the availability of biological, structural and chemical data. These modern R&D strategies usually combine structure- and ligand-based drug design methods (SBDD and LBDD, respectively) and many different computational and experimental techniques.

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