Remapping the Chemical Space and the Pharmacological Space of Drugs: What Can We Expect from the Road Ahead?

This work examines the current landscape of drug discovery and development, with a particular focus on the chemical and pharmacological spaces. It emphasizes the importance of understanding these spaces to anticipate future trends in drug discovery. The use of cheminformatics and data analysis enabled in silico exploration of these spaces, allowing a perspective of drugs, approved drugs after 2020, and clinical candidates, which were extracted from the newly released ChEMBL34 (March 2024).

Molecular hybridization: a powerful tool for multitarget drug discovery.

Introduction: The current drug discovery paradigm of 'one drug, multiple targets' has gained attention from both the academic medicinal chemistry community and the pharmaceutical industry. This is in response to the urgent need for effective agents to treat multifactorial chronic diseases. The molecular hybridization strategy is a useful tool that has been widely explored, particularly in the last two decades, for the design of multi-target drugs.

Stereochemical insights into β-amino--acylhydrazones and their impact on DPP-4 inhibition.

Dipeptidyl peptidase IV (DPP-4) is a key enzyme that regulates several important biological processes and it is better known to be targeted by gliptins as a modern validated approach for the management of type 2 diabetes mellitus (T2DM). However, new generations of DPP-4 inhibitors capable of controlling inflammatory processes associated with chronic complications of T2DM are still needed. In this scenario, we report here the design by molecular modelling of new β-amino--acylhydrazones, their racemic synthesis, chiral resolution, determination of physicochemical properties and their DPP4 inhibitory potency.

The Magic Methyl and Its Tricks in Drug Discovery and Development.

One of the key scientific aspects of small-molecule drug discovery and development is the analysis of the relationship between its chemical structure and biological activity. Understanding the effects that lead to significant changes in biological activity is of paramount importance for the rational design and optimization of bioactive molecules. The "methylation effect", or the "magic methyl" effect, is a factor that stands out due to the number of examples that demonstrate profound changes in either pharmacodynamic or pharmacokinetic properties.

Discovery of Putative Dual Inhibitor of Tubulin and EGFR by Phenotypic Approach on LASSBio-1586 Homologs.

Combretastatin A-4 (CA-4, ) is an antimicrotubule agent used as a prototype for the design of several synthetic analogues with anti-tubulin activity, such as LASSBio-1586 (). A series of branched and unbranched homologs of the lead-compound and vinyl, ethinyl and benzyl analogues, were designed and synthesized. A comparison between the cytotoxic effect of these homologs and on different human tumor cell lines was performed from a cell viability study using MTT with 48 h and 72 h incubations.