Special Issue: Advances in the Synthesis of Biologically Important Intermediates/Drugs

Chemical synthesis is a cornerstone of the development of medicinal chemistry, forming the basis for discovering compounds with new physical and/or biological properties. It allows for the construction of novel molecules and drugs that are more efficient, selective, and with reduced side effects. Furthermore, the control of molecules via synthesis permits innovative investigation into biological systems. This Special Issue aimed to collect studies utilizing chemical synthesis from organic and inorganic chemistry that explored recent advances in method development on synthesizing biologically essential intermediates/drugs. A total of six papers (four research papers and two review papers) relevant to the theme have been presented in this Special Issue.

The review paper by Kudelko et al. [1] outlines the literature from 2009 to 2022 on arylation reactions synthesizing 2,5-diaryl-1,3,4-oxadiazole derivatives. The 1,3,4-oxadiazole moiety is unique due to its range of biological activities, such as antibacterial, antifungal, antitumor, and anti-inflammatory properties. These derivatives have also been applied to pharmacology and the agricultural sector. The second review, by Sinicropi et al. [2], highlights the importance of chirality for drug activity with some significative examples of chiral drugs currently used in therapy. They provide a comprehensive list of different classes of chiral drugs, namely: those acting on the cardiovascular system, beta-adrenergics, those acting on the central nervous system, local anesthetics, non-steroidal anti-inflammatory drugs, antimicrobials, proton pump inhibitors, anticancer drugs, anti-histamines, selective serotonin reuptake inhibitors, serine protease inhibitors, and repositioned chiral drugs, to illustrate how enantiomeric purity plays a vital role in terms of drug efficacy. Capozzi et al. [3] tested aminobenzylnaphthol-derived products from the Betti reaction as potential antiproliferative agents, particularly against human Caco-2 adenocarcinoma and SH-SY5Y neuroblastoma cells. Gianluigi Franci et al. [4] assessed the antibacterial activity of plant-derived compounds, such as 4,5′′-dihydroxy-anthraquinone-2-carboxylic acid (Rhein), against S. aureus bacterial strains. Their findings suggest that Rhein could be a promising therapeutic option for treating S. aureus infections. Using liquid chromatography mass-spectrometer analysis, Adeniyi et al. [5] identified 262 potential antileukemia candidates from three traditional herbal concoctions against FLAT3, BCL-2, and mutated BCL-2 G101V targets. The top four hit inhibitors were then narrowed down using molecular docking and consensus methods. Kadela-Tomanek et al. [6] reported new derivatives of 6,7-dichloro-5,8-quinolinediones to be suitable substrates for the DT-diaphorase enzyme (highly expressed in most human solid tumors). Their experimental and theoretical findings suggest that the type of substituent at the C2 position of the 5,8-quinolinedione scaffold affects the enzymatic conversion rates.

Although submissions for this Special Issue have been closed, a plethora of research continues to report the much-needed advances in the chemical synthesis of biologically important intermediates/drugs toward societal benefit.