Analogues of Anticancer Natural Products: Chiral Aspects

Abstract

Life is chiral, as its constituents consist, to a large degree, of optically active molecules, be they macromolecules (proteins, nucleic acids) or small biomolecules. Hence, these molecules interact disparately with different enantiomers of chiral compounds, creating a preference for a particular enantiomer. This chiral discrimination is of special importance in medicinal chemistry, since many pharmacologically active compounds are used as racemates—equimolar mixtures of two enantiomers. Each of these enantiomers may express different behaviour in terms of pharmacodynamics, pharmacokinetics, and toxicity. The application of only one enantiomer may improve the bioactivity of a drug, as well as reduce the incidence and intensity of adverse effects. This is of special significance regarding the structure of natural products since the great majority of these compounds contain one or several chiral centres. In the present survey, we discuss the impact of chirality on anticancer chemotherapy and highlight the recent developments in this area. Particular attention has been given to synthetic derivatives of drugs of natural origin, as naturally occurring compounds constitute a major pool of new pharmacological leads. Studies have been selected which report the differential activity of the enantiomers or the activities of a single enantiomer and the racemate.

Determination of the Absolute Configuration of Secondary Alcohols in a Compound Mixture via the Application of Competing Enantioselective Acylation Coupled with LC/MS Analysis

“…Similarly, drugs or ligands designed to interact with exact biological receptors must have the correct stereochemistry to exert their intended effects. Different stereoisomers of a natural product exhibit distinct biological activities, pharmacological properties, and even varying degrees of toxicity [ 6 , 7 , 8 , 9 , 10 , 11 , 12 ]. Even subtle differences in stereochemistry can have profound effects on a compound’s biological activity.…”

“…The study of stereochemistry in natural products involves the analysis of chiral centers, stereoisomerism, and geometric isomerism. Understanding the stereochemistry of natural products is essential for medicinal chemists, pharmacologists, and researchers involved in drug discovery, providing insights into the design and optimization of bioactive compounds for therapeutic purposes [ 6 , 7 , 8 , 9 , 10 , 11 , 12 ].…”

Evaluation of Antitumor Activity of Xanthones Conjugated with Amino Acids

“…In fact, recent advances in this field allowed for the identification of several compounds with different pharmacologic activities, including anticancer. A xanthone scaffold is also a heterocyclic structure and has attracted attention in recent anticancer research [8]. Nature is the main source of chiral bioactive compounds, which can be used as therapeutic agents, such as xanthone derivatives.…”

“…Nature is the main source of chiral bioactive compounds, which can be used as therapeutic agents, such as xanthone derivatives. Many naturally occurring xanthones, isolated from plants and marine sources, are chiral and exhibit interesting biological activities [8][9][10][11]. Nevertheless, one of the main biological activities reported within this class of compounds is their antitumor activity [12][13][14].…”

Myrsinane-Type Diterpenes: A Comprehensive Review on Structural Diversity, Chemistry and Biological Activities

“…Natural products (NPs) have been crucial in drug discovery and development, with more than half of the current clinically used drugs based on natural compound pharmacophore [ 1 ]. In fact, over the last four decades, nearly two-thirds of medications containing novel chemical entities have come from NPs or chemically created analogues of NPs [ 2 ], highlighting their role in the treatment of cancer and infective diseases but also cardiovascular diseases and even diabetes and multiple sclerosis [ 3 ].…”