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.

A series of Schiff base ligands obtained by the condensation of trans-cyclohexane-1,2-diamine and fluorinated benzaldehydes were prepared, followed by their reduction with NaBH₄. The reduced ligands were employed in the synthesis of zinc complexes of the general formula [ZnCl₂(L)]. The structures of both the original and the reduced Schiff bases, as well as of the zinc complexes, were characterized by single-crystal X-ray analysis, along with NMR and IR spectroscopy. The antimicrobial activities of the reduced Schiff bases and their zinc complexes were evaluated in vitro against E. coli, S. aureus, and C. albicans. The compounds containing the 4-(trifluoromethylphenyl) moiety showed marked antibacterial activity. Interestingly, the antimicrobial effect of the zinc complex with this moiety was significantly higher than that of the corresponding free reduced ligand, comparable with ciprofloxacin used as standard. Thus, a synergic effect upon the complexation with zinc can be inferred.

Several novel copper (II) complexes of reduced Schiff bases containing fluoride substituents were prepared and structurally characterized by single-crystal X-ray diffraction. The complexes exhibited diverse structures, with the central atom in distorted tetrahedral geometry. The biological effects of the products were evaluated, specifically their cytotoxicity, antimicrobial, and antiurease activities, as well as affinity for albumin (BSA) and DNA (ct-DNA). The complexes showed marked cytotoxic activities in the HepG2 hepatocellular carcinoma cell line, considerably higher than the standard cisplatin. The cytotoxicity depended significantly on the substitution pattern. The best activity was observed in the complex with a trifluoromethyl group in position 4 of the benzene ring—the dichloro[(±)-trans-N,N′-bis-(4-trifluoromethylbenzyl)-cyclohexane-1,2-diamine]copper (II) complex, whose activity (IC₅₀ 28.7 μM) was higher than that of the free ligand and markedly better than the activity of the standard cisplatin (IC₅₀ 336.8 μM). The same complex also showed the highest antimicrobial effect in vitro. The affinity of the complexes towards bovine serum albumin (BSA) and calf thymus DNA (ct-DNA) was established as well, indicating only marginal differences between the complexes. In addition, all complexes were shown to be excellent inhibitors of the enzyme urease, with the IC₅₀ values in the lower micromolar region.