From Psychoactivity to Antimicrobial Agents: Multifaceted Applications of Synthetic Cathinones and Catha edulis Extracts

Abstract

The emergence of new psychoactive substances (NPS) in the global drug market since the 2000s has posed major challenges for regulators and law enforcement agencies. Among these, synthetic cathinones have gained prominence due to their stimulant effects on the central nervous system, leading to widespread recreational use. These compounds, often marketed as alternatives to illicit stimulants such as amphetamines and cocaine, have been linked to numerous cases of intoxication, addiction and death. The structural diversity and enantiomeric forms of synthetic cathinones further complicate their detection and regulation and pose challenges to forensic toxicology. In addition to their psychoactive and toxicological effects, new research suggests that cathinones may have antimicrobial properties. Compounds derived from Catha edulis (khat), including cathinone, have shown antimicrobial activity against multidrug-resistant bacteria such as Staphylococcus aureus and Escherichia coli, highlighting their potential role in the fight against antibiotic resistance. This article provides an overview of the chemistry, pharmacokinetics, pharmacodynamics, toxicological effects and potential antimicrobial applications of synthetic cathinones. The potential therapeutic use of cathinone-derived compounds to combat antimicrobial resistance represents an exciting new frontier in drug development, although further research is needed to balance these benefits with the psychoactive risks.

Keywords: chirality enantioselectivity; drug design; enantioseparation; poisoning; synthetic cathinones.

Figure 1

Plant of khat and chemical structures of cathinone and cathine.

Figure 2

Formation of 3,6-dimethyl-2,5-diphenylpyrazine.

Figure 3

Chemical structure of cathinone, methamphetamine and methylenedioxymethamphetamine and the stereoisomers.

Figure 4

General structure of synthetic cathinones.

Figure 5

Chemical structure of synthetic N-alkylated cathinones.

Figure 6

Chemical structure of NEC, NEB, NEPD, NEH and NEHP.

Figure 7

Chemical structures of N-pyrrolidine cathinone derivatives. α-PPP (α-pyrrolidinopropiophenone).

Figure 8

Structural formulae of α-PVT and naphyrone.

Figure 9

Chemical structure of 3,4-methylenedioxy-N-pyrrolidine derivatives.

Figure 10

Chemical structure of 3,4-methylenedioxy-N-alkyl derivatives.

Figure 11

Tautomerism of synthetic cathinones.

Figure 12

General method of synthesis of synthetic cathinones from aryl ketones.

Figure 13

Generalized steps for the Neber rearrangement.

Figure 14

Possible mechanisms of formation of 2H-azirines by Neber rearrangement.

Figure 15

Synthesis of enantiomerically pure (S)-cathinone starting from (S)-alanine.

Figure 16

Synthesis of enantiomers of 4-methylcathinone, 4-methoxycathinone, 4-methylthiocathinone and 4-ethylthiocathinone (as hydrochloride salts).

Figure 17

Synthesis of (S) and (R)-methcathinone through oxidation of ephedrines and pseudoephedrines.

Figure 18

Synthesis of (S)-(−)-cathinone by resolution of norephedrine.

Figure 19

Analytical techniques for the separation of SC enantiomers.

Figure 20

Cyclodextrins used in capillary electrophoresis for the separation of synthetic cathinones.

Figure 21

Chiral derivation of synthetic cathinones from primary or secondary amines by L-TPC and (S)-MTPA chloride.

Figure 22

(A) Crown ether phase, (3,3′-diphenyl-1,1′-bonapthyl)-20-crown-6 and reaction with n –octyltriethoxysilane and (B) possible mode of chiral recognition of cathinones.

Figure 23

Chemical structures of polysaccharide-based chiral selectors.

Figure 24

Three types of ion exchange CSPs for chiral separation.

Figure 25

Classification of synthetic cathinones by pharmacological action.

Figure 26

Proposed metabolic pathways for mephedrone metabolism in humans (showing Phase I in black and Phase II in red).

Figure 27

Metabolites identified in the literature for methylone using cell cultures and animal models.

Figure 28

Chemical structures of MDPV metabolites observed in cell cultures and animal studies (highlighting the most abundant metabolites in blue).

Figure 29

Meso-aryl BODIPYs and Hydrazone-BODIPY Probes for Cathinone Detection.

Figure 30

Major clinical manifestations related to synthetic cathinone intoxication.