Evaluation of the antiparasitic activities of imidazol‐2‐ylidene–gold(I) complexes

• Published in: Archiv der Pharmazie (Weinheim) Vol. 353; no. 5; pp. e1900363 - n/a
• Main Authors: Koko, Waleed S., Jentzsch, Jana, Kalie, Hussein, Schobert, Rainer, Ersfeld, Klaus, Al Nasr, Ibrahim S., Khan, Tariq A., Biersack, Bernhard
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 01.05.2020; Wiley Subscription Services, Inc
• Subjects: antiparasitic drugs; Antiprotozoal Agents - chemical synthesis; Antiprotozoal Agents - chemistry; Antiprotozoal Agents - pharmacology; Chemistry; Chemistry, Medicinal; Chemistry, Multidisciplinary; Dose-Response Relationship, Drug; gold; Gold - chemistry; Gold - pharmacology; Imidazoles - chemistry; Imidazoles - pharmacology; Leishmania major - drug effects; Life Sciences & Biomedicine; metal‐based drugs; Molecular Structure; neglected tropical diseases; N‐heterocyclic carbene; Organogold Compounds - chemical synthesis; Organogold Compounds - chemistry; Organogold Compounds - pharmacology; Parasitic Sensitivity Tests; Pharmacology & Pharmacy; Physical Sciences; Protozoa; Science & Technology; Structure-Activity Relationship; Toxoplasma - drug effects; Trypanosoma brucei brucei - drug effects; gold; N-heterocyclic carbene; neglected tropical diseases; ASSAY; antiparasitic drugs; TOXOPLASMA-GONDII; PROLIFERATION; FERROCENYL; metal-based drugs; CARBENE COMPLEXES; GOLD(I)
• ISSN: 0365-6233; 1521-4184
• DOI: 10.1002/ardp.201900363

A series of cationic gold(I)–carbene complexes with various 4,5‐diarylimidazolylidene ligands were either newly prepared or repurposed for testing against protozoal Leishmania major, Toxoplasma gondii, and Trypanosoma brucei parasites. The syntheses of the new complexes 1b and 1c were described. Ferrocene compound 1a showed the highest activities against L. major amastigotes and T. gondii and distinct selectivity for T. gondii cells when compared with the activity against nonmalignant Vero cells. The ferrocene derivatives 1a–c are generally more active against the L. major amastigotes and the T. gondii tachyzoites than the other tested anisyl gold complexes and the approved drugs atovaquone and amphotericin B. Compounds 1a and 1e showed the highest selectivities for L. major amastigotes. Compounds 1d and 1f showed the highest selectivities for L. major promastigotes; 1f was the most active compound against L. major promastigotes of this series of compounds. The 3,4,5‐trimethoxyphenyl analog 1b also exhibited a much greater selectivity for T. b. brucei cells when compared with its activity against human HeLa cells. A series of newly synthesized or repurposed gold(I)–carbene complexes showed high activities against Toxoplasma gondii, Trypanosoma brucei, and Leishmania major protozoal parasites, with reasonable selectivities. They are promising drug candidates for the treatment of infections by these parasites