Synthesis and Antiparasitic Activity of New Conjugates—Organic Drugs Tethered to Trithiolato-Bridged Dinuclear Ruthenium(II)–Arene Complexes

Desiatkina, Oksana; Johns, Serena K.; Anghel, Nicoleta; Boubaker, Ghalia; Hemphill, Andrew; Furrer, Julien; Păunescu, Emilia (2021). Synthesis and Antiparasitic Activity of New Conjugates—Organic Drugs Tethered to Trithiolato-Bridged Dinuclear Ruthenium(II)–Arene Complexes. Inorganics, 9(8), p. 59. MDPI 10.3390/inorganics9080059

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Tethering known drugs to a metalorganic moiety is an efficient approach for modulating
the anticancer, antibacterial, and antiparasitic activity of organometallic complexes. This study focused
on the synthesis and evaluation of new dinuclear ruthenium(II)–arene compounds linked to
several antimicrobial compounds such as dapsone, sulfamethoxazole, sulfadiazine, sulfadoxine,
triclosan, metronidazole, ciprofloxacin, as well as menadione (a 1,4‐naphtoquinone derivative). In
a primary screen, 30 compounds (17 hybrid molecules, diruthenium intermediates, and antimicrobials)
were assessed for in vitro activity against transgenic T. gondii tachyzoites constitutively expressing
β‐galactosidase (T. gondii β‐gal) at 0.1 and 1 μM. In parallel, the cytotoxicity in noninfected
host cells (human foreskin fibroblasts, HFF) was determined by an alamarBlue assay. When assessed
at 1 μM, five compounds strongly impaired parasite proliferation by >90%, and HFF viability
was retained at 50% or more, and they were further subjected to T. gondii β‐gal dose‐response studies.
Two compounds, notably 11 and 13, amide and ester conjugates with sulfadoxine and metronidazole,
exhibited low IC50 (half‐maximal inhibitory concentration) values 0.063 and 0.152 μM, and
low or intermediate impairment of HFF viability at 2.5 μM (83 and 64%). The nature of the anchored
drug as well as that of the linking unit impacted the biological activity.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Parasitology
08 Faculty of Science > Department of Chemistry, Biochemistry and Pharmaceutical Sciences (DCBP)

UniBE Contributor:

Desiatkina, Oksana; Johns, Serena Kudzai; Anghel, Nicoleta; Boubaker, Ghalia; Hemphill, Andrew; Furrer, Julien and Paunescu, Emilia

Subjects:

500 Science > 570 Life sciences; biology
500 Science > 540 Chemistry
600 Technology > 630 Agriculture

ISSN:

2304-6740

Publisher:

MDPI

Language:

English

Submitter:

Julien Henri Lucien Furrer

Date Deposited:

02 Aug 2021 11:56

Last Modified:

02 Aug 2021 11:56

Publisher DOI:

10.3390/inorganics9080059

BORIS DOI:

10.48350/157703

URI:

https://boris.unibe.ch/id/eprint/157703

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