Discovery of Cinnamylidene Derivative of Rhodanine with High Anthelmintic Activity against Rhabditis sp.

Abstract

The treatment of parasitic infections requires the application of chemotherapy. In view of increasing resistance to currently in-use drugs, there is a constant need to search for new compounds with anthelmintic activity. A series of 16 cinnamylidene derivatives of rhodanine, including newly synthesized methoxy derivatives (1–11) and previously obtained chloro, nitro, and diethylamine derivatives (12–16), was investigated towards anthelmintic activity. Compounds (1–16) were evaluated against free-living nematodes of the genus Rhabditis sp. In the tested group of rhodanine derivatives, only compound 2 shows very high biological activity (LC50 = 0.93 µg/µL), which is higher than the reference drug albendazole (LC50 = 19.24 µg/µL). Crystal structures of two compounds, active 2 and inactive 4, were determined by the X-ray diffraction method to compare molecular geometry and search for differences responsible for observed biological activity/inactivity. Molecular modelling and selected physicochemical properties prediction were performed to assess the potential mechanism of action and applied in the search for an explanation as to why amongst all similar compounds only one is active. We can conclude that the tested compound 2 can be further investigated as a potential anthelmintic drug.

Evaluation of Anthelmintic and Anti-Inflammatory Activity of 1,2,4-Triazole Derivatives

“…Moreover, compound 14 , bearing 2-pyridyl and 4-methylphenyl substituents, was characterized by anthelmintic activity (LC 50 = 6.550 ± 0.866 µg/µL). Both compounds were more effective than albendazole (LC 50 = 19.24 µg/µL) [ 49 ]. Derivative 18 possessed significant anthelmintic activity only at a dose of 1.1 µg/µL ( Figure 7 ).…”

“…Rhabditis sp. nematodes were used, among others, to determine the anthelmintic activity of the new rhodanine derivatives of cinnamaldehyde [ 49 ], naphthalimide—conjugates of boron clusters [ 51 ]—and thiosemicarbazide derivatives [ 24 ].…”

“… Viability (%) of Rhabditis sp. nematodes after 24 h exposure to increasing concentrations of the compounds ( a ) 12, ( b ) 14, ( c ) 18 and ( d ) albendazole [ 38 , 49 ] ( p < 0.05 *, p < 0.01 **, p < 0.001 ***). …”

Architecture of the rings of 5-arylidenerhodanine derivatives versus P-gp inhibition

“…The family of rhodanine derivatives is of interest in medicinal chemistry because of their various biological actions, for example, antibacterial (Maddila et al, 2020;Tejchman et al, 2020;Z ˙esławska et al, 2022a), antifungal (Chauhan et al, 2012), antiparasitic (Tejchman et al, 2022), anticancer (Yin et al, 2022), antidiabetic (Andleeb et al, 2016) and antiviral (Lesyk, 2020). Recently, 5-arylidenerhodanine derivatives have been studied as potential modulators of the MDR efflux pump P-gp (Z ˙esławska et al, 2022b).…”

Synthesis, Crystal Structures, Lipophilic Properties and Antimicrobial Activity of 5-Pyridylmethylidene-3-rhodanine-carboxyalkyl Acids Derivatives

“…Compounds containing the 2-sulfanylidene-1,3-thiazolidin-4-one core (rhodanine), the synthesis of which was first carried out by Nencki almost 150 years ago [1], have interesting biological properties and therefore are still of interest to researchers in the field of medicinal chemistry [2][3][4]. Such derivatives reveal, inter alia, antibacterial [5,6], antifungal [7,8], antiviral [9,10], antitumor [11][12][13][14], anti-inflammatory [15] and anthelmintic [16] activities. Other, non-medical applications of rhodanine derivatives are also known.…”