A conceptual review of rhodanine: current applications of antiviral drugs, anticancer and antimicrobial activities

Figures & data

Figure 1. Chemical structure of Rhodanine monomer [167].

Figure 2. Chemical structures of rhodanine and its analogues [136].

Figure 3. Hepatitis C virus NS3 inhibitors [136].

Figure 4. Hepatitis C virus NS5B inhibitors [136].

Figure 5. (1) Addition of a reactive cysteine thiol group to the exocyclic double bond of 5 arylmethylidene rhodanines; (2) Crystal structure of a Rhodanine- based inhibitor (in grey sticks) covalently bound to the Cys366 side chain in the allosteric binding site of HCV RNA polymerase NS5B (in cyan, PDB entry: 2AWZ) [113,168].

Figure 6. Representative inhibitors of (1) HIV-1 integrase and (2) gp41 [136].

Figure 7. 2D structures of HIV-1 inhibitors previously published [166].

Figure 8. Synthesis of aldehyde 6 and derivatives 9a–f. Synthesis scheme of aldehyde 6: (i) Pd (PPh3)2Cl2, Na2CO3, DMF/EtOH, RT, 1h; (ii) 1N NaOH (aq), MeOH/THF, reflux 2h. Synthesis scheme of derivatives 9a–f: (iii) DME, Et3N, MW(300 W), 90ÊC, 10 min. (iv) aldehyde 6, MW(300 W), 1100C, 5 min [166].

Table 1. Results of in vitro ADME analysis for selected rhodanine derivatives [166].

Compound	In vitro ADME
	Water Solub. (μg/mL)	Papp (1·10-6cm/sec)	Metabolic Stability (%)	Kd HSA (μM)	Kd BSA (μM)
1	0.88 ± 0.10	1.28	>90%	0.63 ± 0.1	0.68 ± 0.1
2	0.52 ± 0.13	1.26	>90%	0.96 ± 0.1	0.63 ± 0.1
9a	0.54 ± 0.08	0.4	>90%	1.51 ± 0.2	1.08 ± 0.2
9b	0.10 ± 0.08	2.32	>90%	1.57 ± 0.2	1.55 ± 0.3
9c	0.30 ± 0.07	1.23	>90%	1.19 ± 0.1	1.05 ± 0.1
9d	0.25 ± 0.09	1.50	>90%	1.09 ± 0.9	0.99 ± 0.9
9e	0.72 ± 0.12	0.92	>90%	2.19 ± 1.0	1.07 ± 0.9
9f	0.73 ± 0.14	0.87	>90%	2.23 ± 1.2	1.09 ± 0.9

Figure 9. Rhodanines with potential anticancer activity [169].

Figure 10. Structure of some antimicrobial rhodanines [170].

Figure 11. General approaches to rhodanines synthesis and transformation [170].

Figure 12. Chemical structure of rhodanine and thiohydantoin derivatives reported previously [148].

Figure 13. (A) The addition of a nucleophilic sulfhydryl group to the exocyclic double bond of 5 benzylidenerhodanines, (B) Crystal structure of the rhodanine-based inhibitor covalently bound to Cys366 in the active site of HCV RNA polymerase NS5B (PDB code: 2AWZ) [136].

Figure 14. Different types of substituted thiazolidinones (X = O, S) [1].

Figure 15. Synthesis of thiazolidine-2,4-dione using thiourea and chloroacetic acid [1].

Figure 16. Formula of the compounds A₁–A₂₃ [163].

Figure 17. Schematic illustration of the synthesis of the silver nanoparticle-embedded polyrhodanine nanotubes [165].

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