Novel N3 substituted derivatives of 4-iminothiazolidine-2-one were synthesised under the reactions of [2+3]cyclocondensation, thionation and aminolysis. The functionalisation of 3-phenyl-4-imino-thiazolydine-2-one was carried out in its C5 position under condensation Knoevenagel and nitrosation reactions. The antioxidant activity of the synthesised compounds was evaluated in vitro by the method of their scavenging effect on 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals. When compared with existing antioxidants, some of our compounds were found to be more potent.
The data on the pharmacology of 4‐thiazolidinones showed that 5‐ene‐2‐(imino)amino‐4‐thiazolidinones are likely to comprise one of the most promising groups of compounds possessing anticancer properties. A series of 5‐arylidene‐2‐(4‐hydroxyphenyl)aminothiazol‐4(5H)‐ones was designed, synthesized, and studied against 10 leukemia cell lines, including the HL‐60, Jurkat, K‐562, Dami, KBM‐7, and some Ba/F3 cell lines. The structure–activity relationship analysis shows that almost all tested 5‐arylidene‐2‐(4‐hydroxyphenyl)aminothiazol‐4(5H)‐ones were characterized by ІС50 values lower or comparable to that of the control drug chlorambucil. Among the tested compounds, (5Z)‐5‐(2‐methoxybenzylidene)‐ (12), (5Z)‐(2‐ethoxybenzylidene)‐ (21), (5Z)‐5‐(2‐benzyloxybenzylidene)‐ (25), and (5Z)‐5‐(2‐allyloxybenzylidene)‐2‐(4‐hydroxyphenylamino)thiazol‐4(5H)‐ones (28) possessed the highest antileukemic activity at submicromolar concentrations (ІС50 = 0.10–0.95 µM).
Abstract.Following the N-alkylation reaction of starting 2-chloro-N-(5-aryl-1,3,4-oxadiazol-2-yl)-acetamides 1a-c with 2,4-thiazolidinedione or 5-sudstituted isatins the corresponding non-condensed oxadiazole derivatives with thiazolidine 2a-c or isatin 4a-h fragments were synthesized. The obtained compounds have been used in Knoevenagel condensation with 5R-isatin (for 2a-c) or 4-thiazolidinone derivatives (for 4a-h) for synthesis of the appropriate 5-ylidenederivatives 3a-g, 5a-k and 6a-d. Anticancer activity of eight synthesized compounds was evaluated toward 60 human tumor cell lines panel in National Cancer Institute.
1,3,4-Oxadiazole scaffold is one of the most important heterocyclic fragments, which is considered as a perspective building block for drug discovery. Substituted 1,3,4-oxadiazoles had been reported to display a diverse range of pharmacological activities including anticancer, anti-inflammatory, antitubercular, antibacterial, antiviral, antifungal, insecticidal, antioxidant, and analgesic activities. Moreover, the 1,3,4-oxadiazole core is a structural component of approved antiretroviral (Raltegravir), anticancer (Zibotentan), and antihypertensive (Tiodazosin and Nesapidil) drugs. In the present review, we summarized the literature data about the main approaches for obtaining possible directions of structural modification and pharmacological activity of noncondensed heterocyclic systems based on the 1,3,4-oxadiazole ring as promising objects for modern bioorganic and medicinal chemistry.
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