N 3 (194) 2025. P. 92–97

SEARCH FOR COMPOUNDS WITH ANTITUMOUR ACTIVITY AMONG 5-ISATINYLIDENE-SUBSTITUTED RHODANINE DERIVATIVES WITH BENZOTHIAZOLE MOIETY IN THE MOLECULES

L. M. Mosula, Yu. V. Olishchuk

Ivan Horbachevsky Ternopil National Medical University of the Ministry of Health of Ukraine, Ternopil, Ukraine

DOI 10.32782/2226-2008-2025-3-15

Introduction. The rhodanine scaffold is a well-known privileged heterocycle in Drug Development. Its derivatives have shown a broad spectrum of biological activity, including anticancer properties.

The aim of the work is assessment of the antitumour potential of 5-isatinylidene derivatives of N-(4-oxo-2-thioxothiazolidin-3-yl)-2-(2-oxobenzo[d]thiazol-3(2H)-yl)acetamide according to the prediction criteria via the online service.

Materials and methods. The series of compounds contains 17 derivatives. In silico predictions of the affinity of molecules to the biotargets and determination of their structural similarity to known drugs with establishment of the ATC code was performed using web tool SuperPred 3.0.

Results and discussion. The potential biological activity of derivatives 4–17 was compared with the in vitro efficacy of the core heterocycle, previously synthesized compounds 1–3 and the known effect of the drug Sutent (Pfizer Inc., USA). We determined the important role of 5-isatinylidene moiety on the increase of the probable antitumour activity in comparison to the unsubstituted core heterocycle. We established the group structural similarity to antitumour agents. The commonly predicted targets are Cathepsin D, Nuclear factor NF-kappa-B p105 subunit і Cyclin-dependent kinase 5/CDK5 activator 1 with binding probabilities in the range of 85.32–99.76% (Model accuracy ˃90%). Conclusions. The highest probability of structural similarity to antineoplastic drugs is predicted for the compound 4 (33.43%), and compound 5 is considered a potential multi-hitter. The most prospective for Drug Development are compounds 4, 6, 11 with potential activity 97.04%, 97.87% and 99.76%, respectively to targets CDK5, NF-kB1 p105, Cath-D (Model accuracy 93.0–98.95%). For hit compounds affinity for common targets is predicted to be higher than for previously studied compounds and Sutent. The prediction results confirmed the viability of further research. The obtained information could be of benefit to the design of new, effective small molecules with anticancer potential.

Keywords: rhodanine, benzothiazole, isatin, Drug Development, relationship ‘chemical structure – biological activity’.

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