Abstract
Following of the chemical diversity of 4-thiazolidinones the in-house library of new heterocycles have been designed and synthesized (more 7000 compounds). Anticancer, antitrypanosomal, antituberculosis and antiviral activity screening led to SAR database formation; lead-compounds identification; design of focused sub-libraries; formation and validation of hypotheses for structure optimization: i) complications of C5 fragment and/or functionalization of N3 position; ii) creation of the hybrid molecules; iii) fixation of 5-ene-4-thiazolidinones in fused heterocycles via annulation (thiopyrano[2,3-d]thiazoles were found as a cyclic isosteric mimetics of 5-ene-4-thiazolidinones); iv) the leukemia panel was detected to be the most sensitive among all cancer cell lines. Following the in silico and pharmacological data for the investigation of molecular mechanism of anticancer effect the argument in favor of the apoptotic related and mild prooxidant actions for active compounds have been found.
Highlights
The in-house library of heterocycles has been an object for the study of anticancer activity within the NCI, NIH protocol [9,10,11]
Based on the obtained results, it was hypothesised that the heterocycles containing a “thiazolidinone matrix” have specific anti-leukaemia activity
It is of note that the significant values of the correlation coefficients of thiazolidinone derivatives from different sub-libraries to the S-trityl-L-cysteine, aminoacyl-tRNA synthetases inhibitor with antiproliferative effect against leukaemia
Summary
Danylo Halytsky Lviv National Medical University, Ukraine https://orcid.org/0000-0002-3322-0080.
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call