IN SILICO SEARCH FOR BIOLOGICALLY ACTIVE CHEMICAL COMPOUNDS AMONG 5-ARYLIDENE SUBSTITUTED DERIVATIVES OF RHODANINE WITH BENZOTHIAZOLE MOIETY IN THE MOLECULES

Background. Knowledge about biological targets is important for effective treatment of diseases. The development of computer technology has led the emergence of a number of web tools that can help in this at the initial stages of drug development. Based on the known pharmacological potential of benzotiazole-substituted rhodanines and using modern virtual screening tools, we have carried out a targeted search for biologically active molecules among 5-arylidene substituted rhodanines with a benzothiazole moiety in molecules. The effect of various aryl substituents on the inhibitory activity of series compounds to therapeutic targets has been studied. Aim: to evaluate the potential pharmacological activity 5-arylidene derivatives of N-(4-oxo-2-thioxothiazolidin-3-yl)-2-(2-oxobenzo[d]thiazol-3(2H)-yl) acetamide using a virtual computer program. Material and methods. A series of 5-arylidene derivatives of 2- thioxothiazolidin-4-one (rhodanine) with 2-oxobenzothiazole moeity at the position 3 of the core heterocycle was investigated using the freely available program SuperPred 3.0. Virtual screening of derivatived was performed to identify potential biologically active compounds. Results. Derivatives with different arylidene substituents at the position 5 of the core heterocycle demonstrated a high probability of interaction with multiple targets. The common predicted targets for the compounds with the highest binding scores and model accuracy are Aldose reductase, Transcription intermediary factor 1-alpha and Cathepsin D. The highest binding scores with targets are attributed to compounds 3 (97,49% interaction with Transcription intermediary factor 1-alpha), 5 (98,42% interaction with Aldose reductase) і 9 (98,39% interaction with Cathepsin D). The prediction accuracy for these target models is sufficiently high at 95,56%, 92,38%, and 98,95%, respectively. Conclusion. Among the broad spectrum of probable types of biological activity of the investigated compounds, antitumor activity is predominant. We consider compound 8 to be the most promising derivative with a probable effect on tumor targets. The “structute – activity” analysis revealed an important role of 5-ene substituent of the core rhodanine scaffold in ensuring affinity for these biotargents. The effect of 5-arylidene derivatives on the corresponding protein molecules is higher than predicted for the core compound. The date obtained require further experimental confirmation.