Thiazolidinone motif in anticancer drug discovery. Experience of DH LNMU medicinal chemistry scientific group

R B Lesyk,D Ya Havryluk,B S Zimenkovsky,I Yu Subtel'Na,D V Atamanyuk,A P Kryshchyshyn,D V Khyluk,D V Kaminskyy

doi:10.7124/bc.000089

Abstract

Keywords: synthesis, 4-thia(imida)zolidinones, thiopyrano[2,3-d]thiazoles, anticancer activity, (Q)SAR

Highlights

Thiazolidinone derivatives are well known class of biological active substances [1,2,3] that became basic for the whole number of innovative medicinal agents, such as hypoglycemic thiazolidinediones (Pioglitazone and its analogues) [4], aldose reductase inhibitors (Epalrestat) [5], dual inhibitors of COX-2/5-LOX (Darbufelon) [6], modern diuretics (Etozoline) [7], Mur family inhibitors (UDP-MurNAc/ L-Ala ligases) etc. [8]
Inhibitors of antiapoptotic proteins Bcl-XL and ВН3 [11] which contribute to modulation of programmed cell death, as well as inhibitors of tumor necrosis factor TNFa [12], necroptosis inhibitors [13], integrin antagonists [14], inhibitors of JSP-1 [15], Pim-2 and Рim-1 protein kinases [16], COX-2 [17] etc. were identified among 4-thiazolidinones
While applying the research strategy through the past few years we succeeded in gaining a number of interesting synthetic results that make possible to extend the field of the chemistry of thiazolidinone and related heterocycles, especially in the scope of «drug-like» molecules design

Summary

Introduction

Thiazolidinone derivatives are well known class of biological active substances [1,2,3] that became basic for the whole number of innovative medicinal agents, such as hypoglycemic thiazolidinediones (Pioglitazone and its analogues) [4], aldose reductase inhibitors (Epalrestat) [5], dual inhibitors of COX-2/5-LOX (Darbufelon) [6], modern diuretics (Etozoline) [7], Mur family inhibitors (UDP-MurNAc/ L-Ala ligases) etc. [8]. Thiazolidinone derivatives are well known class of biological active substances [1,2,3] that became basic for the whole number of innovative medicinal agents, such as hypoglycemic thiazolidinediones (Pioglitazone and its analogues) [4], aldose reductase inhibitors (Epalrestat) [5], dual inhibitors of COX-2/5-LOX (Darbufelon) [6], modern diuretics (Etozoline) [7], Mur family inhibitors (UDP-MurNAc/ L-Ala ligases) etc. Thiazolidinone research area unexpectedly became interesting and promising for oncology. Biological active thiazolidinones and related heterocycles refer to one of the most successful scientific projects in the area of pharmacy of DH LNMU (Fig. 1). It is based on three strategic vectors: а) organic synthesis; b) pharmacological research; c) rational design of «drug-like» molecules (virtual screening: QSARanalysis, molecular docking etc.) [1, 18]

Objectives

Results

Conclusion