4-Thiazolidinone-Bearing Hybrid Molecules in Anticancer Drug Design

Abstract

Oncological diseases have currently reached an epidemic scale, especially in industrialized countries. Such a situation has prompted complex studies in medicinal chemistry focused on the research and development of novel effective anticancer drugs. In this review, the data concerning new 4-thiazolidinone-bearing hybrid molecules with potential anticancer activity reported during the period from the years 2017–2022 are summarized. The main emphasis is on the application of molecular hybridization methodologies and strategies in the design of small molecules as anticancer agents. Based on the analyzed data, it was observed that the main directions in this field are the hybridization of scaffolds, the hybrid-pharmacophore approach, and the analogue-based drug design of 4-thiazolidinone cores with early approved drugs, natural compounds, and privileged heterocyclic scaffolds. The mentioned design approaches are effective tools/sources for the generation of hit/lead compounds with anticancer activity and will be relevant to future studies.

N-Derivatives of (Z)-Methyl 3-(4-Oxo-2-thioxothiazolidin-5-ylidene)methyl)-1H-indole-2-carboxylates as Antimicrobial Agents—In Silico and In Vitro Evaluation

“…All compounds have been assessed for their ADMET profile in ADMET Predictor version 10.4 provided by the Simulation Plus software package [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 ...…”

“…Aromatic heterocycles have been used as structural scaffolds to obtain a variety of bioactive compounds possessing antibacterial, antifungal, antiviral, and anti-parasitic activities [ 4 ]. Over the past decades, thiazolidine-2,4-diones (glitazones) have emerged as the most successful member of the 4-thiazolidinone compounds [ 5 ]. There are several drugs from this class of heterocycles, such as Lobeglitazone, Pioglitazone, Rosiglitazone, and Epalrestat, used broadly as oral anti-hyperglycemic agents for diabetes mellitus type 2 therapies, and recently, Ponesimod was approved for healing multiple sclerosis and psoriasis ( Figure 1 ).…”

Nitrogen‐Containing Heterocyclic Scaffolds as EGFR Inhibitors: Design Approaches, Molecular Docking, and Structure‐Activity Relationships

“…Additionally, docking studies also confirmed that 19 a showed the binding energy −21.8412 kcal/mol and two hydrogen bonds were created, one between the N of the quinazolidinone moiety and Lys721 and the other between the C=O of the thiazolidinone moiety and Met769. Additionally, the compound‘s planar aromatic rings created a Van der Waals connection with the amino acids Leu694, Val702, Phe699, Leu820, and Lys721 [83] …”

Synthesis, antitumor evaluation and computational study of thiazolidinone derivatives of dehydroabietic acid-based B ring-fused-thiazole

“…In addition, thiazolidinone scaffolds are privileged structures in drug design, some of its derivatives made signi cant contribution in clinical treatment [11] . In the development of antitumor agents, thiazolidinone scaffolds are also widely used as pharmacophore to form new candidate compounds, such as some synthetic indole-thiazolidinones could trigger DNA damage and induce apoptosis of human tumor cells [12] , some 2,3-disubstituted 1,3-thiazolidin-4-ones could prevent mitotic divisions of the human renal tumor cell though G1 cell cycle arrest [13] , some hybrid molecules integrated Ciminalum and thiazolidinone moieties show signi cant anticancer activity against different tumor cells [14] .…”