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In the present study, eight numbers of new 3- (4-methoxy phenyl)-5-substituted phenyl-2-pyrazoline-1-carbothioamide (5a-h) have been synthesized from 1- (4-methoxy phenyl)-3- (substituted phenyl)-prop-2-en-1-one (3a-h) and structurally characterized by using FT-IR, 1H NMR, 13C NMR, Mass and Elemental analysis. The synthesized molecules were biologically evaluated for their in vitro anticancer activity against human breast adenocarcinoma (MCF-7), liver cancer (Hep-G2) and leukaemia cancer (K-562) cell line using Sulforhodamine B (SRB) bioassay technique. From the all synthesized compounds 5a, 5c, 5d, and 5e exhibited potent anticancer activity (GI50= <10µg/ml) as compared to the controlled drug 5-Fluorouracil (5-FU) (GI50=44.5µg/ml) and Adriamycin (ADR) (GI50= <10µg/ml) on MCF-7 cell lines. Besides this, all the synthesized compounds have exhibited moderate activity against human liver cancer (Hep-G2) and leukaemia cancer (K-562) cell lines. In addition, molecular docking studies were also explored in order to study the probable binding specificity into the active site of Epidermal Growth Factor Receptor tyrosine kinase (EGFR) (PDB ID: 1M17) using Molegro Virtual Docker Evaluation 2013 6.0.1 (MVD). Based on the molecular docking result, it was found that compound 5a exhibited the best interaction with the above target (i.e., EGFR) by interacting with specific amino acid residues such as: Thr 766, Gin 767, Thr 830, Cys 575, Ala 719 and Met 769.

5-Arylidene-2,4-thiazolidinedione (5-A-TZD) is an emerging precursor molecule in medicinal chemistry for discovering multifunctional therapeutic agents. For synthesizing this precursor molecule, Knoevenagel Condensation (KC) is one of the most excellent tools in modern organic chemistry. The 5-A-TZD framework has a variety of therapeutic functions such as antidiabetic, anticancer, antimicrobial, and anti-inflammatory. As a result, several approaches and methods of KC have been established for the synthesis of this multifunctional precursor. However, the use of highly corrosive catalysts, prolonged reaction times, by-products formation, and poor product yields are the main drawbacks in 5-A-TZDs synthesis via KC. Therefore, several authors have been successfully established fast, effective, and environmentally sustainable protocols of KC using organic catalysts, inorganic catalysts, heterogeneous solid catalysts, ionic liquids (ILs), and bio-catalysts to synthesize 5-A-TZD derivatives with high conversion yield and selectivity. In this review, we have summarized the recent approaches for synthesizing 5-A-TZDs via KC and their therapeutic application as a precursor molecule in medicinal chemistry.

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