Synthesis, Molecular Docking and Antiproliferative Activity Studies of a Thiazole‐Based Compound Linked to Hydrazone Moiety

Abstract

(A new 4‐oxothiazolidin‐2‐ylidene derivative bearing hydrazone moiety was synthesized via Michael addition between the reaction of 4‐(4‐nitrophenyl)‐3‐thiosemicarbazide and dimethyl acetylenedicarboxylate (DMAD). The structure of synthesized compound was elucidated using various spectral techniques such as FTIR, UV‐spec, 1H NMR and 13C NMR. The structure of the related compound was confirmed by single‐crystal X‐ray analysis. Antiproliferative activity of the synthesized compound was evaluated in two human cancer cell lines, HepG2 (liver hepatocellular carcinoma cell line) and DLD‐1 (human colon cancer cell line). In addition, molecular docking of synthesized compound was investigated to give an insight of its activity against Epidermal Growth Factor Receptor tyrosine kinase domain proteins (EGFR) (lung cancer) (PDB ID: 1 M17), deleted in Liver Cancer 2 proteins (DLC2) (liver cancer) (PDB ID: 2H80), and MLK4 kinase proteins (colon cancer) (PDB ID: 4UYA) were investigated. Furthermore, the ability of the molecule to be a drug was examined by ADME/T analysis.)

Crystal structure and Hirshfeld surface analysis of 2-amino-5-{(1E)-1-[(carbamothioylamino)imino]ethyl}-4-methyl-1,3-thiazol-3-ium chloride monohydrate

“…1). A variety of thiazole derivatives are also used as target products as well as synthetic intermediates (Maharramov et al, 2011a;Kekec ¸muhammed et al, 2022).…”

Design, synthesis, molecular docking and biological evaluation of 1,2,4-triazole derivatives possessing a hydrazone moiety as anti-breast cancer agents

“…2), [11][12][13] in addition to activities against other diseases such as bacterial and fungal infections. [14][15][16][17] The bioactivity of compounds containing a hydrazone moiety is conjectured from its ability to form hydrogen bonds with molecular targets, making the compounds with this scaffold easily bind to numerous receptors and enzymes. 18 It is seen from the literature that Dandawate et al reported significant anti-breast cancer activities of hydrazone derivatives V by inhibiting NF-kB protein expression via interaction by hydrogen bonds of the hydrazone moiety and amino acid residue in p50-subunits.…”

“…21,22 One of the principal strategies for drug discovery of new drug candidates is to amalgamate two or more pharmacophoric moieties in a single molecule to achieve the synergistic effect or obtain anticancer agents via a novel mechanism of action. In light of the afore-mentioned facts and continuation of our previous studies on identifying new antiproliferative activities, 16,[23][24][25][26] hybrid compounds containing a 1,2,4-triazole ring and a hydrazone moiety were synthesized by employing an iodine mediated reaction in an attempt to get new effective anticancer molecules with increased potency (Fig. 3).…”

Synthesis, Biological Activity Evaluation and Molecular Docking of Imidazole Derivatives Possessing Hydrazone Moiety

“…[14] Also, Zhang et al reported some imidazole derivatives (3) as anti-prostate cancer agents which exhibited good anticancer activity with selectivity on health cell lines as good as clinical administered drugs. [15] Additionally, hydrazone functionality has been reported to exhibit remarkable anticancer activity, [16,17] in addition to activities against other diseases such as bacterial and fungal infections. [18,19] The bioactivity based on hydrazone moiety was hypothesized to be due to the hydrazone's capacity to process additional reactions with a class of nucleophiles such as thiol À SH and the amino À NH 2 and form hydrogen bonds with molecular targets.…”

“…Additionally, hydrazone functionality has been reported to exhibit remarkable anticancer activity, [16,17] in addition to activities against other diseases such as bacterial and fungal infections [18,19] . The bioactivity based on hydrazone moiety was hypothesized to be due to the hydrazone's capacity to process additional reactions with a class of nucleophiles such as thiol −SH and the amino −NH 2 and form hydrogen bonds with molecular targets [20] .…”