Synthesis, Molecular Docking Study, and Cytotoxicity Evaluation of Some Novel 1,3,4-Thiadiazole as Well as 1,3-Thiazole Derivatives Bearing a Pyridine Moiety

Abstract

Pyridine, 1,3,4-thiadiazole, and 1,3-thiazole derivatives have various biological activities, such as antimicrobial, analgesic, anticonvulsant, and antitubercular, as well as other anticipated biological properties, including anticancer activity. The starting 1-(3-cyano-4,6-dimethyl-2-oxopyridin-1(2H)-yl)-3-phenylthiourea (2) was prepared and reacted with various hydrazonoyl halides 3a–h, α-haloketones 5a–d, 3-chloropentane-2,4-dione 7a and ethyl 2-chloro-3-oxobutanoate 7b, which afforded the 3-aryl-5-substituted 1,3,4-thiadiazoles 4a–h, 3-phenyl-4-arylthiazoles 6a–d and the 4-methyl-3- phenyl-5-substituted thiazoles 8a,b, respectively. The structures of the synthesized products were confirmed by spectral data. All of the compounds also showed remarkable anticancer activity against the cell line of human colon carcinoma (HTC-116) as well as hepatocellular carcinoma (HepG-2) compared with the Harmine as a reference under in vitro condition. 1,3,4-Thiadiazole 4h was found to be most promising and an excellent performer against both cancer cell lines (IC50 = 2.03 ± 0.72 and 2.17 ± 0.83 µM, respectively), better than the reference drug (IC50 = 2.40 ± 0.12 and 2.54 ± 0.82 µM, respectively). In order to check the binding modes of the above thiadiazole derivatives, molecular docking studies were performed that established a binding site with EGFR TK.

Synthesis, Biological Evaluation, and Molecular Docking of Novel Azolylhydrazonothiazoles as Potential Anticancer Agents

“…All minimizations were performed until a root mean square deviation (RMSD) gradient 0.01 kcal·mol –1 Å –1 using MMFF 94× (Merck molecular force field 94×), and the partial charges were determined automatically. The binding affinity of the ligand was evaluated using the scoring function and dock function (S, Kcal/mol) created by the MOE software. , The screened compounds and the co-crystallized inhibitor (W19) were prepared for the docking process toward (EGFR TK) by importing them into one database and storing them as an MDB file. From the Protein Data Bank (), the (EGFR TK) X-ray was retrieved .…”

“…The binding affinity of the ligand was evaluated using the scoring function and dock function (S, Kcal/mol) created by the MOE software. 48,49 The screened compounds and the co-crystallized inhibitor (W19) were prepared for the docking process toward (EGFR TK) by importing them into one database and storing them as an MDB file. From the Protein Data Bank (https://www.rcsb.org/structure/3W33), the (EGFR TK) X-ray was retrieved.…”

Synthesis and Molecular Docking of Some Novel 3-Thiazolyl-Coumarins as Inhibitors of VEGFR-2 Kinase

“…In light of our previous work on the synthesis of novel antitumor heterocycles [ 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 ] and with consideration of the aforementioned results, a new sort of VEGFR-2 inhibitors has been developed as prospective anti-breast cancer agents by hybridizing the coumarin and 1,3-thiazole moieties, which have been found to inhibit kinases and have antiproliferative properties. In this study, we developed and synthesized new 3-thiazolhydrazinylcoumarins in an effort to enhance the target compounds’ synergistic pharmacological significance and assess their anti-breast cancer activity targeting VEGFR-2.…”

Fluorenone–thiazolidine-4-one scaffolds as antidiabetic and antioxidant agents: design, synthesis, X-ray crystal structures, and binding and computational studies

“…1) have been found to be powerful PPARδ agonists and α-glucosidase inhibitors for the treatment of T2DM. The widespread use of the thiazolidine-4-one ring, on the other hand, has exhibited a wide range of biological activities including anticancer, 9–13 anti-tuberculosis, 14 antiviral, 15 antimicrobial, 16 antimycobacterial, 17 and anti-HIV. 18,19…”