New thiazole derivatives: Synthesis, X-ray crystal structure, Hirshfeld surface analysis, and biological evaluations as potential antimicrobial and antitumor agents

Abstract

Thiazole ring has a wide range of biological activities which is proven by its presence in more than eighteen FDA-approved drugs in addition to several compounds that are currently under clinical investigation. Substitution of the thiazole ring at positions 2,4, and 5 led to new derivatives with potent biological activities. Interestingly, the bromination of ethyl 2-cyano-2-(4-methyl-3-phenylthiazol-2(3H)-ylidene)acetate (1) in acetic acid afforded (Z)-ethyl 2-(5‑bromo-4-(bromomethyl)-3-phenylthiazol-2(3H)-ylidene)-2-cyanoacetate (2) instead of the expected bromomethyl derivative 3. The reaction of thiazole derivative 2 with p-anisidine or aniline produced the corresponding thiazole derivatives 5a,b. The synthesized compounds were characterized based on their spectral and elemental data. Moreover, the structure of compound 2 was determined through X-ray crystallography. The molecular structure of 2 was crystallized in the orthorhombic, Pna21, a = 15.8144 (6) Å, b= 9.0238 (4) Å, c = 11.3296 (4) Å, V = 1616.80 (11) Å3, Z = 4. Analysis of the dnorm map and fingerprint plot for all possible intermolecular interactions in the crystal structure of thiazole 2 indicated the importance of the Br…O, O…H, and Br…H interactions in the molecular packing. The O1…H14A (2.548 Å), Br1…O1 (3.211 Å) and Br2…H7B (2.931 Å) interactions are the most short contacts. In addition, the percentages of the Br…O, O…H, and Br…H contacts are 2.3, 10.3 and 22.1 %, respectively. The antimicrobial activity of thiazole derivative 5a was tested, and the results revealed that it is equipotent to both Ampicillin against Staphylococcus aureus and to Gentamycin against Salmonella SP. In comparison to Doxorubicin, thiazole 5a showed less antitumor activity against the hepatocellular carcinoma (HepG-2) and colon carcinoma (HCT-116) cell lines.