Chemoselective synthesis, X-ray structure study, Hirshfeld surface analysis, antitumor, and antimicrobial activities of new Thiophene and Thiazole derivatives

Abstract

A base-controlled chemoselective reaction of 1-phenylbutane-1,3‑dione with PhNCS and 1-chloropropan-2-one is described. Thiophene derivative 5 is obtained from the reaction in NaOEt solution, whereas thiazole 11 was isolated using potassium carbonate/DMF mixture. Spectral and X-ray structure analyses were used to characterize the synthesized compounds. Possible intermolecular interactions that control the molecular packing of the studied crystalline compounds were elucidated using Hirshfeld topology analysis. For thiophene 5, the O…H contacts are the most important and contribute to 17.7 % of the whole predicted interactions. In the case of thiazole 11, the CH…π and O…H non-covalent interactions are the most important contacts whereas the%C…H and%O…H contacts are 16.7 and 22.8 %, respectively. Additionally, there are some short H…H (47.0 %) interactions were detected where the H16A…H10A (2.165 Å) is the most important. The H…H interaction is the most dominant interaction which contributed by 47.0 and 47.0 % in 5, and 11, respectively.When compounds 5 and 11 were tested for their antimicrobial activity, the results revealed that thiophene derivative 5 has promising activity against both Salmonella SP. and Escherichia coli when compared to the standard medication gentamicin. Moreover, they were tested using the MTT assay for their antitumor activities against the colon carcinoma cell line (HCT-116) and the human hepatocellular carcinoma cell line (HepG-2). The results showed a lower cytotoxic effect against various cell lines in comparison to doxorubicin.