Synthesis, Structural Analysis, and Biological Evaluation of Novel ((2,4-dioxothiazolidin-5-ylidene)methyl)phenyl Derivatives

• Published in: Biotechnology and bioprocess engineering 2020, 25(2), , pp.149-163
• Main Authors: Na, A Ri, Choi, Dubok, Cho, Hoon
• Format: Article
• Language: English
• Subjects: Amino acids; Biological effects; Biotechnology; Chemistry; Chemistry and Materials Science; Derivatives; Enzymes; Gene expression; Homeostasis; Industrial and Production Engineering; Inflammation; Inflammatory diseases; Kinases; Neutrophils; Physiology; Prostaglandin E2; Regeneration; Research Paper; Signal transduction; Structural analysis; Synthesis; Wound healing; 생물공학
• ISSN: 1226-8372; 1976-3816
• DOI: 10.1007/s12257-019-0308-y

The objective of this study was to evaluate the synthesis, structural analysis, and biological effects of novel ((2, 4-dioxothiazolidin-5-ylidene)methyl)phenyl derivatives. The efficacy of 15-PGDH inhibition increased for the substituents in the derivatives in the order: cyclohexylpropyl > cyclohexylethyl > cyclohexylmethyl > cyclohexyl. Compound 12 inhibited 15-PGDH activity by binding to the amino acids Ile 214, Ile 210, Ile 194, Gln 148, and Leu 191 of 15-PGDH. Compounds 4, 22 , and 23 produced the highest increment in PGE 2 concentration, which was 122.19, 100.14, and 206.80%, respectively, compared to that of the control. Also, compounds 38 and 39 , in which the central phenyl ring and the 2, 4-thiazolidinedione moiety were linked by a single bond, produced a relatively high increment in PGE 2 concentration, which was 106.81 and 118.66%, respectively, compared to that of the control. The wound closure rates of compounds 22 and 39 were the highest, being 247.56 and 202.42%, respectively, compared to that of the positive control. Therefore, compounds 22 and 39 could not only efficiently regulate PGE 2 concentration, but also induce cellular regeneration, and are expected to effectively treat a variety of diseases resulting from PGE 2 deficiency.