Biotechnology and Bioprocess Engineering 2019; 24(3): 464-475  
Synthesis and Biological Evaluation of New Benzylidenethiazolidine- 2,4-dione Derivatives as 15-hydroxyprostaglandin Dehydrogenase Inhibitors to Control the Intracellular Levels of Prostaglandin E2 for Wound Healing
Insun Yu1, Dubok Choi2,*, Hee-Kyung Lee3, and Hoon Cho1,*
1Department of Polymer Science & Engineering, Chosun University, Gwangju 501-759, Korea
2Biotechnology Laboratory, B-K Company Ltd, Jeonbuk 5703, Korea
3Beauty & Cosmetic Management, Business School, Seongnam 13488, CHA University, Korea
Correspondence to: Hoon Cho
Tel: +82-62-230-7635; Fax: +82-62-232-2474
E-mail: addresses: hcho@chosun.ac.kr

Dubok Choi
Tel: +82-63-466-2984; Fax: +82-63-466-2984
E-mail: addresses: choidubok@naver.com
Received: January 14, 2019; Revised: February 16, 2019; Accepted: February 17, 2019; Published online: June 30, 2019.
© The Korean Society for Biotechnology and Bioengineering. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
A novel series of benzylidenethiazolidine-2,4-dione derivatives was synthesized and investigated for 15-hydroxyprostaglandin dehydrogenase (15-PGDH)-scavenging activity, PGE2 release, and wound-healing activity. Among the tested derivatives, seven compounds (3, 9, 11, 12, 13, 14, and 25) resulted in a 50% inhibition of 15-PGDH at concentrations between 0.07 and 0.2 µM and increased PGE2 levels from 300 to over 600% in A549 cells treated with 5.0 and 10.0 µM of the compounds for 12 h. A scratch wound-healing assay using HaCaT cell line was conducted to verify the effects of 10 µM of these compounds on cell regeneration. The closure rate of the scratch wound healing showed that all compounds (3, 9, 11, 12, 13, 14, and 25) had greater wound regeneration effects than the cell growth factor, TGF-β1, which was used as the positive control. In particular, (Z)-N-benzyl-4-((2,4-dioxothiazolidin-5-ylidene)methyl)benzamide (compound 14) showed that the highest wound closure rate, which was 360%; this is about 3.6-fold higher than that of TGF-β1. Overall, these results show that compound 14 may be considered a promising candidate for the development of novel wound-healing agents.
Keywords: benzylidenethiazolidine-2,4-dione, 15-PGDH-scavenging activity, PGE2 release, wound-healing agent


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