Efficient Synthesis and Evaluation of Novel Sulfonated Dihydropyrimidinthione Derivatives for the Treatment of UV‐B‐Induced Corneal Damage

• Published in: Photochemistry and photobiology Vol. 99; no. 4; pp. 1149 - 1156
• Main Authors: Du, Enming, Jiang, Yueping, Qin, Fangyuan, Wang, Yange, He, Siyu, Wang, Gang, Song, Zongming, Zhang, Junjie, Tao, Ye
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.07.2023
• Subjects: Anti-Inflammatory Agents - pharmacology; Apoptosis; Biocompatibility; Caspase; Cell viability; Cornea; Corneal Injuries; DNA damage; Drug development; Humans; Inflammation; Radiation damage; Signal Transduction; Ultraviolet Rays
• ISSN: 0031-8655; 1751-1097
• DOI: 10.1111/php.13748

UV‐B‐induced corneal damage remains a challenge in clinics, and it is needed to develop novel and effective medicines against UV‐B induced photodamage. 3,4‐Dihydropyrimidine‐2(1H)‐thione derivatives have shown many interesting biological activities, including antibacterial, anti‐inflammatory, antioxidant, etc. In order to find a promising anticorneal photodamage agent, we designed and synthesized two novel sulfonated dihydropyrimidinthione derivatives to evaluate cytoprotective effect against UV‐B‐mediated photodamage. With simple structure, compound 6 possessed good water solubility, photostability and biocompatibility. We demonstrated that 6 exhibited significant cytoprotective effects against UV‐B‐mediated photodamage and the cell viability was up to 93% at 0.2 mg mL−1. The corneal cells were highly sensitive to UV‐B radiation, resulting in the release of inflammatory mediators and DNA damage, which were significantly reversed by 6. Moreover, compound 6 reduced Bax and cleaved Caspase‐3 expressions to suppress UV‐B mediated the intrinsic apoptosis pathway. Our findings suggest that 6 is a promising UV‐B resistant agent with potential to be a promising drug candidate for the treatment of corneal photodamage. UV‐B‐induced corneal damage remains a challenge in clinics. In this work, we designed and synthesized two novel sulfonated dihydropyrimidinthione derivatives to evaluate cytoprotective effect against UV‐B‐mediated photodamage. With simple structure, compound 6 possessed good water solubility, photostability and biocompatibility. Especially, compound 6 exhibited significant cytoprotective effects against UV‐B‐mediated photodamage and the cell viability was up to 93% at 0.2 mg mL−1, versus 22% of UV‐B radiation. Our findings suggest that 6 is a promising UV‐B resistant agent with potential to be a promising drug candidate for the treatment of corneal photodamage.