CAPE derivatives: Multifaceted agents for chronic wound healing.

Autor: Balaha M; Department of Pharmacy, 'G. d'Annunzio' University of Chieti-Pescara, Chieti, Italy.; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Kafrelsheikh University, Kafr el-Sheikh, Egypt., Cataldi A; Department of Pharmacy, 'G. d'Annunzio' University of Chieti-Pescara, Chieti, Italy., Ammazzalorso A; Department of Pharmacy, 'G. d'Annunzio' University of Chieti-Pescara, Chieti, Italy., Cacciatore I; Department of Pharmacy, 'G. d'Annunzio' University of Chieti-Pescara, Chieti, Italy., De Filippis B; Department of Pharmacy, 'G. d'Annunzio' University of Chieti-Pescara, Chieti, Italy., Di Stefano A; Department of Pharmacy, 'G. d'Annunzio' University of Chieti-Pescara, Chieti, Italy., Maccallini C; Department of Pharmacy, 'G. d'Annunzio' University of Chieti-Pescara, Chieti, Italy., Rapino M; Genetic Molecular Institute of CNR, Unit of Chieti, 'G. d'Annunzio' University of Chieti-Pescara, Chieti, Italy., Korona-Glowniak I; Department of Pharmaceutical Microbiology, Medical University of Lublin, Lublin, Poland., Przekora A; Department of Tissue Engineering and Regenerative Medicine, Medical University of Lublin, Lublin, Poland., di Giacomo V; Department of Pharmacy, 'G. d'Annunzio' University of Chieti-Pescara, Chieti, Italy.; UdA-TechLab, Research Center, University 'G. d'Annunzio' of Chieti-Pescara, Chieti, Italy.
Jazyk: angličtina
Zdroj: Archiv der Pharmazie [Arch Pharm (Weinheim)] 2024 Oct; Vol. 357 (10), pp. e2400165. Date of Electronic Publication: 2024 Jul 25.
DOI: 10.1002/ardp.202400165
Abstrakt: Chronic wounds significantly impact the patients' quality of life, creating an urgent interdisciplinary clinical challenge. The development of novel agents capable of accelerating the healing process is essential. Caffeic acid phenethyl ester (CAPE) has demonstrated positive effects on skin regeneration. However, its susceptibility to degradation limits its pharmaceutical application. Chemical modification of the structure improves the pharmacokinetics of this bioactive phenol. Hence, two novel series of CAPE hybrids were designed, synthesized, and investigated as potential skin regenerative agents. To enhance the stability and therapeutic efficacy, a caffeic acid frame was combined with quinolines or isoquinolines by an ester (1a-f) or an amide linkage (2a-f). The effects on cell viability of human gingival fibroblasts (HGFs) and HaCaT cells were evaluated at different concentrations; they are not cytotoxic, and some proved to stimulate cell proliferation. The most promising compounds underwent a wound-healing assay in HGFs and HaCaT at the lowest concentrations. Antimicrobial antioxidant properties were also explored. The chemical and thermal stabilities of the best compounds were assessed. In silico predictions were employed to anticipate skin penetration capabilities. Our findings highlight the therapeutic potential of caffeic acid phenethyl ester (CAPE) derivatives 1a and 1d as skin regenerative agents, being able to stimulate cell proliferation, control bacterial growth, regulate ROS levels, and being thermally and chemically stable. An interesting structure-activity relationship was discussed to suggest a promising multitargeted approach for enhanced wound healing.
(© 2024 Deutsche Pharmazeutische Gesellschaft.)
Databáze: MEDLINE
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