TY - JOUR
T1 - Selected N-terpenyl Organoselenium Compounds Possess Antimycotic Activity In Vitro and in a Mouse Model of Vulvovaginal Candidiasis
AU - Liang, Xiuyi
AU - Pacuła-Miszewska, Agata J.
AU - Obieziurska-Fabisiak, Magdalena
AU - Vartak, Richa
AU - Mao, Ganming
AU - Patel, Ketankumar
AU - Fedosova, Natalya
AU - Ścianowski, Jacek
AU - Billack, Blase
PY - 2023/11
Y1 - 2023/11
N2 - In the present work, a series of N-terpenyl organoselenium compounds (CHB1-6) were evaluated for antimycotic activity by determining the minimum inhibitory concentration (MIC) for each compound in fluconazole (FLU)-sensitive (S1) and FLU-resistant (S2) strains of Candida albicans (C. albicans). The most active compounds in the MIC screen were CHB4 and CHB6, which were then evaluated for cytotoxicity in human cervical cancer cells (KB-3-1) and found to be selective for fungi. Next, CHB4 and CHB6 were investigated for skin irritation using a reconstructed 3D human epidermis and both compounds were considered safe to the epidermis. Using a mouse model of vulvovaginal candidiasis (VVC), CHB4 and CHB6 both exhibited antimycotic efficacy by reducing yeast colonization of the vaginal tract, alleviating injury to the vaginal mucosa, and decreasing the abundance of myeloperoxidase (MPO) expression in the tissue, indicating a reduced inflammatory response. In conclusion, CHB4 and CHB6 demonstrate antifungal activity in vitro and in the mouse model of VVC and represent two new promising antifungal agents.
AB - In the present work, a series of N-terpenyl organoselenium compounds (CHB1-6) were evaluated for antimycotic activity by determining the minimum inhibitory concentration (MIC) for each compound in fluconazole (FLU)-sensitive (S1) and FLU-resistant (S2) strains of Candida albicans (C. albicans). The most active compounds in the MIC screen were CHB4 and CHB6, which were then evaluated for cytotoxicity in human cervical cancer cells (KB-3-1) and found to be selective for fungi. Next, CHB4 and CHB6 were investigated for skin irritation using a reconstructed 3D human epidermis and both compounds were considered safe to the epidermis. Using a mouse model of vulvovaginal candidiasis (VVC), CHB4 and CHB6 both exhibited antimycotic efficacy by reducing yeast colonization of the vaginal tract, alleviating injury to the vaginal mucosa, and decreasing the abundance of myeloperoxidase (MPO) expression in the tissue, indicating a reduced inflammatory response. In conclusion, CHB4 and CHB6 demonstrate antifungal activity in vitro and in the mouse model of VVC and represent two new promising antifungal agents.
KW - Candida albicans
KW - Candida resistant strains
KW - N-terpenyl organoselenium
KW - antifungal activity
KW - vulvovaginal candidiasis
KW - Microbial Sensitivity Tests
KW - Fluconazole/pharmacology
KW - Humans
KW - Candidiasis, Vulvovaginal/drug therapy
KW - Antifungal Agents/metabolism
KW - Vagina/microbiology
KW - Female
UR - http://www.scopus.com/inward/record.url?scp=85176560781&partnerID=8YFLogxK
U2 - 10.3390/molecules28217377
DO - 10.3390/molecules28217377
M3 - Journal article
C2 - 37959796
SN - 1420-3049
VL - 28
JO - Molecules (Basel, Switzerland)
JF - Molecules (Basel, Switzerland)
IS - 21
M1 - 7377
ER -