TY - JOUR
T1 - Synthesis and biological evaluation of hydroxamate isosteres of acidic cannabinoids
AU - Amin, Hawraz Ibrahim M.
AU - Ruiz-Pino, Francisco
AU - Collado, Juan A.
AU - Appendino, Giovanni
AU - Tena-Sempere, Manuel
AU - Munoz, Eduardo
AU - Caprioglio, Diego
N1 - Publisher Copyright:
Copyright © 2023 Amin, Ruiz-Pino, Collado, Appendino, Tena-Sempere, Munoz and Caprioglio.
PY - 2023
Y1 - 2023
N2 - Despite their early discovery, the bioactivity of acidic cannabinoids was long overlooked. Issues of stability and a pharmacological focus on Δ9-THC and its biological profile combined to relegate the non-narcotic native form of phytocannabinoids to a sort of investigational limbo. Recent studies have disclosed an attractive bioactivity profile for specific acidic phytocannabinoids but concerns about their limited stability have remained substantially unaddressed. To solve this issue, we have developed the hydroxamate derivatives of Δ8-tetrahydrocannabinolic acid-A (Δ8-THCA-AH, 6) and cannabidiolic acid (CBDAH, 5) as novel acidic cannabinoid bioisosteres, and we report here their synthesis and bioactivity profile against specific cannabinoid targets, as well as promising in vivo activity in a murine model of polycystic ovary syndrome (PCOS) associated with obesity.
AB - Despite their early discovery, the bioactivity of acidic cannabinoids was long overlooked. Issues of stability and a pharmacological focus on Δ9-THC and its biological profile combined to relegate the non-narcotic native form of phytocannabinoids to a sort of investigational limbo. Recent studies have disclosed an attractive bioactivity profile for specific acidic phytocannabinoids but concerns about their limited stability have remained substantially unaddressed. To solve this issue, we have developed the hydroxamate derivatives of Δ8-tetrahydrocannabinolic acid-A (Δ8-THCA-AH, 6) and cannabidiolic acid (CBDAH, 5) as novel acidic cannabinoid bioisosteres, and we report here their synthesis and bioactivity profile against specific cannabinoid targets, as well as promising in vivo activity in a murine model of polycystic ovary syndrome (PCOS) associated with obesity.
KW - PPAR γ
KW - acidic cannabinoids
KW - cannabinoid receptors
KW - hydroxamates
KW - obesity
UR - https://www.scopus.com/pages/publications/105016399078
U2 - 10.3389/fntpr.2023.1190053
DO - 10.3389/fntpr.2023.1190053
M3 - Article
SN - 2813-2602
VL - 2
JO - Frontiers in Natural Products
JF - Frontiers in Natural Products
M1 - 1190053
ER -
