Synthesis of withaferin a derivatives and exploratory evaluation of weight reduction and fasting blood glucose in DIO mice
- 1Pharmaceutical College, Guangxi Medical University Nanning 530021 Guangxi PR China
- 2Department of Research & Clinical Laboratory, Department of Administrative Office, The Fifth Affiliated Hospital of Guangxi Medical University, The First People's Hospital of Nanning Nanning 530022 Guangxi PR China
- 3Department of Oncology, Affiliated Hospital of YouJiang Medical University For Nationalities, Guangxi Clinical Medical Research Center for Hepatobiliary Diseases, Guangxi Higher Education Engineering Research Center for Gastrointestinal Microecology and Health, Baise City Key Laboratory of Gastrointestinal Microecology and Health Baise 533000 Guangxi PR China
Abstract
Obesity and its cardiometabolic complications remain a major public-health burden. Leptin resistance is a common feature of hyperleptinemic obesity, but the molecular basis of leptin resensitization remains incompletely understood, making the rational optimization of leptin-sensitizing agents difficult. Withaferin A (1) has been reported to enhance leptin responsiveness and to reduce body weight and the fasting blood glucose in diet-induced obese (DIO) mice. In this study, a series of withaferin A derivatives (2–15) bearing modifications in the A/B-ring region and the C-27 side-chain/lactone moiety was synthesized and evaluated in DIO mice. The compounds were administered intraperitoneally at 1.2 mg kg−1 once daily for 21 days. Withaferin A produced sustained reductions in body weight, cumulative food intake, and fasting blood glucose. Most derivatives showed weaker or less consistent responses, although compounds 2, 6, 10, and 12 significantly reduced body weight relative to the vehicle group at day 21. Overall, withaferin A (1) showed the most consistent response across the measured endpoints. These results suggest that structural modifications in either the A/B-ring region or the C-27 side-chain/lactone moiety affect the in vivo phenotypic responses of withaferin A. This study provides preliminary phenotype-level in vivo SAR information for withaferin A derivatives and may assist the design of compounds for further evaluation.
Related
- Chemical Synthesis and Immunological Evaluation of Archaeal Rare Sugar L-TalNAcA and Its Derivatives
- Design, Synthesis, and Evaluation of Novel Cephalotaxine-Cinnamic Acid Derivatives Against Hepatocellular Carcinoma
- Design, synthesis, and biological evaluation of novel 4,5-diaryl-1,2,3-thiadiazole derivatives: anticancer activity and molecular docking studies
- Design, Synthesis, In Vitro and In Silico Evaluation of Triazole–Benzimidazole Hybrid Derivatives as Potential Inhibitors of EGFR, EGFR-L858R, and EGFR-L858R/T790M
- Synthesis, RSM-based optimization, biological evaluation, and molecular modeling of novel (R)-carvone-derived isoxazole derivatives as antibacterial agents
BibTeX
@article{yan2026synthesis,
title = {{Synthesis of withaferin a derivatives and exploratory evaluation of weight reduction and fasting blood glucose in DIO mice}},
author = {Zhiming Yan and Mingming Fan and Xinyi Liang and Changhong Wei and Yiheng Zhao and Hongyu Li and Tingzhuang Yi and Shixiong Yang},
journal = {RSC Advances},
year = {2026},
month = oct,
doi = {10.1039/d6ra01511e},
url = {https://doi.org/10.1039/d6ra01511e},
note = {CC BY 3.0},
}
RIS
TY - JOUR
TI - Synthesis of withaferin a derivatives and exploratory evaluation of weight reduction and fasting blood glucose in DIO mice
AU - Zhiming Yan
AU - Mingming Fan
AU - Xinyi Liang
AU - Changhong Wei
AU - Yiheng Zhao
AU - Hongyu Li
AU - Tingzhuang Yi
AU - Shixiong Yang
PY - 2026
DA - 2026/10/09
JO - RSC Advances
DO - 10.1039/d6ra01511e
UR - https://doi.org/10.1039/d6ra01511e
AB - Obesity and its cardiometabolic complications remain a major public-health burden. Leptin resistance is a common feature of hyperleptinemic obesity, but the molecular basis of leptin resensitization remains incompletely understood, making the rational optimization of leptin-sensitizing agents difficult. Withaferin A (1) has been reported to enhance leptin responsiveness and to reduce body weight and the fasting blood glucose in diet-induced obese (DIO) mice. In this study, a series of withaferin A derivatives (2–15) bearing modifications in the A/B-ring region and the C-27 side-chain/lactone moiety was synthesized and evaluated in DIO mice. The compounds were administered intraperitoneally at 1.2 mg kg−1 once daily for 21 days. Withaferin A produced sustained reductions in body weight, cumulative food intake, and fasting blood glucose. Most derivatives showed weaker or less consistent responses, although compounds 2, 6, 10, and 12 significantly reduced body weight relative to the vehicle group at day 21. Overall, withaferin A (1) showed the most consistent response across the measured endpoints. These results suggest that structural modifications in either the A/B-ring region or the C-27 side-chain/lactone moiety affect the in vivo phenotypic responses of withaferin A. This study provides preliminary phenotype-level in vivo SAR information for withaferin A derivatives and may assist the design of compounds for further evaluation.
SN - 2046-2069
ER -