C19 trityl and silyl andrographolide analogs exhibit in vitro anticancer activity in murine cancer models
- 1Department of Chemistry, Aspiring Scholars Directed Research Program
Abstract
Andrographolide, a labdane diterpenoid isolated from A. paniculata has been investigated for activity in a broad panel of biological contexts, including its anti-inflammatory, antiviral, and anticancer properties. Previously, A-ring analogs of andrographolide bearing silyl and trityl ethers at C19 have demonstrated improved in vitro anticancer activity in human cancer cell lines, with putative activity through the Wnt1/{beta}-catenin signaling axis. In order to investigate the activity of this series of C19 andrographolide analogs, alongside a cyclic A-ring acetonide analog, as anticancer agents in murine cancer cell models, we evaluated antiproliferative activity of these compounds in B16F10 melanoma, CT26 colorectal adenocarcinoma, Neuro2a neuroblastoma, and 4T1 mammary ductal carcinoma cell lines, and found that most compounds exhibited potent micromolar level anticancer activity. Among these, all trityl ethers exhibited nearly indistinguishable IC50 values of 4-20 M, and generally exhibited greater potency compared to C19 silyl ether analogs. This anticancer activity was further validated through apoptosis flow cytometry, wherein we concluded that our compounds induced apoptosis to a greater extent than the parent compound, andrographolide. Further, we examine the role of modulation of canonical Wnt1/{beta}-catenin signaling in a series of co-delivery assays with CHIR-99021, a selective GSK-3{beta} kinase inhibitor, and MSAB, a selective {beta}-catenin degrader. Finally, we demonstrate that a selection of silyl ether analogs of andrographolide elicit cell cycle arrest by flow cytometry in a manner that is decoupled to in vitro potency trends. Altogether, we report the first in vitro evaluation of trityl and silyl ether analogs of andrographolide within murine adherent cancer cells.
Related
- Stereoselective Synthesis of 12( R )-Hydrazineyl-14-deoxy Andrographolide Analogues and Their Cytotoxic Activity
- Andrographolide Promotes Post-Ischemic Endothelial Angiogenic Activity via IL-10-Mediated M2-Like Microglia-Endothelial Crosstalk Involving Endothelial VEGFR2 Upregulation.
- Extracts of Bacillus proteolyticus strain OSUB18 exhibit cytostatic activity
- Development and characterization of an Eugenol–Shilajit–Chitosan nano-gel composite with anticancer activity against oral squamous cell carcinoma
- Ethnopharmacological evaluation of Irvingia gabonensis (Aubry-Lecomte ex O'Rorke) Baill. seed extract: integrated computational and in vitro assessment of antioxidant, antidiabetic, and anticancer activities with in vivo validation of antidiabetic activity
BibTeX
@misc{raval2026trityl,
title = {{C19 trityl and silyl andrographolide analogs exhibit in vitro anticancer activity in murine cancer models}},
author = {R. Raval and R. Liu and A. Pak and A. X. Yee and S. Venkatesh and L. Lam and A. Hothi and L. Chen and A. Yu and H. Seto and C. Casal Montserrat and F. Wang-Johanning and G. Johanning and E. Njoo},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.27.762108},
url = {https://www.biorxiv.org/content/10.64898/2026.10.27.762108v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - C19 trityl and silyl andrographolide analogs exhibit in vitro anticancer activity in murine cancer models
AU - R. Raval
AU - R. Liu
AU - A. Pak
AU - A. X. Yee
AU - S. Venkatesh
AU - L. Lam
AU - A. Hothi
AU - L. Chen
AU - A. Yu
AU - H. Seto
AU - C. Casal Montserrat
AU - F. Wang-Johanning
AU - G. Johanning
AU - E. Njoo
PY - 2026
DA - 2026/10/27
PB - bioRxiv
DO - 10.64898/2026.10.27.762108
UR - https://www.biorxiv.org/content/10.64898/2026.10.27.762108v1
AB - Andrographolide, a labdane diterpenoid isolated from A. paniculata has been investigated for activity in a broad panel of biological contexts, including its anti-inflammatory, antiviral, and anticancer properties. Previously, A-ring analogs of andrographolide bearing silyl and trityl ethers at C19 have demonstrated improved in vitro anticancer activity in human cancer cell lines, with putative activity through the Wnt1/{beta}-catenin signaling axis. In order to investigate the activity of this series of C19 andrographolide analogs, alongside a cyclic A-ring acetonide analog, as anticancer agents in murine cancer cell models, we evaluated antiproliferative activity of these compounds in B16F10 melanoma, CT26 colorectal adenocarcinoma, Neuro2a neuroblastoma, and 4T1 mammary ductal carcinoma cell lines, and found that most compounds exhibited potent micromolar level anticancer activity. Among these, all trityl ethers exhibited nearly indistinguishable IC50 values of 4-20 M, and generally exhibited greater potency compared to C19 silyl ether analogs. This anticancer activity was further validated through apoptosis flow cytometry, wherein we concluded that our compounds induced apoptosis to a greater extent than the parent compound, andrographolide. Further, we examine the role of modulation of canonical Wnt1/{beta}-catenin signaling in a series of co-delivery assays with CHIR-99021, a selective GSK-3{beta} kinase inhibitor, and MSAB, a selective {beta}-catenin degrader. Finally, we demonstrate that a selection of silyl ether analogs of andrographolide elicit cell cycle arrest by flow cytometry in a manner that is decoupled to in vitro potency trends. Altogether, we report the first in vitro evaluation of trityl and silyl ether analogs of andrographolide within murine adherent cancer cells.
ER -