Synthesis, distribution analysis and mechanism studies of N-acyl glucosamine-bearing oleanolic saponins

Targeting Colorectal Cancer with Conjugates of a Glucose Transporter Inhibitor and 5-Fluorouracil

“…Compounds 4 – 9 , 16 – 17 , and 5-FU were evaluated for their cytotoxicity against the CRC cell lines HCT-116 and HT-29 (both of which overexpress GLUT1, Figure S50) using the sulforhodamine B (SRB) assay (Table ). − 5-FU exhibited an IC 50 of approximately 15 μM in CRC cells (entry 1, Table ). To mimic the tumor microenvironment, 10 mM GSH was first attempted to add to the medium; however, we found that 10 mM GSH interfered CRC cell growth.…”

Biological and Pharmacological Effects of Synthetic Saponins

“…The in vivo mice study revealed the tumor regression activity in H22 xenograft and MCF-7 xenograft models. The proposed anticancer cytotoxicity pathways in oleanane-saponin involved mitochondrial-dependent intrinsic apoptosis [31,35], apoptosis-ferroptosis-M2-TAM polarization [30], PI3K/Akt/mTOR pathway [21], and G1 cell cycle arrest [45]. Lupane-saponins were found to exhibit in vitro antitumor cytotoxicity in IC 50 = 0.9-5.0 µM in colorectal cancer (DLD-1), breast cancer (MCF-7), leukemia (CEM), cervical cancer (HeLa), and melanoma (G-361); >100 and 1.3 µM in normal WS-1 and BJ cells, respectively.…”

“…Synthetic oleanolic saponins (Figure 2) have been evaluated on their antitumor [14,18,21,[29][30][31][32][33][34][35][36][37], anti-Alzheimer [38], antiviral [39,40], antiglucosidase [41], immunomodulating [42], and detoxification [43] activities (Table 1). Yang and co-workers reported a series of structures derivatized from potent antitumor Pulsatilla saponins, hederacolchiside A and D, elucidating the selectivity between the antitumor activity and hemolytic toxicity of compounds.…”

“…To further elucidate the mechanism of our compound in causing HL-60 cell death, we applied the Annexin V/DRAQ5 assay to identify the apoptosis-triggering effect, and the cell cycle analysis found that HL-60 cancer cells were arrested in the sub-G1 phase in a dose-dependent manner. Combining the results of western blotting and stable isotope labeling by/with amino acids in cell culture (SILAC) proteomics, glucosamine-bearing oleanolic saponin was found to trigger both intrinsic and extrinsic apoptosis and inhibit the PI3K/Akt/mTOR pathway in HL-60 cancer cells [21].…”

“…The synthetic methods of saponins have been well reviewed, providing complete information on the organic synthesis to perform SAR optimization [6,7]. Based on the research experiences on carbohydrate [8,9] and medicinal [10][11][12][13][14][15][16][17][18][19][20][21][22] chemistry in our lab, we summarize the biological effects and preliminary SAR results of synthetic saponins over the last five years to serve as a bridge between chemistry and biology, providing an insight for further structure optimization and mechanism studies, finally facilitating the development of saponin-based bioactive compounds.…”