Table 1.
Approaches in optimizing oridonin.
| Modified Structure/Name of Compounds | Chemical Structures | Targeting Pathways | Models Tested | Ref |
|---|---|---|---|---|
| Oridonin |  |
1 | ||
| 1-O- and 14-O-derivatives |  |
– | BGC-7901, SW-480, HL-60, BEL-7402, A549, B16 | 50 |
| Ent-6,7-seco-oridonin derivatives |  |
– | A549, Bel-7402, K562, MGC-803, CaEs-17 | 52 |
| 13p |  |
Mitochondrial pathway | MCF-7 | 53 |
| DS2 |  |
MMP, ROS | EC9706, EC109, HEECs, HL-7702 | 54 |
| Geridonin |  |
ROS-mediated PTEN, PI3K/Akt pathway | MGC 803 | 55,56 |
| Furoxan-based nitric oxide-releasing derivative |  |
– | Bel-7402, K562, MGC-803, CaEs-17 | 57 |
| Spirolactone-type diterpenoid derivatives |  |
– | Bel-7402, K562, MGC-803, CaEs-17 | 58 |
| Enmein-type diterpenoid analogs |  |
Mitochondria-related caspase-dependent pathway | Bel-7402, K562, MGC-803, CaEs-17 | 59 |
| H2S releasing ent-kaurane diterpenoid oridonin derivatives |  |
Extrinsic and intrinsic apoptosis pathways | HepG2, MCF-7, HCT-116, B16, K562, L-02, PBMC |
60 |
| Nitric oxide (NO)-releasing oridonin derivatives |  |
Apoptosis and cell cycle arrest at S phase | Bel-7402 | 63 |
| Seven-membered C-ring-expanded 6,7-seco-ent-kaurenes |  |
Apoptosis and cell cycle arrest | MCF-7 | 64 |
| Enmein-type diterpenoid amino acid ester derivatives |  |
Intrinsic apoptosis pathway | Bel-7402, SGC-7901, HL-60, PC-3, A549, K562, L-02 | 66 |
| Ent-kaurane and spirolactone-type 6,7-seco-ent-kaurane derivatives |  |
Intrinsic apoptosis pathway | K562, Bel-7402, SGC-7901, A549, L-02, PBMC |
67 |
| A-ring nitrogen-enriched modifications |  |
Mitochondria-dependent pathway; antifibrosis through NF-κB pathway; STAT3 |
MDA-MB-232, MCF-7, MCF-7/ADR, HMEC, LX-2, HSC-T6, A2780, OVCAR3, OVCAR8, SKOV3 |
68-70, 78, 79 |
| CYD-6-17 (CYD0617) |  |
Wnt/β-catenin pathway | T24-P, UMUC3 | 71 |
| AKT/PDPK1 | 786-0 KD, HK-2 KD resistant to mTOR and tyrosine kinase inhibitors | 72 | ||
| D-ring modifications |  |
NRF-2/RHOA/ROCK signaling pathway | MDA-MB-231, GI101, GILM2, GILM3 | 74 |
| Oridonin A-ring-based diverse constructions of enone functionality |  |
p53-dependent apoptosis | LX-2 cells | 73, 76 |
| α-formylenone in the A-ring and introduction of an acetonide moiety to 7,14-dihydroxyl |  |
S-phase cell cycle arrest, apoptosis | LX-2 cells | 77 |
| HAO472, prodrug with an amino acid residue |  |
Suppressing NF-κB pathway | mouse colitis model | 5 |
| Benzene analogues at C17 position |  |
– | AGS, MGC803, Bel7402, HCT116, A549, HeLa cells | 81 |
| 14-substituted oridonin analogs |  |
p53-MDM2 pathway | HCT116, BEL7402, MCF-7 | 82 |