| Description: |
Camptothecin is a specific inhibitor of DNA topoisomerase I (Topo I) with IC50 of 0.68 μM; it is a novel alkaloidal leukemia and tumor inhibitor, is a strong inhibitor of nucleic acid synthesis in mammalian cells and a potent inducer of strand breaks in chromosomal DNA. Camptothecin and its analogs reduce amyloid-β production and amyloid-β42-induced IL-1β production. |
| Targets: |
Beta Amyloid | p53 | IL Receptor | Topoisomerase |
| In vitro: |
| J Alzheimers Dis. 2015;43(2):465-77. | | Camptothecin and its analogs reduce amyloid-β production and amyloid-β42-induced IL-1β production.[Pubmed: 25096614] | Compounds derived from natural products are becoming promising alternative drugs/tools in Alzheimer's disease (AD) therapeutics.
METHODS AND RESULTS:
From an in-house natural products library, seventeen hits were selected for their inhibitory effect on the production of amyloid-β (Aβ) with IC50 lower than 10 μM without causing obvious toxicity. Among these compounds, camptothecin (CPT) and its analogs showed inhibitory effects on amyloid-β 1-42 (Aβ42) with the IC50 value in the nanomolar range in HEKsw cells and SHSY5Ysw cells. Further studies showed that CPT and its analogs inhibited Aβ42 via a p53 dependent pathway. Meanwhile, CPT and its analogs could also inhibit Aβ42 induced IL-1β production in the THP-1 cells.
CONCLUSIONS:
Taken together, our results indicate that CPT and its analogs would be a promising therapeutic candidates for AD. |
|
| In vivo: |
| J Drug Target. 2014 Dec;22(10):913-26. | | Development and evaluation of magnetic microemulsion: tool for targeted delivery of camptothecin to BALB/c mice-bearing breast cancer.[Pubmed: 25119147] | Development and evaluation of camptothecin-loaded-microemulsion (ME) and -magnetic microemulsion (MME) for passive/active-targeted delivery to BALB/c mice-bearing breast cancer.
METHODS AND RESULTS:
Based on the pseudo-ternary phase diagrams camptothecin-loaded-MEs and -MMEs were developed using benzyl alcohol:Captex 300 (3:1), TPGS:Tween 80 (2:1) and water. Furthermore, characterized for their droplet size distribution, magnetic susceptibility and effect of droplet size in plasma and evaluated for in vitro and in vivo targeting potential, drug release, haemolytic potential, cytotoxicity, genotoxicity, in vivo biodistribution and lactone ring stability.
Drug-loaded MEs showed uniform droplet distribution, extended drug release (76.07 ± 4.30% at 24 h), acceptable level of haemolytic activity (<20%), significant cytotoxicity (129 ± 3.9 ng/mL) against MCF-7 cancer cells and low DNA damage in lymphocytes. Targeting potential of MMEs was documented in 4T1 breast cancer-induced BALB/c mice. MMEs were concentrated more at the target tissue on introduction of external magnetic field. In vivo biodistribution study documented the active targeting of 5067.56 ± 354.72 ng/gm and passive targeting of 1677.58 ± 134.20 ng/gm camptothecin to breast cancer from MME and ME, respectively. Lactone stability study shows around 80% of the lactone stable at 24 h.
CONCLUSIONS:
Developed ME and MME may act as a promising nanocarrier for efficient targeting of breast cancer tissues. |
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