Abstract | BACKGROUND: METHODS: A few glucoside derivatives of PPT were synthesized and evaluated for their in vitro cytotoxic activities against five human cancer cell lines, HL-60 ( leukemia), SMMC-7721 ( hepatoma), A-549 ( lung cancer), MCF-7 ( breast cancer), and SW480 ( colon cancer), as well as the normal human pulmonary epithelial cell line (BEAS-2B). In addition, we investigated the structure-activity relationship and the physicochemical property-anticancer activity relationship of these compounds. RESULTS: Compound 6b shows the highest cytotoxic potency against all five cancer cell lines tested, with IC50 values ranging from 3.27±0.21 to 11.37±0.52 μM. We have also found that 6b displays higher selectivity than the etoposide except in the case of HL-60 cell line. The active compounds possess similar physicochemical properties: MSA > 900, %PSA < 20, ClogP > 2, MW > 700 Da, and RB > 10. CONCLUSION: We synthesized several glucoside derivatives of PPT and tested their cytotoxicity. Among them, compound 6b showed the highest cytotoxicity. Further studies including selectivity of active compounds have shown that the selectivity indexes of 6b are much greater than the etoposide except in the case of HL-60 cell line. The active compounds possessed similar physicochemical properties. This study indicates that active glucoside analogs of podophyllotoxin have potential as lead compounds for developing novel anticancer agents.
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Authors | Cheng-Ting Zi, Liu Yang, Qing-Hua Kong, Hong-Mei Li, Xing-Zhi Yang, Zhong-Tao Ding, Zi-Hua Jiang, Jiang-Miao Hu, Jun Zhou |
Journal | Drug design, development and therapy
(Drug Des Devel Ther)
Vol. 13
Pg. 3683-3692
( 2019)
ISSN: 1177-8881 [Electronic] New Zealand |
PMID | 31695335
(Publication Type: Journal Article)
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Copyright | © 2019 Zi et al. |
Chemical References |
- Antineoplastic Agents, Phytogenic
- Glucosides
- Podophyllotoxin
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Topics |
- Antineoplastic Agents, Phytogenic
(administration & dosage, chemistry, pharmacology)
- Cell Line, Tumor
- Glucosides
(chemistry)
- Humans
- Inhibitory Concentration 50
- Neoplasms
(drug therapy, pathology)
- Podophyllotoxin
(administration & dosage, chemistry, pharmacology)
- Structure-Activity Relationship
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