Glucoside Derivatives Of Podophyllotoxin: Synthesis, Physicochemical Properties, And Cytotoxicity
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
Cheng-Ting Zi,1,2,* Liu Yang,2,* Qing-Hua Kong,2 Hong-Mei Li,2 Xing-Zhi Yang,2 Zhong-Tao Ding,3 Zi-Hua Jiang,4 Jiang-Miao Hu,2 Jun Zhou2 1Key Laboratory of Pu-Er Tea Science, Ministry of Education, College of Science, Yunnan Agricultural University, Kunming, 650201, People’s Republic of China; 2State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, People’s Republic of China; 3Key Laboratory of Medicinal Chemistry for Nature Resource, Ministry of Education, School of Chemical Science and Technology, Yunnan University, Kunming 650091, People’s Republic of China; 4Department of Chemistry, Lakehead University, Thunder Bay ON P7B 5E1, Canada*These authors contributed equally to this workCorrespondence: Zi-Hua JiangDepartment of Chemistry, Lakehead University, 955 Oliver Road, Thunder Bay ON P7B 5EI, CanadaTel +1 807 766 7171Fax +1 807 346 7775Email zjiang@lakeheadu.caJiang-Miao HuState Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, No. 132, Lanhei Road, Kunming 650201, People’s Republic of ChinaTel +86 871 6522 3264Fax +86 871 6522 3261Email hujiangmiao@mail.kib.ac.cnBackground: Widespread concern of the side effects and the broad-spectrum anticancer property of podophyllotoxin as an antitumor agent highlight the need for the development of new podophyllotoxin derivatives. Although some per-butyrylated glucosides of podophyllotoxin and 4β-triazolyl-podophyllotoxin glycosides show good anticancer activity, the per-acetylated/free of podophyllotoxin glucosides and their per-acetylated are not well studied.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.Keywords: podophyllotoxin, glucoside, synthesis, cytotoxicity, physicochemical properties
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it