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Introduction of Z-GP scaffold into procarbazine reduces spermatoxicity and myelosuppression.
- Source :
-
Bioorganic Chemistry . Mar2019, Vol. 83, p461-467. 7p. - Publication Year :
- 2019
-
Abstract
- Graphical abstract Highlights • Z-GP-Pcb has been designed and synthesized with an overall yield of 32.7%. • Z-GP-Pcb targets to FAPα. • Z-GP-Pcb shows less spermatoxicity than Pcb. • Z-GP-Pcb demonstrates less myelosuppression than Pcb. Abstract Incorporation of carbobenzoxy-glycylprolyl (Z-GP) to either α or β position of the hydrazine moiety in procarbazine (Pcb) has been carried on in 5-steps process. The overall yield was 32.7%. The new entity Z-GP-Pcb was confirmed targeting to fibroblast activation protein-α (FAPα). Z-GP-Pcb may be hydrolyzed by either isolated rhFAPα or tumor homogenate. It was shown far less cytotoxicity against NCI-H460 cell line than Pcb. Z-GP-Pcb was displayed the potency to reduce spermatoxcity in H22-bearing mice. The mechanism may be ascribed to the blockade of dehydrogenation by α-glycerolphosphate dehydrogenase. This candidate was further proved equal antitumor activity to Pcb. However, the introduction of Z-GP scaffold decreased myelosuppression. All the evidences support that Z-GP-Pcb is a better antitumor agent than Pcb. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00452068
- Volume :
- 83
- Database :
- Academic Search Index
- Journal :
- Bioorganic Chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 134739862
- Full Text :
- https://doi.org/10.1016/j.bioorg.2018.11.011