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Design, Synthesis, and Cytotoxicity Evaluation of Novel Griseofulvin Analogues with Improved Water Solubility.

Design, Synthesis, and Cytotoxicity Evaluation of Novel Griseofulvin Analogues with Improved Water Solubility.

Authors :
Hamdy AK
Sheha MM
Abdel-Hafez AA
Shouman SA
Source :
International journal of medicinal chemistry [Int J Med Chem] 2017; Vol. 2017, pp. 7386125. Date of Electronic Publication: 2017 Dec 07.
Publication Year :
2017

Abstract

Griseofulvin 1 is an important antifungal agent that has recently received attention due to its antiproliferative activity in mammalian cancer cells. Study of SAR of some griseofulvin analogues has led to the identification of 2'-benzyloxy griseofulvin 3 , a more potent analogue which retards tumor growth through inhibition of centrosomal clustering. However, similar to griseofulvin 1 , compound 3 exhibited poor aqueous solubility. In order to improve the poor water solubility, six new griseofulvin analogues 5 - 10 were synthesized and tested for their antiproliferative activity and water solubility. The semicarbazone 9 and aminoguanidine 10 analogues were the most potent against HCT116 and MCF-7 cell lines. In combination studies, compound 9 was found to exert synergistic effects with tamoxifen and 5-fluorouracil against MCF-7 and HCT116 cells proliferation, respectively. The flow cytometric analysis of effect of 9 on cell cycle progression revealed G2/M arrest in HCT116. In addition, compound 9 induced apoptosis in MCF-7 cells. Finally, all synthesized analogues revealed higher water solubility than griseofulvin 1 and benzyloxy analogue 3 in pH 1.2 and 6.8 buffer solutions.

Details

Language :
English
ISSN :
2090-2069
Volume :
2017
Database :
MEDLINE
Journal :
International journal of medicinal chemistry
Publication Type :
Academic Journal
Accession number :
29362676
Full Text :
https://doi.org/10.1155/2017/7386125