Bioorg Med Chem Lett. 2016 Mar 15;26(6):1629-32.
Synthesis and anticancer evaluation of spermatinamine analogues
Basem A. Moosa a,b, Sunil Sagar c, Song Li a,b, Luke Esau c, Mandeep Kaur c,d, Niveen M. Khashab a,b
a Controlled Release and Delivery (CRD) Lab, Chemical Life Sciences and Engineering, King Abdullah University of Science and Technology, Thuwal 23955-6900, Saudi Arabia
b Center for Advanced Membranes and Porous Materials, King Abdullah University of Science and Technology, Thuwal 23955-6900, Saudi Arabia
c Biomolecular Lab, Computational Bioscience Research Center, King Abdullah University of Science and Technology, Thuwal 23955-6900, Saudi Arabia
d School of Molecular and Cell Biology, University of the Witwatersrand, Private Bag 3, Wits, 2050, Johannesburg, South Africa
Natural products derived from marine sponges such as spermatinamine analogues have gained a lot of attention due to their unique biochemistry. Herein, a library of spermatinamine analogues has been designed and synthesized. The lead compounds were screened for their in vitro activity on cervix adenocarcinoma (HeLa), breast adenocarcinoma (MCF-7), and prostate carcinoma (DU145) cell lines at different time intervals. Among the twelve novel compounds, 5 compounds were found to be potent in terms of IC50 in mM range. The obtained results suggest that longer polyamine linkers together with hydrophobic oxime substitution provided the most potent and selective compounds < 10 mM against cancer cell lines.
KEYWORDS: Bromotyrosine; Cancer; Cytotoxicity; Natural products; Spermatinamine
Fig 1: Spermatinamine analogues showing different type of polyamine linkers and oxime substituents.
Fig 2: Percentage of growth inhibition for MCF-7 cancer cells after treatment with five Spermatinamine analogues at different concentration (0, 1.25, 2.5, 5, 10, 25, 50, 100 mM) respectively for 24 h.
Table 1: Cytotoxicity (IC50 in mM) of most potent analogues against cancer cell lines (HeLa, MCF-7 and DU145)
We gratefully acknowledge King Abdullah University of Science and Technology (KAUST) – KSA and SEDCO grant for the financial support.