Synthesis and anticancer evaluation of spermatinamine analogues

Basem A Moosa; Sunil Sagar; Song Li; Luke Esau; Mandeep Kaur; Niveen M Khashab

doi:10.1016/j.bmcl.2016.01.083

Synthesis and anticancer evaluation of spermatinamine analogues

Bioorg Med Chem Lett. 2016 Mar 15;26(6):1629-1632. doi: 10.1016/j.bmcl.2016.01.083. Epub 2016 Feb 4.

Authors

Basem A Moosa¹, Sunil Sagar², Song Li³, Luke Esau², Mandeep Kaur⁴, Niveen M Khashab³

Affiliations

¹ Controlled Release and Delivery (CRD) Lab, Chemical Life Sciences and Engineering, King Abdullah University of Science and Technology, Thuwal 23955-6900, Saudi Arabia; Center for Advanced Membranes and Porous Materials, King Abdullah University of Science and Technology, Thuwal 23955-6900, Saudi Arabia. Electronic address: [email protected].
² Biomolecular Lab, Computational Bioscience Research Center, King Abdullah University of Science and Technology, Thuwal 23955-6900, Saudi Arabia.
³ Controlled Release and Delivery (CRD) Lab, Chemical Life Sciences and Engineering, King Abdullah University of Science and Technology, Thuwal 23955-6900, Saudi Arabia; Center for Advanced Membranes and Porous Materials, King Abdullah University of Science and Technology, Thuwal 23955-6900, Saudi Arabia.
⁴ Biomolecular Lab, Computational Bioscience Research Center, King Abdullah University of Science and Technology, Thuwal 23955-6900, Saudi Arabia; School of Molecular and Cell Biology, University of the Witwatersrand, Private Bag 3, Wits, 2050, Johannesburg, South Africa.

PMID: 26874403
DOI: 10.1016/j.bmcl.2016.01.083

Abstract

Spermatinamine was isolated from an Australian marine sponge, Pseudoceratina sp. as an inhibitor of isoprenylcysteine carboxyl methyltransferase (Icmt), an attractive and novel anticancer target. Herein, we report the synthesis of spermatinamine analogues and their cytotoxic evaluation against three human cancer cell lines, that is, cervix adenocarcinoma (HeLa), breast adenocarcinoma (MCF-7), and prostate carcinoma (DU145). Analogues 12, 14 and 15 were found to be the most potent against one or more cell lines with the IC50 values in the range of 5-10 μM. The obtained results suggested that longer polyamine linker along with aromatic oxime substitution provided the most potent analogue compounds against cancer cell lines.

Keywords: Bromotyrosine; Cancer; Cytotoxicity; Natural products; Spermatinamine.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / chemical synthesis*
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Cell Line, Tumor
Cell Proliferation / drug effects
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Humans
Molecular Structure
Spermine / analogs & derivatives*
Spermine / chemical synthesis
Spermine / chemistry
Spermine / pharmacology
Structure-Activity Relationship
Tyrosine / analogs & derivatives*
Tyrosine / chemical synthesis
Tyrosine / chemistry
Tyrosine / pharmacology

Substances

Antineoplastic Agents
spermatinamine
Spermine
Tyrosine