kahalalide-f and discodermolide

Natural compounds derived from marine organisms have shown a wide variety of anti-tumor effects and a lot of attention has been drawn to further development of the isolated compounds. A vast quantity of individual chemical structures from different organisms has shown a variety of apoptosis inducing mechanisms in a variety of tumor cells. The bis-steroidal cephalostatin 1 for example, induces apoptosis via activation of caspases whereas the polyketide discodermolide inhibits cell growth by binding to and stabilizing microtubule and salisporamide A, the product of an actinobacterial strain, is an inhibitor of the proteasome. This great variety of mechanisms of action can help to overcome the multitude of resistances exhibited by different tumor specimens. Products from marine organisms and their synthetic derivates are therefore an important source for new therapeutics for single agent or combined therapy with other chemotherapeutics to support the struggle against cancer.

Topics: Alkaloids; Alkanes; Animals; Anti-Bacterial Agents; Antineoplastic Agents; Apoptosis; Aquatic Organisms; Biological Products; Bryostatins; Carbamates; Cell Proliferation; Depsipeptides; Dioxoles; Drug Screening Assays, Antitumor; Humans; Lactones; Macrolides; Microtubules; Models, Chemical; Neoplasms; Phenanthrolines; Phenazines; Proteasome Endopeptidase Complex; Pyrones; Pyrroles; Quinolines; Spiro Compounds; Steroids; Tetrahydroisoquinolines; Thiazoles; Trabectedin

The natural products kahalalide F, halichondrin B, and discodermolide are relatively large structures that were originally harvested from marine organisms. They are oxygen rich structures that, to varying degrees, should have the ability to bind iron (II or III) by Fe-O and/or Fe-N bonds. In this semi empirical study, the binding of these natural products to iron (II) is studied and the aqueous stability factor (ASF) is used to determine which bonding configuration is most stable. The energy, the complex charge (+1), the average Fe-O (or Fe-N) bond distances and the dipole moments are used to calculate the ASF. The ASF provides insight to which complex will be the most stable and water soluble, important for a medicinal application. The ability of a molecule with a more than six oxygen and/or nitrogen atoms to bind iron (hexavalent, octahedral) by shifting which six atoms (O/N) are bound to the iron qualifies it as a polarity adaptive molecule.

Topics: Alkanes; Animals; Antineoplastic Agents; Biological Products; Carbamates; Cell Line, Tumor; Chemical Phenomena; Computational Biology; Depsipeptides; Ethers, Cyclic; Humans; Inhibitory Concentration 50; Iron; Lactones; Macrolides; Models, Molecular; Molecular Conformation; Neoplasms; Oxygen; Pyrones; Siderophores; Structure-Activity Relationship