Castration resistant prostate cancer (CRPC) is known to use fatty acid oxidation (FAO) as one of their main sources of fuel. This suggests that inhibiting FAO could be a favorable route for increased therapeutic effect. We discovered that one of the cisplatin prodrugs which our lab had synthesized showed significant effect at inhibiting fatty acid oxidation, similar to that of carnitine palmitoyltransferase I (CPTI) inhibitor, etomoxir, suggesting that the modifications to cisplatin had an effect at FAO inhibition. That molecule had one axial position with a succinate group and the other position has an aliphatic chain. This discovery led us to synthesize a series of cisplatin prodrugs with aliphatic chains of varying length at the axial positions. A series of 22 different molecules were synthesized with 11 di-subsitituted prodrugs and 11 mono substituted prodrugs, with a succinate moiety on the other axial position in order to investigate whether there was another molecule that can inhibit FAO to a greater extent, while retaining the chemotherapeutic properties of cisplatin and investigate the role of long aliphatic chains on FAO inhibition. <br/>

Series of cisplatin prodrugs to inhibit fatty acid oxidation in prostate cancer

255th National Meeting (2018)

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