nifurtimox

Nifurtimox (BAY-A-2502) is an antiprotozoal agent (IC50s = 9.91, 12.28, and 10.44 μM against Taluahuén, LQ, and Brener strains of T. cruzi- epimastigotes, respectively).

12-methyl Myristic acid methyl ester is a methylated fatty acid methyl ester that has been found in vermicomposts of cattle manure, carica papaya leaves, and cuticular wax of K. africana. It is a volatile compound in lipid-lowering granulated tea. Levels of 12-methyl myristic acid methyl ester are decreased in T. cruzi treated with nifurtimox compared to non-treated controls.

Antitrypanosomal agent 6 (compound 18a) is a potent antitrypanosomal agent demonstrating good ADME properties, with an IC50 of 0.47 μM against Trypanosoma brucei (T. brucei), making it more than twice as active as Nifurtimox; it also exhibits a strong interaction with and selective binding to AT-rich DNA.

The Antitrypanosomal agent 7 (compound 18c) is a potent anti-trypanosome agent and shows good ADME properties. The Antitrypanosomal agent 7 was more than two-fold more active against T. brucei (IC50: 0.71 μM) than Nifurtimox. Antitrypanosomal agent 7 has a strong interaction with DNA and can selectively bind to AT-rich DNA.

RKS262 is a specific cyclin/CDK inhibitor. RKS262 was identified by structural optimization of Nifurtimox which is currently undergoing phase II clinical trials to treat high-risk neuroblastoma. In a NCI(60) cell-line assay RKS262 exhibited significant cytotoxicity in ovarian cancer cells and a variety of other cell lines exceeding effects of commercial drugs such as cisplatin, 5-FU, cyclophosphamide or sapacitabine. Various leukemia cell-lines were most sensitive (GI(50): ~ 10 nM) while several non-small cell lung cancer cell lines and few cell lines from other tissues were relatively resistant (GI(50) > 1 µM) to RKS262 treatment.