Optimizing Arsenic Therapy by Selectively Targeting Leukemia Cells.

Arsenic, in the simple form of arsenic trioxide, is currently marketed for the treatment of acute promyelocytic leukemia. Due to the multifaceted mechanisms of action of arsenic, it has also shown promise in other types of leukemias but is hindered by its toxic effects toward normal cells. This research has aimed to determine whether tumor-homing peptide complexes of arsenic can be designed and developed to strategically target specific cancers. The end goal is to achieve dose reduction and decreased side effects of the resultant arsenic therapeutic agent. In this article, we present the synthesis, characterization, and stability studies of a new class of As-peptide complexes designed to target leukemia. In vitro biological studies of the most stable complex show 1000 times greater toxicity toward leukemia cells over human blood cells, indicating potential for progression to in vivo studies.

Alkaloids from the root of Indonesian Annona muricata L.

Annona muricata L. has been used traditionally in Indonesia to treat disease. Phytochemical studies on the alkaloid fractions from the root of Annona muricata L. from Malang-Indonesia resulted in the isolation of an unreported benzylisoquinoline alkaloid (+)-xylopine 5 as well as four known alkaloids (1-4). The crude methanol extract and alkaloid fractions were tested against Plasmodium falciparum K1 and against bacteria (Escherichia coli, Klebsiella pneumonia, Acinetobacter buamanii, Pseudomonas aeruginosa, Methicillin-resistant Staphylococcus aureus) with insignificant activities (MIC > 32 µg/mL). Individual alkaloids were tested against a human suspension cancer cell line (HL-60 leukemia cells) and two human fibroblastic cancer cell lines (A549 lung cancer cells and HepG2 liver cancer cells) in which compound 5 was the most toxic alkaloid with IC50 values ranging from 20 to 80 µM.

Anti-cancer Evaluation of Depsides Isolated from Indonesian Folious Lichens: Physcia millegrana, Parmelia dilatata and Parmelia aurulenta.

Cancer is a serious health burden on global societies. The discovery and development of new anti-cancer therapies remains a challenging objective. Although it has been shown that lichen secondary metabolites may be potent sources for new anti-cancer agents, the Indonesian- grown folious lichens, Physcia millegrana,Parmelia dilatata and Parmeila aurulenta, have not yet been explored. In this study exhaustive preparative high-performance liquid chromatography was employed to isolate the lichen constituents with spectroscopic and spectrometric protocols identifying nine depsides 9-17, including the new methyl 4-formyl-2,3-dihydroxy-6-methylbenzoate 13. The cytotoxicity of the depsides towards cancer cells was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The results indicated lowest toxicity of the depsides towards human A549 lung cancer cells. Importantly, the di-depsides (11, 12 and 17) showed greatest toxicity, indicating that these structures are biologically more active than the mono-depsides against the HepG2 liver cancer, A549 lung cancer and HL-60 leukemia cell lines.