alkylphosphocholine

Alkylphosphocholines (APCs) are a class of synthetic ether lipids consisting of a long alkyl chain linked through an ether bond to a phosphocholine head group. This composition gives them amphiphilic properties that enable interactions with membranes and lipid signaling pathways. Miltefosine and edelfosine are among the most studied representatives.

Mechanism and effects: These compounds incorporate into plasma membranes and intracellular membranes, disrupt lipid rafts and phospholipid metabolism, and can cause mitochondrial dysfunction and activation of apoptosis in cancer cells and protozoan parasites. Their selectivity for malignant or infected cells is related to differences in membrane composition, lipid metabolism, and drug uptake.

Applications: Miltefosine is approved for oral treatment of visceral leishmaniasis in several countries and is used off-label for other leishmanial infections; edelfosine has undergone clinical trials as an anticancer agent but is not approved widely. Other APCs have been investigated in preclinical or early clinical studies as anticancer or antiparasitic agents.

Safety and regulatory status: Common adverse effects include gastrointestinal symptoms, hepatotoxicity, and dehydration; miltefosine is teratogenic and contraindicated during pregnancy in many guidelines. Toxicities and pharmacokinetic properties vary among APCs, and long-term safety data are limited.

Research directions: Efforts focus on improving tumor or parasite selectivity, reducing normal tissue toxicity, and exploring combination therapies with conventional anticancer drugs or immunotherapies.