Calixarenes with host-mediated potency in experimental tuberculosis: Further evidence that macrophage lipids are involved in their mechanism of action

Abstract

Some time ago, it was found that attachment of hydrophilic polyoxyethylene chains to various hydrophobic phenols and alcohols gave water-soluble products which, although inactive in vitro, influenced an experimental tuberculous infection. With short chains the infection was suppressed, and with long chains it was promoted. Later work concentrated on Macrocyclon (short chain) and HOC-60 (long chain), both derived from a hydrophobic, polyphenolic calixarene. Growth of Mycobacterium tuberculosis inside macrophages (Mφ) was inhibited by Macrocyclon and stimulated by HOC-60. Also, triglyceride lipase from Mφ extracts and an extracellular phospholipase were inhibited by Macrocyclon and stimulated by HOC-60. This suggestion of a mechanism has been strengthened by the finding that Mφ cultivated in monolayers and treated with Macrocyclon showed accumulation of lipid and little formation of fatty acid after incubation of killed cells. With HOC-60, lipid was depleted and much fatty acid was found.