T-Lymphocyte depletion induced in rats by analogs of tilorone hydrochloride

Abstract

Tilorone, a bis-basic substituted fluorene-9-one compound, and four of its analogs depleted lymphocytes in thymic-dependent areas in both the spleen and lymph nodes after both sc and oral administration to rats. Twenty-nine out of 39 analogs administered by either route depleted lymphocytes in the spleen, lymph nodes, or in both. Active analogs encompassed a wide variety of polycylic ring structures including fluorene, fluoranthene, anthraquinone, dibenzothiophene, dibenzofuran, and even a bicyclic ring (naphthyridine) and a simple pyridine ring. The two teriary amine side chains in active compounds included ether, ketone, ester, alkane, and thioether but not carboxamide, thioester, or sulfonamide linkages. The mesenteric lymph node was especially susceptible to analogs administered by the oral route. The subcutaneous route was often associated with acute necrosis of cells in the thymic cortex, probably an indirect effect of stress and adrenal stimulation, which had the consequence of blocking lymphocyte depletion in the spleen and nodes. This complicating effect of certain compounds may be partly responsible for the inability to correlate lymphocyte-depletion with antiviral activity.