Sheldon D. Weed

Antiviral and Interferon-Inducing Properties of 1,5-Diamino Anthraquinones

A series of anthraquinones with amino substituents at the 1,5 positions were found to induce interferon in mice. A prototype compound, 1,5-bis[(3-morpholinopropyl)amino]-anthraquinone (Ia), was an effective antiviral agent when administered either orally or parenterally. Peak interferon titers were found 12 to 24 h after drug treatment. The minimum oral dose of Ia required to induce serum interferon or to protect mice against a lethal virus infection was 62 mg/kg. Mice tolerated an oral dose of at least 30 times this minimum effective dose. A single dose of Ia given up to 6 days prior to infection had significant protective activity. Biological properties of Ia were compared with those of three other 1,5-diamino anthraquinones, which also induced interferon and demonstrated antiviral activity in mice. The most active compound was 1,5-bis[[2-(diethylamino)ethyl]amino]-anthraquinone (Ib), which protected mice against virus infection at a dose as low as 8 mg/kg (less than 1/60 its maximum tolerated dose). Mice developed hyporeactivity to interferon induction if the same inducer was injected daily, although by alternating between different inducers the loss of interferon responsiveness could be avoided.

Didemnins A and B. Effectiveness against cutaneous herpes simplex virus in mice

The antiviral activity of didemnin A and didemnin B against a lethal Semliki Forest virus (SFV) infection of mice and a cutaneous herpes type 1 infection in hairless mice was evaluated. Both compounds significantly decreased the severity of herpesvirus lesions if topical treatment with either didemnin A or didemnin B was started 2 days prior to infection. The survival rate was significantly greater (P = 0.03) in the didemnin B treated group than in controls. If initiation of treatment was delayed until 1 h after infection, no activity was obtained. The compounds were not active against cutaneous herpesvirus infection when injected intraperitoneally (i.p.). Didemnin B at concentrations as low as 1.5 micrograms, administered topically 3 times daily for 5 days, produced skin irritation. Eight times this level of didemnin A could be administered before similar toxicity was observed. The limited activity of didemnins A and B coupled with irritation at the treatment site limits their usefulness in treating cutaneous herpesvirus infection. Neither didemnin A nor B had significant activity in SFV-infected mice.

Glyoxal and related compounds as potential blood sterilizing agents.

Summary Both glyoxal and β-ethoxy-α-ketobutyraldehyde (Kethoxal) were more potent virucidal agents than β-propiolactone (BPL). Glyoxal was less lytic for human erythrocytes than was Kethoxal or BPL. None of the chemicals showed significant toxicity for plasma proteins as measured by electrophoresis. These experiments indicate that glyoxal may be of potential value in the sterilization of human blood and plasma.

Efficacy of 5,6-Dihydro-5-Azathymidine Against Cutaneous Herpes Simplex Virus in Hairless Mice

5,6-Dihydro-5-azathymidine, administered subcutaneously, was active both prophylactically and therapeutically against cutaneous herpesvirus infection of hairless mice. Activity was comparable to that obtained with adenine arabinoside.

Efficacy of N6- (2-Hydroxyethyl) Adenine against Coe Virus Infection in Mice.

Summary The compound N6-(2-hydroxy-ethyl)adenine (HEA) was effective in favorably modifying experimental Coe virus infection in mice. HEA showed antiviral activity when a single injection, approximately one-tenth the lethal dose, was given from 24 hours before to 17 hours after virus inoculation. The toxicity, but not the antiviral activity of HEA, was partly reversed by simultaneous treatment with a xanthine oxidase inhibitor.