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Antimicrobial Agents and Chemotherapy, August 2006, p. 2857-2859, Vol. 50, No. 8
0066-4804/06/$08.00+0     doi:10.1128/AAC.01223-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Alkoxyalkyl Esters of (S)-9-[3-Hydroxy-2-(Phosphonomethoxy)Propyl]Adenine Are Potent Inhibitors of the Replication of Wild-Type and Drug-Resistant Human Immunodeficiency Virus Type 1 In Vitro

Karl Y. Hostetler,* Kathy A. Aldern, William B. Wan, Stephanie L. Ciesla, and James R. Beadle

Department of Medicine, Division of Infectious Disease, University of California, San Diego, and Veterans Medical Research Foundation, La Jolla, California

Received 19 September 2005/ Returned for modification 9 November 2005/ Accepted 8 May 2006

(S)-9-[3-Hydroxy-2-(phosphonomethoxy)propyl]adenine [(S)-HPMPA], is an effective broad-spectrum antiviral against many DNA viruses but has been reported to be inactive against human immunodeficiency virus (HIV). We synthesized several alkoxyalkyl esters of (S)-HPMPA and now report that hexadecyloxypropyl-(S)-HPMPA [HDP-(S)-HPMPA] and octadecyloxyethyl-(S)-HPMPA [ODE-(S)-HPMPA]had 50% effective concentrations of 0.4 to 7.0 nanomolar and were nearly fully active against HIV variants having reverse transcriptase mutations M184V and K103N and against a zidovudine-resistant variant with mutations D67N, K70R, T215Y, and K219Q. Resistance to HDP-(S)-HPMPA and ODE-(S)-HPMPA was noted for a mutant with mutation K65R. HDP-(S)-HPMPA is also active against herpes simplex virus type 1, human cytomegalovirus, hepatitis B virus, adenoviruses, and orthopoxviruses and is worthy of further evaluation as a possibly therapy for HIV infection.

* Corresponding author. Mailing address: Division of Infectious Disease, Department of Medicine, University of California, San Diego, Mail Code 0676, 9500 Gilman Drive, La Jolla, CA 92093-0676. Phone: (858) 552-8585, ext. 2616. Fax: (858) 534-6133. E-mail: khostetl{at}ucsd.edu.

Antimicrobial Agents and Chemotherapy, August 2006, p. 2857-2859, Vol. 50, No. 8
0066-4804/06/$08.00+0     doi:10.1128/AAC.01223-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Morrey, J. D., Korba, B. E., Beadle, J. R., Wyles, D. L., Hostetler, K. Y. (2009). Alkoxyalkyl Esters of 9-(S)-(3-Hydroxy-2-Phosphonomethoxypropyl) Adenine Are Potent and Selective Inhibitors of Hepatitis B Virus (HBV) Replication In Vitro and in HBV Transgenic Mice In Vivo. Antimicrob. Agents Chemother. 53: 2865-2870 [Abstract] [Full Text]  
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