Synthesis of nucleosidyl rifamycins as inhibitors of human immunodeficiency virus type 1

C. Bartolucci, L. Cellai, L. Mannina, M. Marzano, M. Brufani, L. Filocamo, S. Messina, V. Brizzi, A. Benedetto, A. Di Caro

Research output: Contribution to journalArticlepeer-review


In the search for potential nucleoside/non-nucleoside mixed type inhibitors of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase, we synthesized a new set of rifamycin S derivatives, containing AZT connected via its hydroxyl at 5' C, through o spacer, to the third C of rifamycin S. The length of the spacer was eight, nine or 14 atoms. Rifamycin S was also used in its 21,23-O,O-isopropylidene derivative form, and in one case thymidine replaced AZT. These nucleosidyl rifamycins were weak inhibitors of isolated HIV-1 reverse transcriptase. The inhibitory power was weak most probably because their large molecular volume hindered the inhibition process, with the exception of the thymidine derivative, the AZT derivatives, at concentrations in the range 0.04-0.07 μM, proved non-toxic and inhibited the replication of HIV-1 in C8166 T lymphocytes. This activity appears to be owing to AZT released by the derivatives upon hydrolysis in solution. The present compounds require further development as mixed type reverse transcriptase inhibitors and can be considered non-toxic lipophilic prodrugs of AZT.

Original languageEnglish
Pages (from-to)215-221
Number of pages7
JournalAntiviral Chemistry and Chemotherapy
Issue number3
Publication statusPublished - May 1997


  • AZT prodrugs
  • HIV
  • non-nucleoside reverse transcriptase inhibitors
  • rifamycins

ASJC Scopus subject areas

  • Virology
  • Pharmacology

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