Anti-HIV natural product (+)-calanolide A is active against both drug-susceptible and drug-resistant strains of Mycobacterium tuberculosis

Bioorg Med Chem. 2004 Mar 1;12(5):1199-207. doi: 10.1016/j.bmc.2003.11.012.


Naturally occurring anti-HIV-1 agent (+)-calanolide A was found to be active against all of the strains of Mycobacterium tuberculosis tested, including those resistant to the standard antitubercular drugs. Efficacy evaluations in macrophages revealed that (+)-calanolide A significantly inhibited intracellular replication of M. tuberculosis H37Rv at concentrations below the MIC observed in vitro. Preliminary mechanistic studies indicated that (+)-calanolide A rapidly inhibits RNA and DNA synthesis followed by an inhibition of protein synthesis. Compared with known inhibitors, this scenario is more similar to effects observed with rifampin, an inhibitor of RNA synthesis. Since (+)-calanolide A was active against a rifampin-resistant strain, it is believed that these two agents may involve different targets. (+)-Calanolide A and its related pyranocoumarins are the first class of compounds identified to possess antimycobacterial and antiretroviral activities, representing a new pharmacophore for anti-TB activity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Anti-HIV Agents / pharmacology*
  • Antineoplastic Combined Chemotherapy Protocols
  • Antitubercular Agents / pharmacology*
  • Cell Line
  • Chlorocebus aethiops
  • Cisplatin
  • Coumarins / pharmacology*
  • DNA / biosynthesis
  • Drug Resistance, Bacterial
  • Ifosfamide
  • Inhibitory Concentration 50
  • Macrophages / microbiology
  • Microbial Sensitivity Tests
  • Mitomycin
  • Mycobacterium tuberculosis / drug effects*
  • Pyranocoumarins / chemistry
  • Pyranocoumarins / pharmacology
  • RNA / biosynthesis
  • Rifampin
  • Vero Cells
  • Virus Replication / drug effects


  • Anti-HIV Agents
  • Antitubercular Agents
  • Coumarins
  • Pyranocoumarins
  • Mitomycin
  • RNA
  • DNA
  • Cisplatin
  • calanolide A
  • Ifosfamide
  • Rifampin

Supplementary concepts

  • MIP protocol