mutated T139I reverse transcriptase is resistant to Calanolide A action. Therapeutic potential Calanolide A is active against HIV-1 virus but ineffective against HIV-2. It is also active against resistant strains of HIV such as eAZT-resistant G-9106 strain of HIV-1 and pyridinone-resistant A17 strain. It is also active against NNRTI-related mutations of K103N and Y181C. Calanolide A, Costatolide, and dihydrocostatolide can be used together with azidothymidine (AZT), indinavir, nelfinavir, and saquinavir for enhanced activity against the HIV-1 virus. Although initially, Calanolide A did not show any activity against cancer cell lines in the 1980s, later experimentation in 2003 showed antiproliferative and antitumor-promoting property through inhibition of TPA-induced EBV-EA activation in Raji cell lines. TPA (12-O-Tetradecanoylphorbol-13-acetate) is a tumour promoter used in biomedical research. EBV-EA is Epstein–Barr virus early antigen. In 2003, the Calanolide A compound was found to have anti-tuberculosis activity. It is active against both drug-susceptible and drug resistant strains of mycobacteria such as H37Ra and H37Rv strains. The antitubercular activities of Calanolide A is comparable to isoniazid and is active against rifampicin and streptomycin resistant M. tuberculosis strains. Side effects Calanolide A has a relatively good safety profile. A Phase I clinical trial done in 2001 on 47 healthy subjects showed that the side effects were taste alteration, headache, belching, and nausea. References Antiretroviral drugs Lactones Secondary alcohols Enones Heterocyclic compounds with 4 rings