Relationships between structure and antiretroviral activity of thiosemicarbazone derivatives.

In an attempt to develop anti-AIDS drugs, the compound isatin beta-thiosemicarbazone has been subjected to systematic structural modifications. The resulting synthesized thiosemicarbazone derivatives (TSCDs) were examined for their ability to act as antiretrovirus agents in a model system--2M3/M cell system--consisting of B lymphocytes transformed by the v-abl oncogene and chronically infected with a retrovirus, the Moloney leukemia virus (M-MuLV). The efficacy of the synthesized TSCDs against retroviruses was determined by assaying the therapeutic index (TI) values of the compounds. The results enabled the classification of TSCD groups based on the relationship between chemical structure and antiretroviral activity. The compound N-allylisatin-beta':4'-diallylthiosemicarbazone showed the highest TI value and efficiently suppressed the chronic infection of M-MuLV in continuous long-term treatment.