7 Substituted actinomycin D analogs. Chemical and growth inhibitory studies

Article abstract of DOI:10.1021/jm00246a001

The synthesis and biological activity of three 7 substituted actinomycin D derivatives are reported. Three such derivatives, 7 nitro, 7 amino, and 7 hydroxyactinomycin D, were synthesized via new methods which were first tested successfully with a chromophore model system. Of these, 7 nitro and 7 aminoactinomycin D were assayed for growth inhibitory activity against mammalian cells (CCRF CEM human lymphoblastic leukemia) in vitro and against the Ridgway osteogenic sarcoma and the L1210, P1534, and P388 murine leukemias in vivo. In these systems, the inhibitory activity of the 7 substituted analogs was comparable to actinomycin D. In two bacterial systems (L. casei and L. arabinosus) in vitro, on the other hand, these compounds showed inhibitory profiles which were distinctly different from actinomycin D. These studies demonstrate that substitution at the 7 position, which does not interfere with DNA binding, is capable of yielding experimental antitumor agents with significant activity against a variety of tumors.