MUTAGENIC AND CYTOTOXIC ACTIVITY OF AN ISOCOUMARIN (PAEPALANTINE) ISOLATED FROM PAEPALANTHUS VELLOZIOIDES

A new isocoumarin with antimicrobial activity was isolated from Paepal anthus vellozioides (a native Brazilian plant) and called paepalantine . This study was carried out to assess the mutagenic activity of this new agent in assays with Salmonella typhimurium TA100, TA98, and TA102 and in Chinese hamster ovary (CHO) cell cultures, as well as cytotoxi city to McCoy cells. Paepalantine caused a significant dose-dependent increase in the frequency of revertants in the three strains used in t he assay, both with and without S9 mix, in concentrations varying from 2 to 128 mu g/ plate. The mutagenicity was confirmed in assays with C HO cells treated in the G(1), S, and G(2) phases of the cell cycle. Th ere was an increase in the chromosomal aberration frequency, mainly in the G(2) phase. Furthermore, the mitotic index of the treated culture s (40,80, and 160 mu g/ml) was significantly lower, indicating cytotox icity. The midpoint cytotoxicity values to McCoy cells by the neutral red (NR) and microculture tetrazolium (MTT) techniques resulted in a N R50, and MTT50 of 30 and 38 mu g/ml, respectively. Alterations to the paepalantine structure are suggested to reduce its mutagenic and cytot oxic activity in investigations for its antineoplasic potential (C) 19 97 Wiley-Liss, Inc.