Paper Title
Manumycin a is a Promising Natural Compound for Pharmacology and Medicine due to the Lack of Genotoxicity

Manumycin A is a natural antibiotic isolated from Streptomyces parvus. It exhibits various biological activities and is known as a Ras farnesyltransferase inhibitor. Despite of extensive research confirming several medicinal properties, its genotoxicity has not been investigated so far. The present study was designed to test potential genotoxic effect of manumycin A at two levels: primary/promutagenic DNA lesions and gene mutations. Primary genetic changes were detected using the comet assay and gene mutations using the Ames/Salmonella typhimurium assay. The potential genotoxic effect of the combined treatment of manumycin A and phloroglucinol – hyperforin (isolated from Hypericum perforatum L.) was also assayed by the Ames assay. The results showed that manumycin A did not significantly increase the primary DNA damages (mainly single-strand DNA breaks) in the comet assay and the number of his+ revertants (in comparison to the negative control) in the Ames test. Moreover, our findings from the combined application of manumycin A and hyperforin on bacterial strains proved that both natural compounds were not genotoxic. DNA-topology assay revealed that manumycin A did not induce DNA damage. These findings indicate that manumycin A, applied as a single agent or in combination with another natural compound, is a promising natural compound for pharmacology and medicine. Keywords - Manumycin A, Genotoxicity, Primary DNA Damage, Gene Mutations, Hyperforin, Comet Assay, Ames Assay, DNA-Protectivity