Antitumor Activity of the Cyclo (L-Phenyl, L-Prolyl) Diketopiperazines Produced By a Newly Isolated Streptomyces Sp. A4.4

This paper describes the identification of antitumor Cyclo (L-phenyl, L-prolyl) Diketopiperazines in a newly isolated Streptomyces sp. Strptomyces sp strain A 4.4 was isolated from soil samples collected from Sudan, purified and screened for their antimicrobial activity against pathogenic microbes, and taxonomically characterized on the basis of morphological and physiological characteristics, phylogenetic analysis and genotypic data. Cultural characteristic studies strongly suggested that these strains are members of the genus Streptomyces. The comparison of the 16S rRNA sequence of the A 4.4 isolate with those sequences submitted to GenBank demonstrated that this strain was 94% similar to the 16S rRNA sequence to number of isolates all of which were Streptomyces species, However, there are many differences between strain A 4.4 and those strains according to the published data. The phylogenetic tree, suggested that Streptomyces sp A 4.4 arose from different node which suggested that this organism was not a closely related species. A 4.4 was proposed as a novel Streptomyces species. The pure active antibiotics were isolated from the culture supernatant and from the biomass using reverse phase HPLC-DAD. Spectroscopical analysis employing Mass, 1H and 13C NMR spectra data the compound was chemically characterized as Cyclo-(Proline--Phenylalnine). cyclo (pro-phe), produced by these identified Streptomyces strains showed significant anticancer effect against human cervical carcinoma cells and Glioma UG-87 cells using MTT assay. The two antibiotics at different concentrations (1µg ml-1, 10µg ml-1, 20µg, 30µg ml-1 and 40µg ml-1) of the compounds for 48 hour incubation. caused death of 90% of cancer cells in comparison to the control cells. In conclusion, we have isolated and identified a new cyclo (phenylalanine-proline) producing streptomyces from Sudanese soil and characterized as Streptomyces A4.4 by 16S rRNA homology. This Streptomyces sp. A 4.4 was the new species of the genus actinomycetes that had the highest level of antibiotic activity showing promising anticancer activity on cervical carcinoma cells and Glioma cells UG- 87.