prodigiosin and butylcycloheptylprodigiosin

Prodiginines are bacterial red polypyrrole pigments and multifaceted secondary metabolites. These agents have anti-proliferative, immunosuppressive, antimicrobial, and anticancer effects. Recent analysis revealed that prodigiosin hypersensitizes Serratia marcescens to gamma radiation. In the present study, we report the cytotoxicity and genotoxicity properties of undecylprodigiosin and butylcycloheptylprodigiosin in the presence and absence of radiation through the MTT and alkaline comet experiments.. Findings demonstrated that undecylprodigiosin was at least a fivefold more cytotoxic at low radiation doses (1 and 3 Gy) on both MCF7 and HDF lines rather than in the absence or high radiation doses (5 Gy) (P value < 0.05). Although butylcycloheptylprodigiosin toxicity on MCF7 and HDF was dose-dependent, it was not influenced by any radiation doses (P value > 0.05). Comet findings confirmed that these compounds' genotoxicity is only dose-dependent. Radiation had no significant effects on DNA damage on any of the cells (P value > 0.05).. In general, it can be concluded that the prodiginines are cytotoxic agents that act as a double-edged sword, radiosensitizers and radio-protective, respectively at low and high radiation doses in cancer treatment process. As the results they could be used in antitumor therapies very soon.

Topics: Anti-Infective Agents; Antineoplastic Agents; Cell Line; DNA Damage; Humans; Immunosuppressive Agents; MCF-7 Cells; Neoplasms; Photosensitizing Agents; Prodigiosin

Ion mobility spectrometry was utilized to corroborate the identity of streptorubin B (

Topics: Biological Products; Ion Mobility Spectrometry; Molecular Structure; Prodigiosin; Streptomyces coelicolor

The search for new chemotherapeutics unaffected by efflux pumps would significantly increase life expectancy in patients with malignant cancers. In this study, butylcycloheptylprodigiosin and undecylprodigiosin were HPLC-purified and verified, using nuclear magnetic resonance spectroscopy. Cell cytotoxicity and transportation kinetics on multiple-drug resistance (MDR) cells were evaluated. Daunorubicin and butylcycloheptylprodigiosin were less toxic in the MDR1 overexpressing line, but undecylprodigiosin revealed potent toxicity toward MDR1 and BCRP expressing malignant cells. There was no noticeable change in MDR1 and BCRP transcripts during 3 days of treatment with prodiginines. While daunorubicin and mitoxantrone uptake from the cell environment significantly decreased with increasing multidrug resistance up to 46% and 62%, respectively, the accumulation of undecylprodigiosin and to a lesser extent butylcycloheptylprodigiosin in the resistance cells occurred cell- and dose-dependently via a passive diffusion process and were almost equally sensitive to the parent lines. The efflux of xenobiotics commenced immediately with different kinetics in various cells. A greater amount of daunorubicin and mitoxantrone were rapidly thrown out of their corresponding MDR cells in the absence of the specific inhibitor (3.01 and 1.81 dF/min, respectively) and represented functional efflux pumps. MDR pumps did not apparently influence undecylprodigiosin efflux patterns; but butylcycloheptylprodigiosin was partially removed from EPG85.257RDB cells at the rate of 2.66 and 1.41 dF/min in the absence and presence of verapamil, respectively.

Topics: Antineoplastic Agents; ATP Binding Cassette Transporter, Subfamily B, Member 1; ATP Binding Cassette Transporter, Subfamily G, Member 2; Cell Line, Tumor; Cell Survival; Dose-Response Relationship, Drug; Drug Resistance, Multiple; Humans; MCF-7 Cells; Molecular Structure; Neoplasm Proteins; Neoplasms; Prodigiosin; Streptomyces

The cyclic prodigiosins are an important family of bioactive natural products that continue to be the subject of numerous structural, synthetic, and biosynthetic studies. In particular, the structural assignments of the isomeric cyclic prodigiosins butylcycloheptylprodigiosin (BCHP) and streptorubin B have been the cause of significant confusion. Herein, we report detailed studies regarding the electron impact (EI) mass spectra of synthetic BCHP and streptorubin B that have allowed us to distinguish the two compounds in the absence of quality historical isolation NMR data. On the basis of these fragmentation differences, the status of BCHP as a natural product is challenged. The proposed mechanism of fragmentation is supported by the EI mass spectra of synthetic pentyl-chain analogues of BCHP and streptorubin B, X-ray crystallography, and DFT calculations. Elimination of BCHP from the prodigiosin family supports a proposed evolutionary hypothesis for the surprising biosynthesis of cyclic prodigiosins.

Topics: Biological Products; Crystallography, X-Ray; Molecular Conformation; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Prodigiosin

Conflicting reports are found in the literature on whether the ortho-pyrrolophane derivative 6, which has been named "butylcycloheptylprodigiosin" even though it is a cyclononane derivative, is a natural product or merely a mis-assigned structure. This dispute has now been resolved by an unambiguous total synthesis of this complex alkaloid which confirms the initial structure assignment. The chosen approach is largely catalysis-based, featuring the first application of a "Narasaka-Heck" reaction in natural product chemistry. This palladium-catalyzed transformation allows the unsaturated oxime ester 26 to be converted into the bicyclic dihydropyrrole 27. Other notable reactions of the reported approach to 6 are a regioselective Tsuji-Trost reaction of the doubly allylic acetate 21 with methyl acetoacetate, a base-induced aromatization of 27 to the corresponding pyrrole 28, a chemoselective oxidation of the benzylic methyl group in 33 with cerium ammonium nitrate in a biphasic reaction medium that does not affect the labile pyrrole nucleus, and a Suzuki cross-coupling for the completion of the heterocyclic domain. Diversification in the latter step leads to a set of analogues that differ from the natural product in the terminal (hetero)arene ring. This structural modification results in complete loss of the very pronounced ability of the parent compound 6 to induce oxidative cleavage in double stranded DNA in the presence of Cu(II). Several cyclononane-, cyclononene- and cyclononadiene derivatives prepared en route to 6 have been characterized by crystal structure analysis, allowing the conformational behavior of nine-membered carbocycles to be studied.

Topics: Biochemistry; Crystallography, X-Ray; DNA; Molecular Structure; Prodigiosin

A short and efficient total synthesis of the tripyrrole alkaloid butylcycloheptylprodigiosin is described. Key to the brevity of the approach is a two-step synthesis of macrocyclic formylpyrrole 4 from cyclononenone 6.

Topics: Formates; Hydrolysis; Hydroxylation; Ketones; Molecular Structure; Prodigiosin

Topics: Esters; Molecular Structure; Phantoms, Imaging; Prodigiosin; Pyrroles