The Bengamides: A Mini-Review of Natural Sources, Analogues, Biological Properties, Biosynthetic Origins, and Future Prospects

White, Kimberly N.; Tenney, Karen; Crews, Phillip

doi:10.1021/acs.jnatprod.6b00970

Cited by 42 publications

(31 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…LC-MS analysis of the fraction 7 reveals that the sponge has components, mostly alkaloids (N-containing heterocycles: Bengamide Q, 4'-N-methyl-5'-hydroxystaurosporine, and clavepictine A). Those isolated compounds have been reported to have a high anticancer activity [13][14][15]. In regard to mechanism of action, several recent studies reported that alkaloids have the ability to promote apoptosis through inducing DNA damage [16][17][18].…”

Section: In Vitro Mtt Cytotoxic Assay Of Fractionmentioning

confidence: 99%

In Vitro Cytotoxic Anticancer Potential of Bioactive Fraction Isolated From Indonesian Tidal Sponge Calthropella Sp.

Susilowati

Swasono

Okino

et al. 2019

Asian J Pharm Clin Res

View full text Add to dashboard Cite

Objective: This study was taken to examine the cytotoxicity of the bioactive fraction isolated from marine sponge Calthropella sp. as a preliminary anticancer assay and identify its bioactive compounds.Methods: The cytotoxic activity was assessed by 3-(4,5-dimethylthiazol-2-y1)-2,5-diphenyltetrazolium bromide assay against three human cancer cell lines, namely human breast (MCF-7), human lung (H-460), and human liver (HepG-2). The bioactive compounds were identified using a high-resolution liquid chromatography–mass spectroscopy (LC–MS).Results: The active fraction 7 showed moderate to strong cytotoxic activity on all cell lines tested and promising a strong potent cytotoxicity against MCF-7 cell lines with IC50 value as low as 1.925 μg/mL comparable to control, cisplatin (IC50 0.977 μg/mL). In regard to the promising bioactive compounds, the high-resolution LC–MS predicted the existing of several known compounds such as bengamide Q, clavepictine A, 4’-N-methyl-5’- hydroxystaurosporine, carteriofenone A, and one strong possibility of a new compound.Conclusion: This study has revealed that the isolated bioactive fraction of Indonesian tidal sponge, Calthropella sp., possesses potential anticancer properties with a promising significant cytotoxicity on MCF-7 cell lines (IC50 1.925 μg/mL).

show abstract

Section: In Vitro Mtt Cytotoxic Assay Of Fractionmentioning

confidence: 99%

In Vitro Cytotoxic Anticancer Potential of Bioactive Fraction Isolated From Indonesian Tidal Sponge Calthropella Sp.

Susilowati

Swasono

Okino

et al. 2019

Asian J Pharm Clin Res

View full text Add to dashboard Cite

show abstract

“…Moreover, there are tens of reversible inhibitors of both natural and synthetic origin. They include anthranilic acid sulfonamides [ 88 ], bengamides [ 89 ], benzoselnazalones [ 63 ] and compounds based on bestatin [ 90 ], 1,2,4-triazole [ 91 ], and pyrazolo[4,3-b]indole [ 92 ]. Research on new, reversible agents that are safe for organisms is ongoing.…”

Section: Perspective and Conclusionmentioning

confidence: 99%

Neutral metalloaminopeptidases APN and MetAP2 as newly discovered anticancer molecular targets of actinomycin D and its simple analogs

et al. 2018

View full text Add to dashboard Cite

The potent transcription inhibitor Actinomycin D is used with several cancers. Here, we report the discovery that this naturally occurring antibiotic inhibits two human neutral aminopeptidases, the cell-surface alanine aminopeptidase and intracellular methionine aminopeptidase type 2. These metallo-containing exopeptidases participate in tumor cell expansion and motility and are targets for anticancer therapies. We show that the peptide portions of Actinomycin D and Actinomycin X2 are not required for effective inhibition, but the loss of these regions changes the mechanism of interaction. Two structurally less complex Actinomycin D analogs containing the phenoxazone chromophores, Questiomycin A and Actinocin, appear to be competitive inhibitors of both aminopeptidases, with potencies similar to the non-competitive macrocyclic parent compound (Ki in the micromolar range). The mode of action for all four compounds and both enzymes was demonstrated by molecular modeling and docking in the corresponding active sites. This knowledge gives new perspectives to Actinomycin D's action on tumors and suggests new avenues and molecules for medical applications.

show abstract

“…The aim of this study was to determine the level of NF-κB subunits in the resistant HL-60/5-FU cell line and to evaluate the potential of a novel uracil analog U-332 to inhibit activation of NF-κB family members in this cell line. For comparison, bengamide (BGD) [32], a potent inhibitor of NF-κB activation was included in the research.…”

Section: Introductionmentioning

confidence: 99%

New uracil analog U-332 is an inhibitor of NF-κB in 5-fluorouracil-resistant human leukemia HL-60 cell line

Długosz-Pokorska

Pięta

Kędzia

et al. 2020

BMC Pharmacol Toxicol

View full text Add to dashboard Cite

Background: 5-Fluorouracil (5-FU) is an antimetabolite that interferes with DNA synthesis and has been widely used as a chemotherapeutic drug in various types of cancers. However, the development of drug resistance greatly limits its application. Overexpression of ATP-binding cassette (ABC) transporters in many types of cancer is responsible for the reduction of the cellular uptake of various anticancer drugs causing multidrug resistance (MDR), the major obstacle in cancer chemotherapy. Recently, we have obtained a novel synthetic 5-FU analog, U-332 [(R)-3-(4-bromophenyl)-1-ethyl-5-methylidene-6-phenyldihydrouracil], combining a uracil skeleton with an exo-cyclic methylidene group. U-332 was highly cytotoxic for HL-60 cells and showed similar cytotoxicity in the 5-FU resistant subclone (HL-60/5FU), in which this analog almost completely abolished expression of the ATP-binding cassette (ABC) transporter, multidrug resistance associate protein 1 (ABCC1). The expression of ABC transporters is usually correlated with NF-κB activation. The aim of this study was to determine the level of NF-κB subunits in the resistant HL-60/5-FU cells and to evaluate the potential of U-332 to inhibit activation of NF-κB family members in this cell line. Methods: Anti-proliferative activity of compound U-332 was assessed by the MTT assay. In order to disclose the mechanism of U-332 cytotoxicity, quantitative real-time PCR analysis of the NF-κB family genes, c-Rel, RelA, RelB, NF-κB1, and NF-κB2, was investigated. The ability of U-332 to reduce the activity of NF-κB members was studied by ELISA test. Results: In this report it was demonstrated, using RT-PCR and ELISA assay, that members of the NF-κB family c-Rel, RelA, RelB, NF-κB1, and NF-κB2 were all overexpressed in the 5-FU-resistant HL-60/5FU cells and that U-332 potently reduced the activity of c-Rel, RelA and NF-κB1 subunits in this cell line. Conclusions: This finding indicates that c-Rel, RelA and NF-κB1 subunits are responsible for the resistance of HL-60/5FU cells to 5-FU and that U-332 is able to reverse this resistance. U-332 can be viewed as an important lead compound in the search for novel drug candidates that would not cause multidrug resistance in cancer cells.

show abstract

The Bengamides: A Mini-Review of Natural Sources, Analogues, Biological Properties, Biosynthetic Origins, and Future Prospects

Cited by 42 publications

References 65 publications

In Vitro Cytotoxic Anticancer Potential of Bioactive Fraction Isolated From Indonesian Tidal Sponge Calthropella Sp.

In Vitro Cytotoxic Anticancer Potential of Bioactive Fraction Isolated From Indonesian Tidal Sponge Calthropella Sp.

Neutral metalloaminopeptidases APN and MetAP2 as newly discovered anticancer molecular targets of actinomycin D and its simple analogs

New uracil analog U-332 is an inhibitor of NF-κB in 5-fluorouracil-resistant human leukemia HL-60 cell line

Contact Info

Product

Resources

About