Development of a Green Technology Approach to Marine Natural Products Synthesis: Mineral-Based Microbial Amplification System to Make Bryostatins

Isolation, analytical measurements, and cell line studies of the iron–bryostatin-1 complex

“…44 A study by Manning et al 45 Complexing taxol with iron resulted with no GI 50 values less than 10 -8 M. 45 Bryostatin has been continuously tested for its efficacy to treat various forms of cancer, HIV, AD, and stroke side effects although obtaining the compound is costly and technically trying. In this study, iron-bryostatin-1 was produced by a pharmaceutical aquaculture technique followed by an extraction process developed by Manning et al 34 Comparison of the original 13 C and 1 H NMR spectra to those of the iron-bryostatin-1 complex and the illustration of peaks shifting from their relative ranges on the graphs suggests that the presence of iron resulted in structural changes in the binding preference of oxygen atoms found in bryostatin-1. The NCI's 60 cell line panel demonstrated that the medicinal efficacy of iron-bryostatin-1 was on average lower than pure bryostatin-1 by approximately 13 percent.…”

“…The process developed involves a colonization step, an amplification phase, and an extraction step. 34 Variations of bryostatin structures derived from changes induced by environmental chemical conditions were identified using FT-ICR, MALDI-TOF-MS, UV/Vis absorbance spectroscopy, and molecular modeling to improve recognition of bryostatin compounds after the extraction step. 35 Another study by Manning et al 36 using computational methods produced geometric data that indicated iron-bryostatin-1, which naturally binds in the environment, increases water solubility and stabilizes the molecule.…”

“…36 The iron-bryostatin-1 complex described in this study was synthesized using a pharmaceutical aquaculture technique developed from this lab. 34 molecule, bryostatin-1 complexed to iron with four coordination sites occupied by water molecules, and iron complexed to bryostatin-1 with two water molecules and two hydroxides in the inner sphere of the hexavalent complex. 42 Adding iron to the complex lowers the energy, indicating that the metal-ligand complex is more stable than the molecule itself.…”