Chagas Mariane B, Pontes Daniel O B, Albino Allan V D, Ferreira Emanuel J, Alves Jovelina S F, Paiva Anallicy S, Pontes Daniel L, Langansser Silvana M Z, Ferreira Leandro S
Pharmacy Department, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, 59012-570, Brazil.
Institute of Chemistry, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, 59072-970, Brazil.
Rapid Commun Mass Spectrom. 2020 Sep;34 Suppl 3:e8757. doi: 10.1002/rcm.8757. Epub 2020 Apr 7.
Orientin and isoorientin are C-glycosidic flavonoids, considered as markers of some plant species such as Passiflora edulis var. flavicarpa Degener, and reported in the literature to have pharmacological properties. In order to evaluate and characterize the in vitro metabolism of these flavonoids, phase I biotransformation reactions were simulated using Salen complexes.
These flavonoids were oxidized separately in biomimetic reactions in different proportions, using one oxidant, m-chloroperbenzoic acid or iodosylbenzene, and one catalyst, the Jacobsen catalyst or [Mn(3-MeOSalen)Cl]. The [Mn(3-MeOSalen)Cl] catalyst was synthesized and characterized using spectrometric techniques. The oxidation potentials of the catalysts were compared. All reactions were monitored and analyzed using ultrahigh-performance liquid chromatography diode-array detection (UHPLC-DAD) and high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS).
The analysis by UHPLC-DAD and HPLC/MS/MS showed that isoorientin produces more products than orientin and that [Mn(3-MeOSalen)Cl] produces more products than the Jacobsen catalyst. In addition, [Mn(3-MeOSalen)Cl], which has a higher oxidation potential, formed products with the addition of one or two atoms of oxygen, while the Jacobsen catalyst formed compounds with only one added oxygen atom. The products with the addition of one oxygen atom were mainly epoxides, while those with two added oxygens formed an epoxide in the C-ring and incorporated the other oxygen into the glycosidic moiety.
The formation of epoxides is common in biomimetic reactions and they may represent a safety risk in medicinal products due to their high reactivity. This study may serve as a basis for subsequent pharmacological and toxicological studies that investigate the presence of these compounds as phase I metabolites, and ensure the safe use of plant products containing orientin as a chemical marker.
异荭草素和荭草素是C-糖苷类黄酮，被认为是某些植物物种（如黄果西番莲）的标志物，并且文献报道它们具有药理特性。为了评估和表征这些黄酮类化合物的体外代谢，使用Salen配合物模拟I相生物转化反应。
这些黄酮类化合物在仿生反应中分别以不同比例被氧化，使用一种氧化剂（间氯过苯甲酸或亚碘酰苯）和一种催化剂（雅各布森催化剂或[Mn(3-甲氧基Salen)Cl]）。[Mn(3-甲氧基Salen)Cl]催化剂通过光谱技术进行合成和表征。比较了催化剂的氧化电位。所有反应均使用超高效液相色谱二极管阵列检测（UHPLC-DAD）和高效液相色谱/串联质谱（HPLC/MS/MS）进行监测和分析。
UHPLC-DAD和HPLC/MS/MS分析表明，异荭草素产生的产物比荭草素多，并且[Mn(3-甲氧基Salen)Cl]产生的产物比雅各布森催化剂多。此外，具有较高氧化电位的[Mn(3-甲氧基Salen)Cl]形成了添加一个或两个氧原子的产物，而雅各布森催化剂形成的化合物仅添加了一个氧原子。添加一个氧原子的产物主要是环氧化物，而添加两个氧原子的产物在C环中形成一个环氧化物，并将另一个氧原子并入糖苷部分。
环氧化物的形成在仿生反应中很常见，并且由于其高反应性，它们可能在药品中代表安全风险。本研究可为后续药理和毒理学研究提供基础，这些研究调查这些化合物作为I相代谢物的存在情况，并确保安全使用以荭草素作为化学标志物的植物产品。
