Pheophytin a 

Pheophytin a is a multi-target inhibitor, anticancer agent, antioxidant and antiviral agent. Pheophytin a directly binds to and inhibits HCV-NS3/4A protease (IC₅₀=0.89 μM) to block viral replication. Pheophytin a also scavenges free radicals, reduces ferric ions, and exhibits cytotoxic activity against breast cancer cells. Pheophytin a effectively inhibits LPS-induced production of nitric oxide, prostaglandin E2, NOS2 and COX-2, as well as various pro-inflammatory cytokines, by downregulating the transcription levels of inflammatory mediators and blocking the ERK1/2 and STAT-1 pathways. In a low nerve growth factor environment, Pheophytin a also enhances ERK1/2 phosphorylation and synergistically promotes neurite outgrowth through MAPK pathway. Pheophytin a can be used to investigate the pathogenic mechanisms of diseases including chronic hepatitis C, sepsis, breast cancer and Alzheimer's disease^{[1][2][3][4][5]}.

At concentrations of 5-25 μM with a 30-min pre-incubation followed by 24 h of LPS stimulation, Pheophytin a exhibits cytotoxicity toward LPS-stimulated RAW 264.7 murine macrophages at 25 μM, but shows no such effect at 5 μM or 10 μM^[1].
Pheophytin a (1-10 μM; pre-incubated for 30 min followed by LPS stimulation for 6 h) reduces LPS-induced NOS2 protein expression in RAW 264.7 mouse macrophages in a dose-dependent manner; when cells are pre-incubated with concentrations of 1, 5, or 10 μM for 30 min, the inhibitory effect at 10 μM is significant, whereas administration after LPS stimulation shows no effect^[1].
Pheophytin a (1-10 μM; pre-incubated for 30 min, followed by LPS stimulation for 3 h) dose-dependently inhibits LPS-induced NOS2 mRNA expression in RAW 264.7 mouse macrophages when pre-incubated at concentrations of 1, 5 or 10 μM for 30 min, and exhibits significant inhibitory effects at all tested concentrations^[1].
Pheophytin a (10 μM; pre-incubated for 30 min, 10-30 min after LPS stimulation) enhances LPS-induced ERK1/2 phosphorylation in RAW 264.7 mouse macrophages when cells are pre-incubated with 10 μM Pheophytin a for 30 min and proteins are harvested at 10, 15 or 30 min after LPS stimulation; its inhibitory effect on LPS-induced NO production is partially reversed by the ERK1/2 inhibitor U0126 (HY-12031A); Pheophytin a has no effect on LPS-induced phosphorylation of JNK, p38 or Akt^[1].
The IC₅₀ values of Pheophytin a microparticles for scavenging superoxide anion radicals and nitric oxide radicals are 200.5 μg/mL and 132.7 μg/mL, respectively; the IC₅₀ value for cytotoxicity against MCF-7 human breast cancer cells is 35.9 μg/mL^[2].
Pheophytin a (0.9-31.2 μg/mL; 48 h) dose-dependently potentiates nerve growth factor-induced neurite outgrowth in PC12 cells; the effect at 3.9 μg/mL is comparable to that of high-concentration nerve growth factor, which enhances the phosphorylation level of ERK1/2 without affecting the total ERK level or the phosphorylation levels of p38 and JNK^[3].
Pheophytin a (100 nM-10 μM; 60 min) inhibits FmLP-induced chemotaxis of human polymorphonuclear leukocytes in a dose-dependent manner^[4].
Pheophytin a (0.1-6 μM; 48-96 h) inhibits the expression of HCV proteins and RNA in HCV subgenomic replicon cells, with an IC₅₀ of 4.97 μM, and exhibits synergistic anti-HCV activity with IFNa-2a^[5].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Pheophytin a (80-800 nmol/20 μl; topical; single application) exhibits a dose-dependent suppressive effect on TPA-induced mouse ear edema, with the 800 nmol dose reducing edema to levels near untreated control mice^[4].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

871.20

C₅₅H₇₄N₄O₅

603-17-8

Solid

Brown to black

COC([C@@H]1/C2=C([C@H]([C@@H]3C)CCC(OC/C=C(C)/CCC[C@H](C)CCC[C@H](C)CCCC(C)C)=O)/N=C3/C=C(C(C)=C/4C=C)\NC4=C/C5=N/C(C(CC)=C5C)=C\C6=C(C)C(C1=O)=C2N6)=O

Room temperature in continental US; may vary elsewhere.

• [1]. Lin CY, et al. Pheophytin a inhibits inflammation via suppression of LPS-induced nitric oxide synthase-2, prostaglandin E2, and interleukin-1β of macrophages. Int J Mol Sci. 2014;15(12):22819-22834. Published 2014 Dec 9.  [Content Brief]

  [2]. Mohammed HA, et al. Formulation of Ethyl Cellulose Microparticles Incorporated Pheophytin A Isolated from Suaeda vermiculata for Antioxidant and Cytotoxic Activities. Molecules. 2019 Apr 17;24(8):1501.  [Content Brief]

  [3]. Ina A, et al. Pheophytin a, a low molecular weight compound found in the marine brown alga Sargassum fulvellum, promotes the differentiation of PC12 cells. Int J Dev Neurosci. 2007;25(1):63-68.  [Content Brief]

  [4]. Okai Y, et al. Potent anti-inflammatory activity of pheophytin a derived from edible green alga, Enteromorpha prolifera (Sujiao-nori). Int J Immunopharmacol. 1997;19(6):355-358.  [Content Brief]

  [5]. Wang SY, et al. Bioactivity-guided screening identifies pheophytin a as a potent anti-hepatitis C virus compound from Lonicera hypoglauca Miq. Biochem Biophys Res Commun. 2009;385(2):230-235.  [Content Brief]