1227962-62-0

1,1''-(4,4'',5,5''-Tetrachloro[1,3''-bi-1H-pyrrole]-2,2''-diyl)bis[1-(2-hydroxyphenyl)methanone] is a marine anticancer compound. Also, it possesses anti-bacterial properties against methicillin-resistant Staphylococcus aureus.

ChEBI: (-)-marinopyrrole A is a member of the class of pyrroles that is 1'H-1,3'-bipyrrole substituted by four chloro groups at positions 4, 4', 5 and 5' and two 2-hydroxybenzoyl moieties at positions 2 and 2'. It is isolated from Streptomyces sp.CNQ-418 and exhibits cytotoxic and antibacterial activities. It has a role as an antimicrobial agent, an antibacterial agent, an antineoplastic agent, a marine metabolite and a bacterial metabolite. It is a member of pyrroles, an organochlorine compound, a member of phenols and an aromatic ketone.

marinopyrrole a is a selective inhibitor of mcl-1 with ic50 value of 10.1μm [1].marinopyrrole a is a natural product froma species of marine-derived streptomycetes and is reported to be an antagonist of mcl-1. mcl-1 is a member of the anti-apoptotic bcl-2 family, which is a well-validated drug target for cancer treatment. nmr titration experiments show that marinopyrrole a can directly interact with mcl-1. it can prevent bim-bh3 peptides from binding to mcl-1 but not bcl-xl. the cell based assay shows a high selectivity of marinopyrrole a. treatment with marinopyrrole a inhibit the viability of k562 cells transfected with mcl-1 gene with ec50 value of 1.6μm. the selectivity is more than 40-fold greater over the cells transfected with bcl-xl gene. moreover, marinopyrrole a can decreases mcl-1 expression by increasing the cleavage of caspase-3 and parp. marinopyrrole a is also reported to completely restore the sensitivity of multidrug resistant leukemia cells to abt-737 [1].

The compound (CAS:1227869-61-5) (44 mg, 0.082 mmol, 1.0 eq.) was dissolved in dichloromethane (800 μL) at 0 °C. Subsequently, a dichloromethane solution of 1 M boron tribromide (BBr3) (330 μL, 0.327 mmol, 4.0 equiv) was added dropwise to this solution. The reaction mixture was stirred continuously at 0 °C for 1 hour. Upon completion of the reaction, the reaction was quenched by the addition of saturated aqueous sodium bicarbonate (NaHCO3) solution (2 mL). The reaction mixture was extracted with dichloromethane (2 x 3 mL) and the organic phases were combined and dried over anhydrous magnesium sulfate (MgSO4). After filtration, the organic phase was concentrated to give the crude product. The crude product was purified by fast column chromatography (silica gel, n-hexane:ethyl acetate=9:1) to afford the compound (CAS:1010732-14-5) (37 mg, 0.0733 mmol, 90% yield) as a bright yellow solid. The two block-transfer isomers were further analyzed and separated by chiral high performance liquid chromatography (HPLC): using a Chiralcel OD-H 5 μL column (20×250 mm) with a mobile phase of n-hexane:isopropanol=93:7 at a flow rate of 9 mL/min, (-)-1 and (+)-1 were obtained, respectively.

Mcl-1: 10.1 μM (IC₅₀)

[1] doi k, li r, sung ss, et al. discovery of marinopyrrole a (maritoclax) as a selective mcl-1 antagonist that overcomes abt-737 resistance by binding to and targeting mcl-1 for proteasomal degradation. j biol chem. 2012 mar, 287(13): 10224-35.