Investigating Alkylated Prodigiosenes and Their Cu(II)‐Dependent Biological Activity: Interactions with DNA, Antimicrobial and Photoinduced Anticancer Activity

Abstract

Prodigiosenes are a family of red pigments with versatile biological activity. Their tripyrrolic core structure has been modified many times in order to manipulate the spectrum of activity. We have been looking systematically at prodigiosenes substituted at the C ring with alkyl chains of different lengths, in order to assess the relevance of this substituent in a context that has not been investigated before for these derivatives: Cu(II) complexation, DNA binding, self-activated DNA cleavage, photoinduced cytotoxicity and antimicrobial activity. Our results indicate that the hydrophobic substituent has a clear influence on the different aspects of their biological activity. The cytotoxicity study of the Cu(II) complexes of these prodigiosenes shows that they exhibit a strong cytotoxic effect towards the tested tumor cell lines. The Cu(II) complex of a prodigiosene lacking any alkyl chain excelled in its photoinduced anticancer activity, thus demonstrating the potential of prodigiosenes and their metal complexes for an application in photodynamic therapy (PDT). Two derivatives along with their Cu(II) complexes showed also antimicrobial activity against Staphylococcus aureus strains.

Synthesis, Structure, Spectral, Electrochemical, and Theoretical Studies of Ru(II) Complexes of 3-Pyrrolyl BODIPY-Based Ligands

“…α-Pyrrolyl dipyrrins having a pyrrolyl group at the α-position of the dipyrrin unit belongs to the family of natural products called prodigiosins , 1 which are open-chain red pigments isolated from microorganisms such as streptomyces and serratia. There are different methods − available for the synthesis of prodigiosin 1 . Interestingly, α-pyrrolyl dipyrrins readily complex with the BF 2 unit to form BF 2 -complex of α-pyrrolyl dipyrrins known as 3-pyrrolyl BODIPYs (BODIPY: 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene) which are highly fluorescent and have been used extensively as biological probes and for other applications. − A few years back, we ,− and others − reported a straightforward synthesis of meso -aryl 3-pyrrolyl BODIPYs 2 and explored their physicochemical properties.…”

“…J = 6.7 Hz, 3H); 13 C NMR (126 MHz, CDCl 3 ) δ 13 C NMR (126 MHz, CDCl 3 ) δ 159.7, 156.1, 151.1, 151.0, 143.8, 143.8, 143.6, 140.8, 140.6, 140.1, 137.2, 134.1, 131.6, 131.0, 130.8, 129.1, 128.5, 127.8, 125.6, 123.5, 123.3, 120.7, 120.6, 120.0, 119.8, 117.8, 117.1, 117.1, 85.6, 83.6, 83.2, 81.1, 30.6, 29.6, 22.7, 21.5, 18.8; 11 B NMR (128 MHz, CDCl 3 ) δ 1.16, 0.92, 0.68; 19 F NMR (376 MHz, CDCl 3 ) δ −130.02, −130.10, −130.18, −130.26, −130.29, −130.37, −130.45, −130.53, −147.36, −147.45, −147.53, −147.61, −147.63, −147.72, −147.80, −147.88; HRMS (ESI-TOF) m/z: [M] + calcd for C 37 H 34 BF 2 N 4 ORu, 701.1838; found 701.1838. Yield: 50% (40 mg); 1 H NMR (400 MHz, DMSO) δ 13.42 (s, 1H), 7.83−7.77 (m, 2H), 7.72 (s, 1H), 7.62 (d, J = 7.5 Hz, 2H), 7.57 (d, J = 7.7 Hz, 1H), 7.44 (d, J = 7.8 Hz, 2H), 7.41−7.30 (m, 3H),7.12 (d, J = 4.5 Hz, 1H), 6.90 (d, J = 3.9 Hz, 1H), 6.70 (d, J = 3.3 Hz, 1H), 6.53 (s, 1H), 5.83 (s, 1H), 5.62 (d, J = 5.3 Hz, 1H), 5.43 (s, 1H), 5.15 (d, J = 5.5 Hz, 1H), 2.46 (s, 3H), 2.19 (s, 1H), 2.10 (s, 3H), 0.82 (d, J = 4.9 Hz, 3H), 0.69 (d, J = 5.4 Hz, 3H);13 C NMR (101 MHz, DMSO) δ 158.1, 151.3, 141.9, 140.5, 139.9, 139.2, 137.5, 136.9, 134.9, 134.6, 133.1, 132.1, 131.8, 131.2, 131.2, 131.1, 129.6, 126.9, 124.6, 123.4, 123.3, 120.9, 120.8, 116.3, 116.3, 116.2, 112.6, 111.3, 86.8, 85.9, 82.7, 82.2, 30.6, 21.9, 21.8, 21.4, 18.7; 11 B NMR (128 MHz, CDCl 3 ) δ 5.96, 5.72, 5.48; 19 F NMR (376 MHz, DMSO) δ −126.13, −126.19, −126.29, −126.39, −126.47, −126.56, −126.63, −149.99, −150.04, −150.13, −150.25, −150.32, −150.41, −150.46; HRMS (ESI-TOF) m/z: [M] + calcd for C 37 H 33 BF 2 N 5 Ru, 698.1835; found 698.1856.…”