A water-soluble iron-porphyrin complex capable of rescuing CO-poisoned red blood cells.

We describe herein a small-molecule platform that exhibits key properties needed by an antidote for CO poisoning. The design features an iron-porphyrin complex with bulky substituents above and below the macrocyclic plane to provide a hydrophobic pocket for CO binding and to prevent the formation of inactive oxo-bridged dimers. Peripheral charged groups impart water solubility. We demonstrate that the Fe(II) complex of a porphyrin with 2,6-diphenyl-4-sulfophenyl meso substituents can bind CO, stoichiometrically sequester CO from carboxyhemoglobin, and rescue CO-poisoned red blood cells.

Gold(III) porphyrins: Synthesis and interaction with G-quadruplex DNA.

G-quadruplex nucleic acids (G4s) are RNA and DNA secondary structures involved in the regulation of multiple key biological processes. They can be found in telomeres, oncogene promoters, RNAs, but also in viral genomes. Due to their unique structural features, very distinct from the canonical duplexes or single-strands, G4s represent promising pharmacological targets for small molecules, namely G4-ligands. Gold(III) penta-cationic porphyrins, as specific G4 ligands, are able to inhibit HIV-1 infectivity and their antiviral activity correlates with their affinity for G4s. Up to now, one of the best antiviral compounds is meso-5,10,15,20-tetrakis[4-(N-methyl-pyridinium-2-yl)phenyl]porphyrinato gold(III) (1). Starting from this compound, we report a structure/affinity relationship study of gold(III) cationic porphyrins to find out the best porphyrin candidate for functionalization, in order to study the antiviral mechanism of action of these gold(III) porphyrins.

In Vitro Anti-Leishmanial Effect of Metallic Meso-Substituted Porphyrin Derivatives against Leishmania braziliensis and Leishmania panamensis Promastigotes Properties.

In this study, a family of porphyrins based on 5,10,15,20-Tetrakis(4-ethylphenyl)porphyrin (1, Ph) and six metallo-derivatives (Zn2+(2, Ph-Zn), Sn4+(3, Ph-Sn), Mn2+ (4, Ph-Mn), Ni2+ (5, Ph-Ni), Al3+ (6, Ph-Al), and V3+ (7, Ph-V)) were tested as photosensitizers for photodynamic therapy against Leishmania braziliensis and panamensis. The singlet oxygen quantum yield value (ΦΔ) for (1-7) was measured using 1,3-diphenylisobenzofuran (DPBF) as a singlet oxygen trapping agent and 5,10,15,20-(tetraphenyl)-porphyrin (H2TPP) as a reference standard; besides, parasite viability was estimated by the MTT assay. After metal insertion into the porphyrin core, the ΦΔ increased from 0.76-0.90 and cell viability changed considerably. The ΦΔ and metal type changed the cytotoxic activity. Finally, (2) showed both the highest ΦΔ (0.90) and the best photodynamic activity against the parasites studied (IC50 of 1.2 µM).

Comparative in†vitro Studies of the Topoisomerase I Inhibition and Anticancer Activities of Metallated N-Confused Porphyrins and Metallated Porphyrins.

Using the original approach, a series of metallated N-confused porphyrins and metallated porphyrins have been synthesized and characterized. For all the synthesized porphyrins, in vitro studies of cytotoxic activity against K562, U937, HL-60, Jurkat, A549 and HeLa cancer cell lines, the ability to induce apoptosis and effects on the cell cycle as well as the kinetics of proliferative activity of porphyrins and their respective metallated complexes in real time have been developed. The inhibitory activity of metallated porphyrins against human topoisomerase I and the possible mechanism of inhibition have been carried out by modelling using molecular docking.

S-seco-porphyrazine as a new member of the seco-porphyrazine family - Synthesis, characterization and photocytotoxicity against cancer cells.

An important subgroup within the porphyrazine (Pz) family constitutes seco-porphyrazines, in the chemical structure of which one pyrrole unit is opened in the oxidative process. So far, there are only limited data on N-seco- and C-seco-Pzs. Here, the synthesis of a novel member of the Pzs seco-family, represented by an S-seco-tribenzoporphyrazine analogue, 22,23-bis(4-(3,5-dibutoxycarbonylphenoxy)butylsulfanyl)tribenzo[b,g,l]-22,23-dioxo-22,23-seco-porphyrazinato magnesium(II), is reported, with moderate 34% yield. The new derivative was characterized using NMR spectroscopy, UV-Vis spectroscopy, and mass spectrometry. In the photochemical study performed following the indirect chemical method with 1,3-diphenylisobenzofuran, S-seco-Pz revealed a high singlet oxygen quantum yield of 0.27 in DMF. Potential photocytotoxicity of S-seco-Pz was assessed in vitro on three cancer cell lines - two oral squamous cell carcinoma cell lines derived from the tongue (CAL 27, HSC-3) and human cervical epithelial adenocarcinoma cells (HeLa). In the biological study, the macrocycle was tested in its free form and after loading into liposomes. It is worth noting that S-seco-Pz was found to be non-toxic in the dark, with cell viability levels over 80%. The photocytotoxic IC50 values for free S-seco-Pz were 0.61, 0.18, and 4.1 µM for CAL 27, HSC-3 and HeLa cells, respectively. Four different liposomal compositions were analyzed, and the cationic liposomes revealed the highest photokilling efficacy, with the IC50 values for CAL 27, HSC-3, and HeLa cells at 0.24, 0.25, and 0.31 µM, respectively. The results of the photocytotoxicity study indicate that the new S-seco-tribenzoporphyrazine can be considered as a potential photosensitizer in photodynamic therapy of cancer, along with the developed cationic liposomal nanocarrier.

Acid-sensitive ROS-triggered dextran-based drug delivery system for advanced chemo-photodynamic synergistic therapy.

In order to improve the treatment efficacy and reduce the side effects, the synergistic therapy has been effectively exploited in cancer treatment. Herein, we fabricated a kind of acid-sensitive ROS-triggered dextran-based drug delivery system (DHTD/Zn-TPP) for synergistic therapy, in which chemotherapeutics doxorubicin was conjugated to the dextran backbone via ROS cleavable thioketal conjugates while photosensitizer porphyrin (Zn-TPP) was encapsulated via acid-responsive metallic coordinated interaction. The structure and acid-responsive self-assemble behavior of DHTD/Zn-TPP were measured by 1 H NMR, Fourier transform infrared, dynamic laser scattering, and transmission electron microscopy. Further, the in vivo ROS-triggered DOX release and anticancer efficiency were evaluated toward HeLa cells and MCF-7 cells. All the data obtained verified that DHTD/Zn-TPP had a significantly improved cell growth inhibitory effect with light irritation due to the combined application of photodynamic-chemotherapy.

In Vivo Photoacoustic Lifetime Based Oxygen Imaging with Tumor Targeted G2 Polyacrylamide Nanosonophores.

Lifetime imaging methods using phosphorescence quenching by oxygen for molecular oxygen concentration measurement have been developed and used for noninvasive oxygen monitoring. This study reports photoacoustic (PA) oxygen imaging powered by polyacrylamide (PAAm) hydrogel nanoparticles (NP) which offer advantages including improved biocompatibility, reduced toxicity, and active tumor targeting. A known oxygen indicator, oxyphor G2, was conjugated with the matrix of the NPs, giving G2-PAA NPs, followed by PEGylation for biocompatibility and F3 surface modification for tumor targeting. Using two lasers providing pump and probe pulses, respectively, PA imaging was performed so as to quantitatively map the oxygen concentration in biological tissues in vivo, including cancer tumors and normal thigh muscles. Furthermore, via the imaging at the pump wavelength and two additional wavelengths, the accumulation of the G2-PAA NPs in the tumors were also determined. The successful imaging experiment accomplished on animal models renders a method for in vivo noninvasive imaging and assessment of hypoxic tumor microenvironments, which is critical for assessing cancer progression, metastasis, and treatment.

A small-sized and stable 2D metal-organic framework: a functional nanoplatform for effective photodynamic therapy.

The efficiency of photosensitizers in tumor photodynamic therapy (PDT) often compromises their poor water solubility, low extinction coefficients, photobleaching, and dissatisfactory reactive oxygen species (ROS) generation efficiency. Herein, a nanoscale 2D metal-organic framework, Sm-H2TCPP nanosheets, was first synthesized by Sm3+-driven coordination with a porphyrin derivative (tetrakis(4-carboxyphenyl)porphyrin (H2TCPP)) for highly effective PDT of breast cancer. The prepared Sm-H2TCPP possessed nanoplate morphology with ultrathin thickness at the sub-10 nm level and an ultrasmall plane size at the sub-100 nm level. Compared with free H2TCPP, the prominent ROS generation capacity of the well-defined Sm-H2TCPP nanosheets is mainly attributed to their improved physicochemical properties and the enhanced intersystem crossing caused by heavy Sm nodes. The significantly improved PDT efficacy of the Sm-H2TCPP nanosheets was further investigated in vitro and in vivo based on the MCF-7 breast cancer model. It is envisaged that the Sm-H2TCPP nanosheets will offer a new avenue for the development of a new class of potential PDT agents.

Red-Emitting Fluorescence Sensors for Metal Cations: The Role of Counteranions and Sensing of SCN- in Biological Materials.

The spatiotemporal sensing of specific cationic and anionic species is crucial for understanding the processes occurring in living systems. Herein, we developed new fluorescence sensors derived from tetrapyrazinoporphyrazines (TPyzPzs) with a recognition moiety that consists of an aza-crown and supporting substituents. Their sensitivity and selectivity were compared by fluorescence titration experiments with the properties of known TPyzPzs (with either one aza-crown moiety or two of these moieties in a tweezer arrangement). Method of standard addition was employed for analyte quantification in saliva. For K+ recognition, the new derivatives had comparable or larger association constants with larger fluorescence enhancement factors compared to that with one aza-crown. Their fluorescence quantum yields in the ON state were 18× higher than that of TPyzPzs with a tweezer arrangement. Importantly, the sensitivity toward cations was strongly dependent on counteranions and increased as follows: NO3- < Br- < CF3SO3- < ClO4- ≪ SCN-. This trend resembles the chaotropic ability expressed by the Hofmeister series. The high selectivity toward KSCN was explained by synergic association of both K+ and SCN- with TPyzPz sensors. The sensing of SCN- was further exploited in a proof of concept study to quantify SCN- levels in the saliva of a smoker and to demonstrate the sensing ability of TPyzPzs under in vitro conditions.

Dual activity of amphiphilic Zn(II) nitroporphyrin derivatives as HIV-1 entry inhibitors and in cancer photodynamic therapy.

Two Zn(II) nitro porphyrin derivatives bearing combinations of meso-4-nitrophenyl and meso-4-methylpyridinium moieties and their free-base precursors were synthesized through one-pot microwave process, purified and characterized. The biological activity of these nitroporphyrins was assessed under both photodynamic and non-photodynamic conditions to correlate their structure-activity relationship (SAR). Unlike, the free-base precursors, Zn(II) complexes of these nitroporphyrins displayed nearly complete inhibition in the entry of lentiviruses such as HIV-1 and SIVmac under non-photodynamic conditions. In addition, the Zn(II) complexes also exhibited a higher in vitro photodynamic activity towards human lung cancer cell-line A549 than their free-base precursors. Our results strongly suggest that incorporation of Zn(II) has improved the antiviral and anticancer properties of the nitroporphyrins. To the best of our knowledge, this is the first report demonstrating the dual activity of nitroporphyrin-zinc complexes as antiviral and anti-cancer, which will aid in their development as therapeutics in clinics.

Porphyrinic Probe for Fluorescence "Turn-On" Monitoring of Cu+ in Aqueous Buffer and Mitochondria.

A zinc(II) porphyrin derivative (ZPSN) was designed and synthesized, and this probe exhibited rapid, selective and reversible binding to Cu+ for fluorescence monitoring in pure aqueous buffer. The detection mechanism is based on Cu+-activated disruption of axial coordination between the pyridyl ligand and the zinc center, which changes the molecular geometry and inhibits intramolecular electron transfer (ET), leading to fluorescence enhancement of the probe. The proposed sensing mechanism was supported by UV-vis spectroscopy/fluorescence spectral titration, NMR spectroscopy, mass spectrometry, and time-resolved fluorescence decay studies. The dissociation constant was calculated to be 6.53 × 10-11 M. CLSM analysis strongly suggested that ZPSN could penetrate live cells and successfully visualize Cu+ in mitochondria. This strategy may establish a design and offer a potential building block for construction of other metal sensors based on a similar mechanism.

Induction of Enzyme-like Peroxidase Activity in an Iron Porphyrin Complex Using Second Sphere Interactions.

Emulating enzymatic reactivity using small molecules has been a long-time challenging pursuit of the scientific community. Peroxidases, ubiquitous heme enzymes that are involved in hormone synthesis and the immune system, have been a prime target of such efforts due to their tremendous potential in the chemical industry as well as in wastewater treatment. Here it is demonstrated that inclusion of a second sphere guanidine moiety in an iron porphyrin not only makes this small molecule a veritable peroxidase catalyst but also offers an auxiliary binding site for organic substrates, facilitating their rapid oxidation with a green oxidant like H2O2. This small molecule analogue exhibits a "ping-pong" mechanism and Michaelis-Menten type kinetics, which is generally typical of metallo-enzymes and follows a mechanism of the natural enzyme in its entirety, including the formation of compound I as the primary oxidant.

Tetra-2,3-pyrazinoporphyrazines with Peripherally Appended Pyridine Rings. 19. Pentanuclear Octa(2-pyridyl)tetrapyrazinoporphyrazines Carrying Externally Carboranthiolate Groups: Physicochemical Properties and Potentialities as Anticancer Drugs.

New pentanuclear porphyrazine complexes of formula [{Pd(CBT)2}4LM]· xH2O (L = tetrakis-2,3-[5,6-di(2-pyridyl)pyrazino]porphyrazinato anion, CBT = m-carborane-1-thiolate, and M = MgII(H2O), ZnII, PdII) were prepared in good yield as dark green hydrated amorphous solids by reaction of the respective pentanuclear species [(PdCl2)4LM] with m-carboran-1-thiol in CH3CN. Physicochemical characterization of the new species was carried out by elemental and thermogravimetric analysis along with IR and 1H/13C NMR measurements. UV-vis spectral characterization performed in DMSO, DMF, and pyridine solution provided information about the stability of the new homo/heteropentanuclear species and their tendency to undergo detachment of the peripheral Pd(CBT)2 groups. The data from NMR, UV-vis, and electrochemical experiments indicate that external coordination of the Pd(CBT)2 units to the mononuclear [LM] species affects only slightly the π electron distribution within the internal macrocyclic choromophore. The Pd(CBT)2 units are released in pyridine solution and in the case of the ZnII complex [{Pd(CBT)2}4LZn] give rise to a finely crystalline light-yellow solid identified by single-crystal X-ray work as the trans isomer of the bispyridine adduct [py2(CBT)2Pd]. The new pentanuclear macrocyclic complexes behave in DMF solution as active photosensitizers for singlet oxygen production, 1O2, the cytotoxic agent in anticancer photodynamic therapy, and have larger quantum yield values (ΦΔ = 0.6-0.7) than those found on average for the related tetrapyrazinoporphyrazine analogs (ΦΔ = 0.4-0.6). The presence of the CBT groups in the currently investigated complexes opens up the possibility for their use in boron neutron capture therapy, leading potentially to new bimodal anticancer curative drugs.

Synthetic Iron Porphyrins for Probing the Differences in the Electronic Structures of Heme a3, Heme d, and Heme d1.

A variety of heme derivatives are pervasive in nature, having different architectures that are complementary to their function. Herein, we report the synthesis of a series of iron porphyrinoids, which bear electron-withdrawing groups and/or are saturated at the ß-pyrrolic position, mimicking the structural variation of naturally occurring hemes. The effects of the aforementioned factors were systematically studied using a combination of electrochemistry, spectroscopy, and theoretical calculations with the carbon monoxide (CO) and nitric oxide (NO) adducts of these iron porphyinoids. The reduction potentials of iron porphyrinoids vary over several hundreds of millivolts, and the X-O (X = C, N) vibrations of the adducts vary over 10-15 cm-1. Density functional theory calculations indicate that the presence of electron-withdrawing groups and saturation of the pyrrole ring lowers the π*-acceptor orbital energies of the macrocycle, which, in turn, attenuates the bonding of iron to CO and NO. A hypothesis has been presented as to why cytochrome c containing nitrite reductases and cytochrome cd1 containing nitrite reductases follow different mechanistic pathways of nitrite reduction. This study also helps to rationalize the choice of heme a3 and not the most abundant heme b cofactor in cytochrome c oxidase.

One-Pot Synthetic Approach toward Porphyrinatozinc and Heavy-Atom Involved Zr-NMOF and Its Application in Photodynamic Therapy.

Herein, we report an iodine-attached Zn(II)-porphyrinic dicarboxylic building block (ZnDTPP-I2-2H, 1) that can be introduced into UiO-66 NMOF via one-pot synthetic approach to generate a new ZnDTPP-I2 doped UiO-66 type nano metal-organic framework (NMOF) of ZnDTPP-I2⊂UiO-66 (2). Compared to its homologous iodine-free NMOF of ZnDTPP⊂UiO-66 (4), ZnDTPP-I2⊂UiO-66 (2) with heavy iodine atoms is a more effective nanosized photosensitizer for singlet oxygen generation under physiological conditions. As expected, 2 displayed a high photodynamic therapy efficacy for treatment of liver cancer cells in vitro.

In vitro anticancer activity of new gold(III) porphyrin complexes in colon cancer cells.

Colorectal cancer (CRC) is the third most common cancer diagnosed worldwide. The limitations of cisplatin-based chemotherapy have prompted intense interest among scientists to search for alternative metal-based anticancer medicines. Gold(III) complexes have been among the most widely investigated since they showed higher cytotoxicity than cisplatin and promising in vitro and in vivo anticancer activities in CRC but their clinical usefulness has been limited by their poor stability under physiological conditions. A novel gold(III) porphyrin complexes [gold(III) porphyrin-adamantane chloride (SN1) and gold(III) porphyrin mono-acetate chloride (SN2)] with improved aqueous stability were synthesized. SN1 and SN2 reduced the survival of human CRC HT-29 and HCT-116 cell lines, caused cell cycle arrest in G2/M phase, and we observed downregulation of the expression of cyclin B1 and cyclin-dependent kinase 1 (Cdk1) along with up-regulation of the active form of p53, p21 and Bcl-2-associated X (Bax). Furthermore, SN1 and SN2 induced apoptosis by the intrinsic pathway, since they lead to the cleavage of caspase 9, caspase 3 and poly(ADP-ribose) polymerase (PARP), and up-regulating Bax. Phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt), nuclear factor-κB (NF-κB) and extracellular signal-regulated kinases (ERK) are important for cell survival and proliferation. SN1 and SN2 lead to decrease in the activity of Akt where the phosphorylated form decreased with time as well as they caused an important decrease in the phosphorylation of ERK and activity of NF-κB. Finally, SN1 and SN2 complexes affected p38/mitogen-activated protein kinase (MAPK) pathway then we recorded an increase in the cyclooxygenase-2 expression and its enzymatic product prostaglandin E2.

Syntheses and CO2 reduction activities of π-expanded/extended iron porphyrin complexes.

The construction of molecular catalysts that are active toward CO2 reduction is of great significance for designing sustainable energy conversion systems. In this study, we aimed to develop catalysts for CO2 reduction by introducing aromatic substituents to the meso-positions of iron porphyrin complexes. Three novel iron porphyrin complexes with π-expanded substituents (5,10,15,20-tetrakis(pyren-1-yl)porphyrinato iron(III) chloride (Fe-Py)), π-extended substituents (5,10,15,20-tetrakis((1,1'-biphenyl)-4-yl)porphyrinato iron(III) chloride (Fe-PPh)) and π-expanded and extended substituents (5,10,15,20-tetrakis(4-(pyren-1-yl)phenyl)porphyrinato iron(III) chloride (Fe-PPy)) were successfully synthesized, and their physical properties were investigated by UV-vis absorption spectroscopy and electrochemical measurements under Ar in comparison with an iron complex with a basic framework, 5,10,15,20-tetrakis(phenyl)porphyrinato iron(III) chloride (Fe-Ph). Moreover, the catalytic activity of the complexes was studied by electrochemical measurements under CO2, and it is found that the complex with the π-expanded substituents exhibits the highest activity among these complexes.

Metalloporphyrin-Encapsulated Biodegradable Nanosystems for Highly Efficient Magnetic Resonance Imaging-Guided Sonodynamic Cancer Therapy.

Traditional photodynamic therapy (PDT) suffers from the critical issues of low tissue-penetrating depth of light and potential phototoxicity, which are expected to be solved by developing new dynamic therapy-based therapeutic modalities such as sonodynamic therapy (SDT). In this work, we report on the design/fabrication of a high-performance multifunctional nanoparticulate sonosensitizer for efficient in vivo magnetic resonance imaging (MRI)-guided SDT against cancer. The developed approach takes the structural and compositional features of mesoporous organosilica-based nanosystems for the fabrication of sonosensitizers with intriguing theranostic performance. The well-defined mesoporosity facilitates the high loading of organic sonosensitizers (protoporphyrin, PpIX) and further chelating of paramagnetic transitional metal Mn ions based on metalloporphyrin chemistry (MnPpIX). The mesoporous structure of large surface area also maximizes the accessibility of water molecules to the encapsulated paramagnetic Mn ions, endowing the composite sonosensitizers with markedly high MRI performance (r1 = 9.43 mM-1 s-2) for SDT guidance and monitoring. Importantly, the developed multifunctional sonosensitizers (HMONs-MnPpIX-PEG) with controllable biodegradation behavior and high biocompatibility show distinctively high SDT efficiency for inducing the cancer-cell death in vitro and suppressing the tumor growth in vivo. This report provides a paradigm that nanotechnology-enhanced SDT based on elaborately designed high-performance multifunctional sonosensitizers will pave a new way for efficient cancer treatment by fully taking the advantages (noninvasiveness, convenience, cost-effectiveness, etc.) of ultrasound therapy and quickly developing nanomedicine.

Tetra(3,4-pyrido)porphyrazines Caught in the Cationic Cage: Toward Nanomolar Active Photosensitizers.

Investigation of a series of tetra(3,4-pyrido)porphyrazines (TPyPzs) substituted with hydrophilic substituents revealed important structure-activity relationships for their use in photodynamic therapy (PDT). Among them, a cationic TPyPz derivative with total of 12 cationic charges above, below and in the plane of the core featured a unique spatial arrangement that caught the hydrophobic core in a cage, thereby protecting it fully from aggregation in water. This derivative exhibited exceptionally effective photodynamic activity on a number of tumor cell lines (HeLa, SK-MEL-28, A549, MCF-7) with effective concentrations (EC50) typically below 5 nM, at least an order of magnitude better than the EC50 values obtained for the clinically approved photosensitizers verteporfin, temoporfin, protoporphyrin IX, and trisulfonated hydroxyaluminum phthalocyanine. Its very low dark toxicity (TC50 > 400 µM) and high ability to induce photodamage to endothelial cells (EA.hy926) without preincubation suggest the high potential of this cationic TPyPz derivative in vascular-targeted PDT.

Synthesis and photodynamic activity of unsymmetrical A3B tetraarylporphyrins functionalized with l-glutamate and their Zn(II) and Cu(II) metal complex derivatives.

Four novel unsymmetrical A3B porphyrins 1, 2, 3 and 4 were synthesized following Lindsey procedure. Porphyrins 3 and 4 include one and three l-glutamate groups, respectively, and all porphyrins were metallated with Zn(II) (1a-4a) or Cu(II) (1b-4b). Porphyrins and metalloporphyrins presented values of singlet oxygen quantum yields (ΦD) ranging from 0.21 to 0.67. The tetraaryl derivatives in this study showed phototoxicity in SiHa cells with IC50 values ranging from <0.01 to 6.56±0.11µM, the metalloporphyrin 4a showed the lowest IC50 value. Comparing the phototoxic activity between all porphyrins, functionalization of porphyrins with glutamate increased 100 times phototoxic activity (1 (IC50 4.81±0.34µM) vs. 3 (IC50 0.04±0.02µM) and 2 (IC50 5.19±0.42µM) vs. 4 (IC50 0.05±0.01µM)). This increased activity could be attributed to reduced hydrophobicity and increased ΦΔ, given by functionalization with l-glutamate. Metalloporphyrins 3a (IC50 0.04±0.01µM) and 4a (IC50<0.01µM) presented the best values ​​of phototoxic activity. Therefore, functionalization and zinc metalation increased the phototoxic activity. SiHa cells treated with porphyrins 3, 4, 3a and 4a at a final concentration of 10µM, showed increased activity of caspase-3 enzyme compared to the negative control; indicating the induction of apoptosis. Differential gene expression pattern in SiHa cells was determined; treatments with metalloporphyrins 4a and 4b were performed, respectively, comparing the expression with untreated control. Treatments in both cases showed similar gene expression pattern in upregulated genes, since they share about 25 biological pathways and a large number of genes. According to the new photophysical properties related to the structural improvement and phototoxic activity, these molecules may have the potential application as photosensitizers in the photodynamic therapy.